# US 2020/0399376 A1 · Dosing for treatment with anti-tigit and anti-pd-l1 antagonist antibodies

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- Number: US 2020/0399376 A1
- Document ID: US20200399376A1
- Status: Published application
- Kind: A1
- Application number: 16/975,549
- Filed: 2019-02-26
- Published: 2020-12-24
- Earliest claimed: 2018-02-26
- Assignees: Genentech, Inc.
- Applicants: Genentech, Inc.
- Inventors: Raymond D. MENG; Sean Keith KELLEY; Namrata Srivastava PATIL
- Web page: https://patentgrep.com/patent/US20200399376A1

## CPC

- C07K 16/2827: {against B7 molecules, e.g. CD80, CD86}
- A61P 35/00: Antineoplastic agents
- C12N 15/1096: {cDNA Synthesis; Subtracted cDNA library construction, e.g. RT, RT-PCR}
- C12Q 1/6825: Nucleic acid detection involving sensors
- G01N 33/5005: {involving human or animal cells (immunoassay G01N33/56966; immunoassays of protozoa G01N33/56905; protozoa in screening assays C12Q1/025)}
- A61K 2039/54: {characterised by the route of administration}
- A61K 2039/545: {characterised by the dose, timing or administration schedule}
- C07K 2317/54: F(ab')2
- C07K 2317/55: Fab or Fab'
- C07K 2317/567: Framework region [FR]
- C07K 2317/622: Single chain antibody (scFv)
- C07K 2317/76: Antagonist effect on antigen, e.g. neutralization or inhibition of binding
- C07K: PEPTIDES (peptides in foodstuffs A23; obtaining protein compositions for foodstuffs, working-up proteins for foodstuffs A23J; preparations for medicinal purposes A61K; peptides containing beta-lactam rings C07D; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, C07D; ergot alkaloids of the cyclic peptide type C07D519/02; macromolecular compounds having statistically distributed amino acid units in their molecules, i.e. when the preparation does not provide for a specific; but for a random sequence of the amino acid units, homopolyamides and block copolyamides derived from amino acids C08G69/00; macromolecular products derived from proteins C08H1/00; preparation of glue or gelatine C09H; single cell proteins, enzymes C12N; genetic engineering processes for obtaining peptides C12N15/00; compositions for measuring or testing processes involving enzymes C12Q; investigation or analysis of biological material G01N33/00)
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- C12N: MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA (microbiological testing media C12Q1/00)
- C12Q: MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS (immunoassay G01N33/53); COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
- G01N: INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES (measuring or testing apparatus or processes other than immunoassay, involving enzymes or microorganisms C12M, C12Q)
- A61K: PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES (devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms A61J3/00; chemical aspects of, or use of materials for deodorisation of air, for disinfection or sterilisation, or for bandages, dressings, absorbent pads or surgical articles A61L; soap compositions C11D)

## Abstract

The invention provides methods of dosing for the treatment of cancers. In particular, provided are methods for treating human patients having lung cancer, such as non-small cell lung cancer (NSCLC), by administering a combination of an anti-TIGIT antagonist antibody and an anti-PD-L1 antagonist antibody.

## Claims

### Claim 1

A method for treating a subject having a lung cancer, the method comprising administering to the subject one or more dosing cycles of an anti-TIGIT antagonist antibody at a fixed dose of between about 30 mg to about 1200 mg every three weeks and an anti-PD-L1 antagonist antibody at a fixed dose of between about 80 mg to about 1600 mg every three weeks.

### Claim 2 (depends on 1)

The method of claim 1, wherein the method comprises administering to the subject an anti-TIGIT antagonist antibody at a fixed dose of between about 30 mg to about 600 mg every three weeks.

### Claim 3 (depends on 2)

The method of claim 2, wherein the method comprises administering to the subject an anti-TIGIT antagonist antibody at a fixed dose of about 600 mg every three weeks.

### Claim 4 (depends on 1, 2, 3)

The method of any one of claims 1-3, wherein the anti-TIGIT antagonist antibody comprises the following hypervariable regions (HVRs):
an HVR-H1 sequence comprising the amino acid sequence of SNSAAWN (SEQ ID NO: 1);
an HVR-H2 sequence comprising the amino acid sequence of KTYYRFKWYSDYAVSVKG (SEQ ID NO: 2);
an HVR-H3 sequence comprising the amino acid sequence of ESTTYDLLAGPFDY (SEQ ID NO: 3);
an HVR-L1 sequence comprising the amino acid sequence of KSSQTVLYSSNNKKYLA (SEQ ID NO: 4);
an HVR-L2 sequence comprising the amino acid sequence of WASTRES (SEQ ID NO: 5); and
an HVR-L3 sequence comprising the amino acid sequence of QQYYSTPFT (SEQ ID NO: 6).

### Claim 5 (depends on 4)

The method of claim 4, wherein the anti-TIGIT antagonist antibody further comprises the following light chain variable region framework regions (FRs):
an FR-L1 comprising the amino acid sequence of DIVMTQSPDSLAVSLGERATINC (SEQ ID NO: 7);
an FR-L2 comprising the amino acid sequence of WYQQKPGQPPNLLIY (SEQ ID NO: 8);
an FR-L3 comprising the amino acid sequence of GVPDRFSGSGSGTDFTLTISSLQAEDVAVYYC (SEQ ID NO: 9); and
an FR-L4 comprising the amino acid sequence of FGPGTKVEIK (SEQ ID NO: 10).

### Claim 6 (depends on 4)

The method of claim 4, wherein the anti-TIGIT antagonist antibody further comprises the following heavy chain variable region FRs:
an FR-H1 comprising the amino acid sequence of X1VQLQQSGPGLVKPSQTLSLTCAISGDSVS (SEQ ID NO: 11), wherein X1 is Q or E;
an FR-H2 comprising the amino acid sequence of WIRQSPSRGLEWLG (SEQ ID NO: 12);
an FR-H3 comprising the amino acid sequence of RITINPDTSKNQFSLQLNSVTPEDTAVFYCTR (SEQ ID NO: 13); and
an FR-H4 comprising the amino acid sequence of WGQGTLVTVSS (SEQ ID NO: 14).

### Claim 7 (depends on 6)

The method of claim 6, wherein X1 is Q.

### Claim 8 (depends on 6)

The method of claim 6, wherein X1 is E.

### Claim 9 (depends on 4, 5, 6, 7, 8)

The method of any one of claims 4-8, wherein the anti-TIGIT antagonist antibody comprises:
(a) a heavy chain variable (VH) domain comprising an amino acid sequence having at least 95% sequence identity to the amino acid sequence of SEQ ID NO: 17 or 18;
(b) a light chain variable (VL) domain comprising an amino acid sequence having at least 95% sequence identity to the amino acid sequence of SEQ ID NO: 19; or
(c) a VH domain as in (a) and a VL domain as in (b).

### Claim 10 (depends on 1, 2, 3, 4, 5, 6, 7, 8, 9)

The method of any one of claims 1-9, wherein the anti-TIGIT antagonist antibody comprises:
a VH domain comprising the amino acid sequence of SEQ ID NO: 17 or 18; and
a VL domain comprising the amino acid sequence of SEQ ID NO: 19.

### Claim 11 (depends on 1, 2, 3, 4, 5, 6, 7, 8, 9, 10)

The method of any one of claims 1-10, wherein the anti-TIGIT antagonist antibody is a monoclonal antibody.

### Claim 12 (depends on 11)

The method of claim 11, wherein the anti-TIGIT antagonist antibody is a human antibody.

### Claim 13 (depends on 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12)

The method of any one of claims 1-12, wherein the anti-TIGIT antagonist antibody is a full-length antibody.

### Claim 14 (depends on 1, 2, 3, 4, 5, 6, 8, 9, 10, 11, 12, 13)

The method of any one of claims 1-6 and 8-13, wherein the anti-TIGIT antagonist antibody is tiragolumab.

### Claim 15 (depends on 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12)

The method of any one of claims 1-12, wherein the anti-TIGIT antagonist antibody is an antibody fragment that binds TIGIT selected from the group consisting of Fab, Fab′, Fab′-SH, Fv, single chain variable fragment (scFv), and (Fab′)2 fragments.

### Claim 16 (depends on 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15)

The method of any one of claims 1-15, wherein the anti-TIGIT antagonist antibody is an IgG class antibody.

### Claim 17 (depends on 16)

The method of claim 16, wherein the IgG class antibody is an IgG1 subclass antibody.

### Claim 18 (depends on 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17)

The method of any one of claims 1-17, the method comprises administering to the subject an anti-PD-L1 antibody at a fixed dose of about 1200 mg every three weeks.

### Claim 19 (depends on 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18)

The method of any one of claims 1-18, wherein the anti-PD-L1 antagonist antibody is atezolizumab (MPDL3280A), YW243.55.S70, MSB0010718C, MDX-1105, or MEDI4736.

### Claim 20 (depends on 19)

The method of claim 19, wherein the anti-PD-L1 antagonist antibody is atezolizumab.

### Claim 21 (depends on 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18)

The method of any one of claims 1-18, wherein the anti-PD-L1 antagonist antibody comprises the following HVRs:
an HVR-H1 sequence comprising the amino acid sequence of GFTFSDSWIH (SEQ ID NO: 20);
an HVR-H2 sequence comprising the amino acid sequence of AWISPYGGSTYYADSVKG (SEQ ID NO: 21);
an HVR-H3 sequence comprising the amino acid sequence of RHWPGGFDY (SEQ ID NO: 22);
an HVR-L1 sequence comprising the amino acid sequence of RASQDVSTAVA (SEQ ID NO: 23);
an HVR-L2 sequence comprising the amino acid sequence of SASFLYS (SEQ ID NO: 24); and
an HVR-L3 sequence comprising the amino acid sequence of QQYLYHPAT (SEQ ID NO: 25).

### Claim 22 (depends on 21)

The method of claim 21, wherein the anti-PD-L1 antagonist antibody comprises:
(a) a heavy chain variable (VH) domain comprising an amino acid sequence having at least 95% sequence identity to the amino acid sequence of SEQ ID NO: 26;
(b) a light chain variable (VL) domain comprising an amino acid sequence having at least 95% sequence identity to the amino acid sequence of SEQ ID NO: 27; or
(c) a VH domain as in (a) and a VL domain as in (b).

### Claim 23 (depends on 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22)

The method of any one of claims 1-22, wherein the anti-PD-L1 antagonist antibody comprises:
a VH domain comprising the amino acid sequence of SEQ ID NO: 26; and
a VL domain comprising the amino acid sequence of SEQ ID NO: 27.

### Claim 24 (depends on 21, 22, 23)

The method of any one of claims 21-23, wherein the anti-PD-L1 antagonist antibody is a monoclonal antibody.

### Claim 25 (depends on 24)

The method of claim 24, wherein the anti-PD-L1 antagonist antibody is a humanized antibody.

### Claim 26 (depends on 24, 25)

The method of claim 24 or 25, wherein the anti-PD-L1 antagonist antibody is a full-length antibody.

### Claim 27 (depends on 21, 22, 23, 24, 25)

The method of any one of claims 21-25, wherein the anti-PD-L1 antagonist antibody is an antibody fragment that binds PD-L1 selected from the group consisting of Fab, Fab′, Fab′-SH, Fv, single chain variable fragment (scFv), and (Fab′)2 fragments.

### Claim 28 (depends on 21, 22, 23, 24, 25, 26, 27)

The method of any one of claims 21-27, wherein the anti-PD-L1 antagonist antibody is an IgG class antibody.

### Claim 29 (depends on 28)

The method of claim 28, wherein the IgG class antibody is an IgG1 subclass antibody.

### Claim 30 (depends on 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29)

The method of any one of claims 1-29, wherein the method comprises administering to the subject the anti-TIGIT antagonist antibody at a fixed dose of about 600 mg every three weeks and the anti-PD-L1 antagonist antibody at a fixed dose of about 1200 mg every three weeks.

### Claim 31 (depends on 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30)

The method of any one of claims 1-30, wherein the length of each of the one or more dosing cycles is 21 days.

### Claim 32 (depends on 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31)

The method of any one of claims 1-31, wherein the method comprises administering to the subject the anti-TIGIT antagonist antibody and the anti-PD-L1 antagonist antibody on about Day 1 of each of the one or more dosing cycles.

### Claim 33 (depends on 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32)

The method of any one of claims 1-32, wherein the method comprises administering to the subject the anti-TIGIT antagonist antibody before the anti-PD-L1 antagonist antibody.

### Claim 34 (depends on 33)

The method of claim 33, wherein the method comprises a first observation period following administration of the anti-TIGIT antagonist antibody and second observation period following administration of the anti-PD-L1 antagonist antibody.

### Claim 35 (depends on 34)

The method of claim 34, wherein the first observation period and the second observation period are each between about 30 minutes to about 60 minutes in length.

### Claim 36 (depends on 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32)

The method of any one of claims 1-32, wherein the method comprises administering to the subject the anti-PD-L1 antagonist antibody before the anti-TIGIT antagonist antibody.

### Claim 37 (depends on 36)

The method of claim 36, wherein the method comprises a first observation period following administration of the anti-PD-L1 antagonist antibody and second observation period following administration of the anti-TIGIT antagonist antibody.

### Claim 38 (depends on 37)

The method of claim 37, wherein the first observation period and the second observation period are each between about 30 minutes to about 60 minutes in length.

### Claim 39 (depends on 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32)

The method of any one of claims 1-32, wherein the method comprises administering to the subject the anti-TIGIT antagonist antibody and the anti-PD-L1 antagonist antibody simultaneously.

### Claim 40 (depends on 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39)

The method of any one of claims 1-39, wherein the method comprises administering to the subject the anti-TIGIT antagonist antibody and anti-PD-L1 antagonist antibody intravenously.

### Claim 41 (depends on 40)

The method of claim 40, wherein the method comprises administering to the subject the anti-TIGIT antagonist antibody by intravenous infusion over 60±10 minutes.

### Claim 42 (depends on 40, 41)

The method of claim 40 or 41, wherein the method comprises administering to the subject the anti-PD-L1 antagonist antibody by intravenous infusion over 60±15 minutes.

### Claim 43 (depends on 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42)

The method of any one of claims 1-42, wherein a tumor sample obtained from the subject has been determined to have a detectable expression level of PD-L1.

### Claim 44 (depends on 43)

The method of claim 43, wherein the detectable expression level of PD-L1 is a detectable protein expression level of PD-L1.

### Claim 45 (depends on 44)

The method of claim 44, wherein the detectable protein expression level of PD-L1 has been determined by an immunohistochemical (IHC) assay.

### Claim 46 (depends on 45)

The method of claim 45, wherein the IHC assay uses anti-PD-L1 antibody 22C3, SP142, SP263, or 28-8.

### Claim 47 (depends on 46)

The method of claim 46, wherein the IHC assay uses anti-PD-L1 antibody 22C3.

### Claim 48 (depends on 47)

The method of claim 47, wherein the tumor sample has been determined to have a tumor proportion score (TPS) of greater than, or equal to, 1%.

### Claim 49 (depends on 48)

The method of claim 48, wherein the TPS is greater than, or equal to, 1% and less than 50%.

### Claim 50 (depends on 48)

The method of claim 48, wherein the TPS is greater than, or equal to, 50%.

### Claim 51 (depends on 46)

The method of claim 46, wherein the IHC assay uses anti-PD-L1 antibody SP142.

### Claim 52 (depends on 51)

The method of claim 51, wherein the tumor sample has been determined to have a detectable expression level of PD-L1 in greater than, or equal to, 1% of the tumor cells in the tumor sample.

### Claim 53 (depends on 52)

The method of claim 52, wherein the tumor sample has been determined to have a detectable expression level of PD-L1 in greater than, or equal to, 1% and less than 5% of the tumor cells in the tumor sample.

### Claim 54 (depends on 52)

The method of claim 52, wherein the tumor sample has been determined to have a detectable expression level of PD-L1 in greater than, or equal to, 5% and less than 50% of the tumor cells in the tumor sample.

### Claim 55 (depends on 52)

The method of claim 52, wherein the tumor sample has been determined to have a detectable expression level of PD-L1 in greater than, or equal to, 50% of the tumor cells in the tumor sample.

### Claim 56 (depends on 51, 52, 53, 54, 55)

The method of any one of claims 51-55, wherein the tumor sample has been determined to have a detectable expression level of PD-L1 in tumor-infiltrating immune cells that comprise greater than, or equal to, 1% of the tumor sample.

### Claim 57 (depends on 56)

The method of claim 56, wherein the tumor sample has been determined to have a detectable expression level of PD-L1 in tumor-infiltrating immune cells that comprise greater than, or equal to, 1% and less than 5% of the tumor sample.

### Claim 58 (depends on 56)

The method of claim 56, wherein the tumor sample has been determined to have a detectable expression level of PD-L1 in tumor-infiltrating immune cells that comprise greater than, or equal to, 5% and less than 10% of the tumor sample.

### Claim 59 (depends on 56)

The method of claim 56, wherein the tumor sample has been determined to have a detectable expression level of PD-L1 in tumor-infiltrating immune cells that comprise greater than, or equal to, 10% of the tumor sample.

### Claim 60 (depends on 43)

The method of claim 43, wherein the detectable expression level of PD-L1 is a detectable nucleic acid expression level of PD-L1.

### Claim 61 (depends on 60)

The method of claim 60, wherein the detectable nucleic acid expression level of PD-L1 has been determined by RNA-seq, RT-qPCR, qPCR, multiplex qPCR or RT-qPCR, microarray analysis, SAGE, MassARRAY technique, ISH, or a combination thereof.

### Claim 62 (depends on 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61)

The method of any one of claims 1-61, wherein the lung cancer is a non-small cell lung cancer (NSCLC).

### Claim 63 (depends on 62)

The method of claim 62, wherein the NSCLC is a squamous NSCLC.

### Claim 64 (depends on 62)

The method of claim 62, wherein the NSCLC is a non-squamous NSCLC.

### Claim 65 (depends on 62, 63, 64)

The method of any one of claims 62-64, wherein the NSCLC is a locally advanced unresectable NSCLC.

### Claim 66 (depends on 65)

The method of claim 65, wherein the NSCLC is a Stage IIIB NSCLC.

### Claim 67 (depends on 62, 63, 64)

The method of any one of claims 62-64, wherein the NSCLC is a recurrent or metastatic NSCLC.

### Claim 68 (depends on 67)

The method of claim 67, wherein the NSCLC is a Stage IV NSCLC.

### Claim 69 (depends on 67, 68)

The method of claim 67 or 68, wherein the subject has not been previously treated for Stage IV NSCLC.

### Claim 70 (depends on 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69)

The method of any one of claims 1-69, wherein the subject does not have a sensitizing epidermal growth factor receptor (EGFR) gene mutation or anaplastic lymphoma kinase (ALK) gene rearrangement.

### Claim 71 (depends on 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70)

The method of any one of claims 1-70, wherein the subject does not have a pulmonary lymphoepithelioma-like carcinoma subtype of NSCLC.

### Claim 72 (depends on 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71)

The method of any one of claims 1-71, wherein the subject does not have an active Epstein-Barr virus (EBV) infection or a known or suspected chronic active EBV infection.

### Claim 73 (depends on 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72)

The method of any one of claims 1-72, wherein the subject is negative for EBV IgM or negative by EBV PCR.

### Claim 74 (depends on 73)

The method of claim 73, wherein the subject is negative for EBV IgM and negative by EBV PCR.

### Claim 75 (depends on 73, 74)

The method of claim 73 or 74, wherein the subject is positive for EBV IgG or positive for Epstein-Barr nuclear antigen (EBNA).

### Claim 76 (depends on 75)

The method of claim 75, wherein the subject is positive for EBV IgG and positive for EBNA.

### Claim 77 (depends on 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74)

The method of any one of claims 1-74, wherein the subject is negative for EBV IgG or negative for EBNA.

### Claim 78 (depends on 77)

The method of claim 77, wherein the subject is negative for EBV IgG and negative for EBNA.

### Claim 79 (depends on 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78)

The method of any one of claims 1-78, wherein the treating results in a clinical response.

### Claim 80 (depends on 79)

The method of claim 79, wherein the clinical response is an increase in the objective response rate (ORR) of the subject as compared to a reference ORR.

### Claim 81 (depends on 80)

The method of claim 80, wherein the reference ORR is the median ORR of a population of subjects who have received a treatment comprising an anti-PD-L1 antagonist antibody without an anti-TIGIT antagonist antibody.

### Claim 82 (depends on 79, 80, 81)

The method of any one of claims 79-81, wherein the clinical response is an increase in the progression-free survival (PFS) of the subject as compared to a reference PFS time.

### Claim 83 (depends on 79, 80, 81, 82)

The method of any one of claims 79-82, wherein the reference PFS time is the median PFS time of a population of subjects who have received a treatment comprising an anti-PD-L1 antagonist antibody without an anti-TIGIT antagonist antibody.

### Claim 84

A method for treating a subject having a NSCLC, the method comprising administering to the subject one or more dosing cycles of an anti-TIGIT antagonist antibody at a fixed dose of 600 mg every three weeks and atezolizumab at a fixed dose of 1200 mg every three weeks, wherein the anti-TIGIT antagonist antibody comprises:
a VH domain comprising the amino acid sequence of SEQ ID NO: 17 or 18; and
a VL domain comprising the amino acid sequence of SEQ ID NO: 19.

### Claim 85

A method of treating a subject having a NSCLC, the method comprising:
(a) obtaining a tumor sample from the subject;
(b) detecting the protein expression level of PD-L1 in the tumor sample by an IHC assay using anti-PD-L1 antibody 22C3 and determining a TPS therefrom;
(c) identifying the subject as one who is likely to benefit from a therapy comprising one or more dosing cycles of an anti-TIGIT antagonist antibody administered at a fixed dose of 600 mg every three weeks and atezolizumab administered at a fixed dose of 1200 mg every three weeks based on the TPS having been determined to be greater than, or equal to, 1% and less than 50%, wherein the anti-TIGIT antagonist antibody comprises:
a VH domain comprising the amino acid sequence of SEQ ID NO: 17 or 18; and
a VL domain comprising the amino acid sequence of SEQ ID NO: 19; and
(d) administering to the identified subject the therapy.

### Claim 86

A method of treating a subject having a NSCLC, the method comprising:
(a) obtaining a tumor sample from the subject;
(b) detecting the protein expression level of PD-L1 in the tumor sample by an IHC assay using anti-PD-L1 antibody 22C3 and determining a TPS therefrom;
(c) identifying the subject as one who is likely to benefit from a therapy comprising one or more dosing cycles of an anti-TIGIT antagonist antibody administered at a fixed dose of 600 mg every three weeks and atezolizumab administered at a fixed dose of 1200 mg every three weeks based on the TPS having been determined to be greater than, or equal to, 50%, wherein the anti-TIGIT antagonist antibody comprises:
a VH domain comprising the amino acid sequence of SEQ ID NO: 17 or 18; and
a VL domain comprising the amino acid sequence of SEQ ID NO: 19; and
(d) administering to the identified subject the therapy.

### Claim 87

A method of selecting a therapy for a subject having a NSCLC, the method comprising:
(a) determining a TPS from a tumor sample from the subject by an IHC assay using anti-PD-L1 antibody 22C3; and
(b) selecting for the subject a therapy comprising one or more dosing cycles of an anti-TIGIT antagonist antibody administered at a fixed dose of 600 mg every three weeks and atezolizumab administered at a fixed dose of 1200 mg every three weeks based on the TPS having been determined to be greater than, or equal to, 1% and less than 50%, wherein the anti-TIGIT antagonist antibody comprises:
a VH domain comprising the amino acid sequence of SEQ ID NO: 17 or 18; and
a VL domain comprising the amino acid sequence of SEQ ID NO: 19.

### Claim 88

A method of selecting a therapy for a subject having a NSCLC, the method comprising:
(a) determining a TPS from a tumor sample from the subject by an IHC assay using anti-PD-L1 antibody 22C3; and
(b) selecting for the subject a therapy comprising one or more dosing cycles of an anti-TIGIT antagonist antibody administered at a fixed dose of 600 mg every three weeks and atezolizumab administered at a fixed dose of 1200 mg every three weeks based on the TPS having been determined to be greater than, or equal to, 50%, wherein the anti-TIGIT antagonist antibody comprises:
a VH domain comprising the amino acid sequence of SEQ ID NO: 17 or 18; and
a VL domain comprising the amino acid sequence of SEQ ID NO: 19.

### Claim 89

A method of selecting a therapy for a subject having a NSCLC, the method comprising:
(a) detecting the mutational status of the epidermal growth factor receptor (EGFR) gene and anaplastic lymphoma kinase (ALK) gene from a sample from the subject and detecting the absence of a sensitizing EGFR gene mutation or ALK gene rearrangement; and
(b) selecting for the subject a therapy comprising one or more dosing cycles of an anti-TIGIT antagonist antibody administered at a fixed dose of 600 mg every three weeks and atezolizumab administered at a fixed dose of 1200 mg every three weeks, based on the subject not having a sensitizing EGFR gene mutation or ALK gene rearrangement, wherein the anti-TIGIT antagonist antibody comprises:
a VH domain comprising the amino acid sequence of SEQ ID NO: 17 or 18; and
a VL domain comprising the amino acid sequence of SEQ ID NO: 19.

### Claim 90

A method of selecting a therapy for a subject having a NSCLC, the method comprising:
(a) biopsying a tumor sample from the subject and detecting a subtype of the NSCLC other than a pulmonary lymphoepithelioma-like carcinoma; and
(b) selecting for the subject a therapy comprising one or more dosing cycles of an anti-TIGIT antagonist antibody administered at a fixed dose of 600 mg every three weeks and atezolizumab administered at a fixed dose of 1200 mg every three weeks, based on the subject not having a pulmonary lymphoepithelioma-like carcinoma subtype of NSCLC, wherein the anti-TIGIT antagonist antibody comprises:
a VH domain comprising the amino acid sequence of SEQ ID NO: 17 or 18; and
a VL domain comprising the amino acid sequence of SEQ ID NO: 19.

### Claim 91

A method of selecting a therapy for a subject having a NSCLC, the method comprising:
(a) detecting the presence of one or more of Epstein-Barr virus (EBV) IgM, EBV IgG, Epstein-Barr nuclear antigen (EBNA), and Epstein-Barr viral particles in a sample from the subject, and
(b) selecting for the subject a therapy comprising one or more dosing cycles of an anti-TIGIT antagonist antibody administered at a fixed dose of 600 mg every three weeks and atezolizumab administered at a fixed dose of 1200 mg every three weeks, on based on the subject being:
(i) negative for EBV IgG and/or EBNA; or
(ii) positive for EBV IgG and/or EBNA, and negative for both EBV IgM and Epstein-Barr viral particles,
wherein the anti-TIGIT antagonist antibody comprises:
a VH domain comprising the amino acid sequence of SEQ ID NO: 17 or 18; and
a VL domain comprising the amino acid sequence of SEQ ID NO: 19.

### Claim 92

A method for treating a subject having a NSCLC, the method comprising administering to the subject one or more dosing cycles of tiragolumab at a fixed dose of 600 mg every three weeks and atezolizumab at a fixed dose of 1200 mg every three weeks.

### Claim 93

A method of treating a subject having a NSCLC, the method comprising:
(a) obtaining a tumor sample from the subject;
(b) detecting the protein expression level of PD-L1 in the tumor sample by an IHC assay using anti-PD-L1 antibody 22C3 and determining a TPS therefrom;
(c) identifying the subject as one who is likely to benefit from a therapy comprising one or more dosing cycles of tiragolumab administered at a fixed dose of 600 mg every three weeks and atezolizumab administered at a fixed dose of 1200 mg every three weeks based on the TPS having been determined to be greater than, or equal to, 1% and less than 50%; and
(d) administering to the identified subject the therapy.

### Claim 94

A method of treating a subject having a NSCLC, the method comprising:
(a) obtaining a tumor sample from the subject;
(b) detecting the protein expression level of PD-L1 in the tumor sample by an IHC assay using anti-PD-L1 antibody 22C3 and determining a TPS therefrom;
(c) identifying the subject as one who is likely to benefit from a therapy comprising one or more dosing cycles of tiragolumab administered at a fixed dose of 600 mg every three weeks and atezolizumab administered at a fixed dose of 1200 mg every three weeks based on the TPS having been determined to be greater than, or equal to, 50%; and
(d) administering to the identified subject the therapy.

### Claim 95

A method of selecting a therapy for a subject having a NSCLC, the method comprising:
(a) determining a TPS from a tumor sample from the subject by an IHC assay using anti-PD-L1 antibody 22C3; and
(b) selecting for the subject a therapy comprising one or more dosing cycles of tiragolumab administered at a fixed dose of 600 mg every three weeks and atezolizumab administered at a fixed dose of 1200 mg every three weeks based on the TPS having been determined to be greater than, or equal to, 1% and less than 50%.

### Claim 96

A method of selecting a therapy for a subject having a NSCLC, the method comprising:
(a) determining a TPS from a tumor sample from the subject by an IHC assay using anti-PD-L1 antibody 22C3; and
(b) selecting for the subject a therapy comprising one or more dosing cycles of tiragolumab administered at a fixed dose of 600 mg every three weeks and atezolizumab administered at a fixed dose of 1200 mg every three weeks based on the TPS having been determined to be greater than, or equal to, 50%.

### Claim 97

A method of selecting a therapy for a subject having a NSCLC, the method comprising:
(a) detecting the mutational status of the epidermal growth factor receptor (EGFR) gene and anaplastic lymphoma kinase (ALK) gene from a sample from the subject and detecting the absence of a sensitizing EGFR gene mutation or ALK gene rearrangement; and
(b) selecting for the subject a therapy comprising one or more dosing cycles of tiragolumab administered at a fixed dose of 600 mg every three weeks and atezolizumab administered at a fixed dose of 1200 mg every three weeks, based on the subject not having a sensitizing EGFR gene mutation or ALK gene rearrangement.

### Claim 98

A method of selecting a therapy for a subject having a NSCLC, the method comprising:
(a) biopsying a tumor sample from the subject and detecting a subtype of the NSCLC other than a pulmonary lymphoepithelioma-like carcinoma; and
(b) selecting for the subject a therapy comprising one or more dosing cycles of tiragolumab administered at a fixed dose of 600 mg every three weeks and atezolizumab administered at a fixed dose of 1200 mg every three weeks, based on the subject not having a pulmonary lymphoepithelioma-like carcinoma subtype of NSCLC.

### Claim 99

A method of selecting a therapy for a subject having a NSCLC, the method comprising:
(a) detecting the presence of one or more of Epstein-Barr virus (EBV) IgM, EBV IgG, Epstein-Barr nuclear antigen (EBNA), and Epstein-Barr viral particles in a sample from the subject, and
(b) selecting for the subject a therapy comprising one or more dosing cycles of tiragolumab administered at a fixed dose of 600 mg every three weeks and atezolizumab administered at a fixed dose of 1200 mg every three weeks, on based on the subject being:
(i) negative for EBV IgG and/or EBNA; or
(ii) positive for EBV IgG and/or EBNA, and negative for both EBV IgM and Epstein-Barr viral particles.

### Claim 100

An anti-TIGIT antagonist antibody and an anti-PD-L1 antagonist antibody for use in a method of treating a subject having a lung cancer, wherein the method comprises administering to the subject one or more dosing cycles of the anti-TIGIT antagonist antibody at a fixed dose of between about 30 mg to about 1200 mg every three weeks and the anti-PD-L1 antagonist antibody at a fixed dose of between about 80 mg to about 1600 mg every three weeks.

### Claim 101 (depends on 100)

The anti-TIGIT antagonist antibody and anti-PD-L1 antagonist antibody for use of claim 100, wherein the anti-TIGIT antagonist antibody is to be administered to the subject at a fixed dose of between about 30 mg to about 600 mg every three weeks.

### Claim 102 (depends on 101)

The anti-TIGIT antagonist antibody and anti-PD-L1 antagonist antibody for use of claim 101, wherein the anti-TIGIT antagonist antibody is to be administered to the subject at a fixed dose of about 600 mg every three weeks.

### Claim 103 (depends on 100, 101, 102)

The anti-TIGIT antagonist antibody and anti-PD-L1 antagonist antibody for use of any one of claims 100-102, wherein the anti-TIGIT antagonist antibody comprises the following HVRs:
an HVR-H1 sequence comprising the amino acid sequence of SNSAAWN (SEQ ID NO: 1);
an HVR-H2 sequence comprising the amino acid sequence of KTYYRFKWYSDYAVSVKG (SEQ ID NO: 2);
an HVR-H3 sequence comprising the amino acid sequence of ESTTYDLLAGPFDY (SEQ ID NO: 3);
an HVR-L1 sequence comprising the amino acid sequence of KSSQTVLYSSNNKKYLA (SEQ ID NO: 4);
an HVR-L2 sequence comprising the amino acid sequence of WASTRES (SEQ ID NO: 5); and
an HVR-L3 sequence comprising the amino acid sequence of QQYYSTPFT (SEQ ID NO: 6).

### Claim 104 (depends on 103)

The anti-TIGIT antagonist antibody and anti-PD-L1 antagonist antibody for use of claim 103, wherein the anti-TIGIT antagonist antibody further comprises the following light chain variable region FRs:
an FR-L1 comprising the amino acid sequence of DIVMTQSPDSLAVSLGERATINC (SEQ ID NO: 7);
an FR-L2 comprising the amino acid sequence of WYQQKPGQPPNLLIY (SEQ ID NO: 8);
an FR-L3 comprising the amino acid sequence of GVPDRFSGSGSGTDFTLTISSLQAEDVAVYYC (SEQ ID NO: 9); and
an FR-L4 comprising the amino acid sequence of FGPGTKVEIK (SEQ ID NO: 10).

### Claim 105 (depends on 103)

The anti-TIGIT antagonist antibody and anti-PD-L1 antagonist antibody for use of claim 103, wherein the anti-TIGIT antagonist antibody further comprises the following heavy chain variable region FRs:
an FR-H1 comprising the amino acid sequence of X1VQLQQSGPGLVKPSQTLSLTCAISGDSVS (SEQ ID NO: 11), wherein X1 is Q or E;
an FR-H2 comprising the amino acid sequence of WIRQSPSRGLEWLG (SEQ ID NO: 12);
an FR-H3 comprising the amino acid sequence of RITINPDTSKNQFSLQLNSVTPEDTAVFYCTR (SEQ ID NO: 13); and
an FR-H4 comprising the amino acid sequence of WGQGTLVTVSS (SEQ ID NO: 14).

### Claim 106 (depends on 105)

The anti-TIGIT antagonist antibody and anti-PD-L1 antagonist antibody for use of claim 105, wherein X1 is Q.

### Claim 107 (depends on 105)

The anti-TIGIT antagonist antibody and anti-PD-L1 antagonist antibody of claim 105, wherein X1 is E.

### Claim 108 (depends on 103, 104, 105, 106, 107)

The anti-TIGIT antagonist antibody and anti-PD-L1 antagonist antibody for use of any one of claims 103-107, wherein the anti-TIGIT antagonist antibody comprises:
(a) a heavy chain variable (VH) domain comprising an amino acid sequence having at least 95% sequence identity to the amino acid sequence of SEQ ID NO: 17 or 18;
(b) a light chain variable (VL) domain comprising an amino acid sequence having at least 95% sequence identity to the amino acid sequence of SEQ ID NO: 19; or
(c) a VH domain as in (a) and a VL domain as in (b).

### Claim 109 (depends on 100, 101, 102, 103, 104, 105, 106, 107, 108)

The anti-TIGIT antagonist antibody and anti-PD-L1 antagonist antibody for use of any one of claims 100-108, wherein the anti-TIGIT antagonist antibody comprises:
a VH domain comprising the amino acid sequence of SEQ ID NO: 17 or 18; and
a VL domain comprising the amino acid sequence of SEQ ID NO: 19.

### Claim 110 (depends on 100, 101, 102, 103, 104, 105, 106, 107, 108, 109)

The anti-TIGIT antagonist antibody and anti-PD-L1 antagonist antibody for use of any one of claims 100-109, wherein the anti-TIGIT antagonist antibody is a monoclonal antibody.

### Claim 111 (depends on 110)

The anti-TIGIT antagonist antibody and anti-PD-L1 antagonist antibody for use of claim 110, wherein the anti-TIGIT antagonist antibody is a human antibody.

### Claim 112 (depends on 100, 101, 102, 103, 104, 105, 106, 107, 108, 109, 110, 111)

The anti-TIGIT antagonist antibody and anti-PD-L1 antagonist antibody for use of any one of claims 100-111, wherein the anti-TIGIT antagonist antibody is a full-length antibody.

### Claim 113 (depends on 100, 101, 102, 103, 104, 105, 107, 108, 109, 110, 111, 112)

The anti-TIGIT antagonist antibody and anti-PD-L1 antagonist antibody for use of any one of claims 100-105 and 107-112, wherein the anti-TIGIT antagonist antibody is tiragolumab.

### Claim 114 (depends on 100, 101, 102, 103, 104, 105, 106, 107, 108, 109, 110, 111)

The anti-TIGIT antagonist antibody and anti-PD-L1 antagonist antibody for use of any one of claims 100-111, wherein the anti-TIGIT antagonist antibody is an antibody fragment that binds TIGIT selected from the group consisting of Fab, Fab′, Fab′-SH, Fv, single chain variable fragment (scFv), and (Fab′)2 fragments.

### Claim 115 (depends on 100, 101, 102, 103, 104, 105, 106, 107, 108, 109, 110, 111, 112, 113, 114)

The anti-TIGIT antagonist antibody and anti-PD-L1 antagonist antibody for use of any one of claims 100-114, wherein the anti-TIGIT antagonist antibody is an IgG class antibody.

### Claim 116 (depends on 115)

The anti-TIGIT antagonist antibody and anti-PD-L1 antagonist antibody for use of claim 115, wherein the IgG class antibody is an IgG1 subclass antibody.

### Claim 117 (depends on 100, 101, 102, 103, 104, 105, 106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116)

The anti-TIGIT antagonist antibody and anti-PD-L1 antagonist antibody for use of any one of claims 100-116, wherein the anti-PD-L1 antagonist antibody is to be administered to the subject at a fixed dose of about 1200 mg every three weeks.

### Claim 118 (depends on 100, 101, 102, 103, 104, 105, 106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117)

The anti-TIGIT antagonist antibody and anti-PD-L1 antagonist antibody for use of any one of claims 100-117, wherein the anti-PD-L1 antagonist antibody is atezolizumab (MPDL3280A), YW243.55.S70, MSB0010718C, MDX-1105, or MEDI4736.

### Claim 119 (depends on 118)

The anti-TIGIT antagonist antibody and anti-PD-L1 antagonist antibody for use of claim 118, wherein the anti-PD-L1 antagonist antibody is atezolizumab.

### Claim 120 (depends on 100, 101, 102, 103, 104, 105, 106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117)

The anti-TIGIT antagonist antibody and anti-PD-L1 antagonist antibody for use of any one of claims 100-117, wherein the anti-PD-L1 antagonist antibody comprises the following HVRs:
an HVR-H1 sequence comprising the amino acid sequence of GFTFSDSWIH (SEQ ID NO: 20);
an HVR-H2 sequence comprising the amino acid sequence of AWISPYGGSTYYADSVKG (SEQ ID NO: 21);
an HVR-H3 sequence comprising the amino acid sequence of RHWPGGFDY (SEQ ID NO: 22);
an HVR-L1 sequence comprising the amino acid sequence of RASQDVSTAVA (SEQ ID NO: 23);
an HVR-L2 sequence comprising the amino acid sequence of SASFLYS (SEQ ID NO: 24); and
an HVR-L3 sequence comprising the amino acid sequence of QQYLYHPAT (SEQ ID NO: 25).

### Claim 121 (depends on 120)

The anti-TIGIT antagonist antibody and anti-PD-L1 antagonist antibody for use of claim 120, wherein the anti-PD-L1 antagonist antibody comprises:
(a) a heavy chain variable (VH) domain comprising an amino acid sequence having at least 95% sequence identity to the amino acid sequence of SEQ ID NO: 26;
(b) a light chain variable (VL) domain comprising an amino acid sequence having at least 95% sequence identity to the amino acid sequence of SEQ ID NO: 27; or
(c) a VH domain as in (a) and a VL domain as in (b).

### Claim 122 (depends on 100, 101, 102, 103, 104, 105, 106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 118, 119, 120, 121)

The anti-TIGIT antagonist antibody and anti-PD-L1 antagonist antibody for use of any one of claims 100-121, wherein the anti-PD-L1 antagonist antibody comprises:
a VH domain comprising the amino acid sequence of SEQ ID NO: 26; and
a VL domain comprising the amino acid sequence of SEQ ID NO: 27.

### Claim 123 (depends on 120, 121, 122)

The anti-TIGIT antagonist antibody and anti-PD-L1 antagonist antibody for use of any one of claims 120-122, wherein the anti-PD-L1 antagonist antibody is a monoclonal antibody.

### Claim 124 (depends on 123)

The anti-TIGIT antagonist antibody and anti-PD-L1 antagonist antibody for use of claim 123, wherein the anti-PD-L1 antagonist antibody is a humanized antibody.

### Claim 125 (depends on 123, 124)

The anti-TIGIT antagonist antibody and anti-PD-L1 antagonist antibody for use of claim 123 or 124, wherein the anti-PD-L1 antagonist antibody is a full-length antibody.

### Claim 126 (depends on 120, 121, 122, 123, 124)

The anti-TIGIT antagonist antibody and anti-PD-L1 antagonist antibody for use of any one of claims 120-124, wherein the anti-PD-L1 antagonist antibody is an antibody fragment that binds PD-L1 selected from the group consisting of Fab, Fab′, Fab′-SH, Fv, single chain variable fragment (scFv), and (Fab′)2 fragments.

### Claim 127 (depends on 120, 121, 122, 123, 124, 125, 126)

The anti-TIGIT antagonist antibody and anti-PD-L1 antagonist antibody for use of any one of claims 120-126, wherein the anti-PD-L1 antagonist antibody is an IgG class antibody.

### Claim 128 (depends on 127)

The anti-TIGIT antagonist antibody and anti-PD-L1 antagonist antibody for use of claim 127, wherein the IgG class antibody is an IgG1 subclass antibody.

### Claim 129 (depends on 100, 101, 102, 103, 104, 105, 106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 118, 119, 120, 121, 122, 123, 124, 125, 126, 127, 128)

The anti-TIGIT antagonist antibody and anti-PD-L1 antagonist antibody for use of any one of claims 100-128, wherein the anti-TIGIT antagonist antibody is to be administered to the subject at a fixed dose of about 600 mg every three weeks and the anti-PD-L1 antagonist antibody is to be administered to the subject at a fixed dose of about 1200 mg every three weeks.

### Claim 130 (depends on 100, 101, 102, 103, 104, 105, 106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 118, 119, 120, 121, 122, 123, 124, 125, 126, 127, 128, 129)

The anti-TIGIT antagonist antibody and anti-PD-L1 antagonist antibody for use of any one of claims 100-129, wherein the length of each of the one or more dosing cycles is 21 days.

### Claim 131 (depends on 100, 101, 102, 103, 104, 105, 106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 118, 119, 120, 121, 122, 123, 124, 125, 126, 127, 128, 129, 130)

The anti-TIGIT antagonist antibody and anti-PD-L1 antibody for use of any one of claims 100-130, wherein the anti-TIGIT antagonist antibody and anti-PD-L1 antagonist antibody are to be administered to the subject on about Day 1 of each of the one or more dosing cycles.

### Claim 132 (depends on 100, 101, 102, 103, 104, 105, 106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 118, 119, 120, 121, 122, 123, 124, 125, 126, 127, 128, 129, 130, 131)

The anti-TIGIT antagonist antibody and anti-PD-L1 antagonist antibody for use of any one of claims 100-131, wherein the anti-TIGIT antagonist antibody is to be administered to the subject before the anti-PD-L1 antagonist antibody.

### Claim 133 (depends on 132)

The anti-TIGIT antagonist antibody and anti-PD-L1 antagonist antibody for use of claim 132, wherein a first observation period is to follow administration of the anti-TIGIT antagonist antibody and second observation period is to follow administration of the anti-PD-L1 antagonist antibody.

### Claim 134 (depends on 133)

The anti-TIGIT antagonist antibody and anti-PD-L1 antagonist antibody for use of claim 133, wherein the first observation period and the second observation period are each between about 30 minutes to about 60 minutes in length.

### Claim 135 (depends on 100, 101, 102, 103, 104, 105, 106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 118, 119, 120, 121, 122, 123, 124, 125, 126, 127, 128, 129, 130, 131)

The anti-TIGIT antagonist antibody and anti-PD-L1 antagonist antibody for use of any one of claims 100-131, wherein the anti-PD-L1 antagonist antibody is to be administered to the subject before the anti-TIGIT antagonist antibody.

### Claim 136 (depends on 135)

The anti-TIGIT antagonist antibody and anti-PD-L1 antagonist antibody for use of claim 135, wherein a first observation period is to follow administration of the anti-PD-L1 antagonist antibody and second observation period is to follow administration of the anti-TIGIT antagonist antibody.

### Claim 137 (depends on 136)

The anti-TIGIT antagonist antibody and anti-PD-L1 antagonist antibody for use of claim 136, wherein the first observation period and the second observation period are each between about 30 minutes to about 60 minutes in length.

### Claim 138 (depends on 100, 101, 102, 103, 104, 105, 106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 118, 119, 120, 121, 122, 123, 124, 125, 126, 127, 128, 129, 130, 131)

The anti-TIGIT antagonist antibody and anti-PD-L1 antagonist antibody for use of any one of claims 100-131, wherein the anti-TIGIT antagonist antibody is to be administered to the subject simultaneously with the anti-PD-L1 antagonist antibody.

### Claim 139 (depends on 100, 101, 102, 103, 104, 105, 106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 118, 119, 120, 121, 122, 123, 124, 125, 126, 127, 128, 129, 130, 131, 132, 133, 134, 135, 136, 137, 138)

The anti-TIGIT antagonist antibody and anti-PD-L1 antagonist antibody for use of any one of claims 100-138, wherein the anti-TIGIT antagonist antibody and anti-PD-L1 antagonist antibody are to be administered to the subject intravenously.

### Claim 140 (depends on 139)

The anti-TIGIT antagonist antibody and anti-PD-L1 antagonist antibody for use of claim 139, wherein the anti-TIGIT antagonist antibody is to be administered to the subject by intravenous infusion over 60±10 minutes.

### Claim 141 (depends on 139, 140)

The anti-TIGIT antagonist antibody and anti-PD-L1 antagonist antibody for use of claim 139 or 140, wherein the anti-PD-L1 antagonist antibody is to be administered to the subject by intravenous infusion over 60±15 minutes.

### Claim 142 (depends on 100, 101, 102, 103, 104, 105, 106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 118, 119, 120, 121, 122, 123, 124, 125, 126, 127, 128, 129, 130, 131, 132, 133, 134, 135, 136, 137, 138, 139, 140, 141)

The anti-TIGIT antagonist antibody and anti-PD-L1 antagonist antibody for use of any one of claims 100-141, wherein a tumor sample obtained from the subject has been determined to have a detectable expression level of PD-L1.

### Claim 143 (depends on 142)

The anti-TIGIT antagonist antibody and anti-PD-L1 antibody for use of claim 142, wherein the detectable expression level of PD-L1 is a detectable protein expression level of PD-L1.

### Claim 144 (depends on 143)

The anti-TIGIT antagonist antibody and anti-PD-L1 antagonist antibody for use of claim 143, wherein the detectable protein expression level of PD-L1 has been determined by an immunohistochemical (IHC) assay.

### Claim 145 (depends on 144)

The anti-TIGIT antagonist antibody and anti-PD-L1 antagonist antibody for use of claim 144, wherein the IHC assay uses anti-PD-L1 antibody 22C3, SP142, SP263, or 28-8.

### Claim 146 (depends on 145)

The anti-TIGIT antagonist antibody and anti-PD-L1 antagonist antibody for use of claim 145, wherein the IHC assay uses anti-PD-L1 antibody 22C3.

### Claim 147 (depends on 146)

The anti-TIGIT antagonist antibody and anti-PD-L1 antagonist antibody for use of claim 146, wherein the tumor sample has been determined to have a tumor proportion score (TPS) of greater than, or equal to, 1%.

### Claim 148 (depends on 147)

The anti-TIGIT antagonist antibody and anti-PD-L1 antagonist antibody for use of claim 147, wherein the TPS is greater than, or equal to, 1% and less than 50%.

### Claim 149 (depends on 147)

The anti-TIGIT antagonist antibody and anti-PD-L1 antagonist antibody for use of claim 147, wherein the TPS is greater than, or equal to, 50%.

### Claim 150 (depends on 145)

The anti-TIGIT antagonist antibody and anti-PD-L1 antagonist antibody for use of claim 145, wherein the IHC assay uses anti-PD-L1 antibody SP142.

### Claim 151 (depends on 150)

The anti-TIGIT antagonist antibody and anti-PD-L1 antagonist antibody for use of claim 150, wherein the tumor sample has been determined to have a detectable expression level of PD-L1 in greater than, or equal to, 1% of the tumor cells in the tumor sample.

### Claim 152 (depends on 151)

The anti-TIGIT antagonist antibody and anti-PD-L1 antagonist antibody for use of claim 151, wherein the tumor sample has been determined to have a detectable expression level of PD-L1 in greater than, or equal to, 1% and less than 5% of the tumor cells in the tumor sample.

### Claim 153 (depends on 151)

The anti-TIGIT antagonist antibody and anti-PD-L1 antagonist antibody for use of claim 151, wherein the tumor sample has been determined to have a detectable expression level of PD-L1 in greater than, or equal to, 5% and less than 50% of the tumor cells in the tumor sample.

### Claim 154 (depends on 151)

The anti-TIGIT antagonist antibody and anti-PD-L1 antagonist antibody for use of claim 151, wherein the tumor sample has been determined to have a detectable expression level of PD-L1 in greater than, or equal to, 50% of the tumor cells in the tumor sample.

### Claim 155 (depends on 150, 151, 152, 153, 154)

The anti-TIGIT antagonist antibody and anti-PD-L1 antagonist antibody for use of any one of claims 150-154, wherein the tumor sample has been determined to have a detectable expression level of PD-L1 in tumor-infiltrating immune cells that comprise greater than, or equal to, 1% of the tumor sample.

### Claim 156 (depends on 155)

The anti-TIGIT antagonist antibody and anti-PD-L1 antagonist antibody for use of claim 155, wherein the tumor sample has been determined to have a detectable expression level of PD-L1 in tumor-infiltrating immune cells that comprise greater than, or equal to, 1% and less than 5% of the tumor sample.

### Claim 157 (depends on 155)

The anti-TIGIT antagonist antibody and anti-PD-L1 antagonist antibody for use of claim 155, wherein the tumor sample has been determined to have a detectable expression level of PD-L1 in tumor-infiltrating immune cells that comprise greater than, or equal to, 5% and less than 10% of the tumor sample.

### Claim 158 (depends on 155)

The anti-TIGIT antagonist antibody and anti-PD-L1 antagonist antibody for use of claim 155, wherein the tumor sample has been determined to have a detectable expression level of PD-L1 in tumor-infiltrating immune cells that comprise greater than, or equal to, 10% of the tumor sample.

### Claim 159 (depends on 142)

The anti-TIGIT antagonist antibody and anti-PD-L1 antagonist antibody for use of claim 142, wherein the detectable expression level of PD-L1 is a detectable nucleic acid expression level of PD-L1.

### Claim 160 (depends on 159)

The anti-TIGIT antagonist antibody and anti-PD-L1 antagonist antibody for use of claim 159, wherein the detectable nucleic acid expression level of PD-L1 has been determined by RNA-seq, RT-qPCR, qPCR, multiplex qPCR or RT-qPCR, microarray analysis, SAGE, MassARRAY technique, ISH, or a combination thereof.

### Claim 161 (depends on 100, 101, 102, 103, 104, 105, 106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 118, 119, 120, 121, 122, 123, 124, 125, 126, 127, 128, 129, 130, 131, 132, 133, 134, 135, 136, 137, 138, 139, 140, 141, 142, 143, 144, 145, 146, 147, 148, 149, 150, 151, 152, 153, 154, 155, 156, 157, 158, 159, 160)

The anti-TIGIT antagonist antibody and anti-PD-L1 antagonist antibody for use of any one of claims 100-160, wherein the lung cancer is a non-small cell lung cancer (NSCLC).

### Claim 162 (depends on 161)

The anti-TIGIT antagonist antibody and anti-PD-L1 antagonist antibody for use of claim 161, wherein the NSCLC is a squamous NSCLC.

### Claim 163 (depends on 161)

The anti-TIGIT antagonist antibody and anti-PD-L1 antagonist antibody for use of claim 161, wherein the NSCLC is a non-squamous NSCLC.

### Claim 164 (depends on 161, 162, 163)

The anti-TIGIT antagonist antibody and anti-PD-L1 antagonist antibody for use of any one of claims 161-163, wherein the NSCLC is a locally advanced unresectable NSCLC.

### Claim 165 (depends on 164)

The anti-TIGIT antagonist antibody and anti-PD-L1 antagonist antibody for use of claim 164, wherein the NSCLC is a Stage IIIB NSCLC.

### Claim 166 (depends on 161, 162, 163)

The anti-TIGIT antagonist antibody and anti-PD-L1 antagonist antibody for use of any one of claims 161-163, wherein the NSCLC is a recurrent or metastatic NSCLC.

### Claim 167 (depends on 166)

The anti-TIGIT antagonist antibody and anti-PD-L1 antagonist antibody for use of claim 166, wherein the NSCLC is a Stage IV NSCLC.

### Claim 168 (depends on 166, 167)

The anti-TIGIT antagonist antibody and anti-PD-L1 antagonist antibody for use of claim 166 or 167, wherein the subject has not been previously treated for Stage IV NSCLC.

### Claim 169 (depends on 100, 101, 102, 103, 104, 105, 106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 118, 119, 120, 121, 122, 123, 124, 125, 126, 127, 128, 129, 130, 131, 132, 133, 134, 135, 136, 137, 138, 139, 140, 141, 142, 143, 144, 145, 146, 147, 148, 149, 150, 151, 152, 153, 154, 155, 156, 157, 158, 159, 160, 161, 162, 163, 164, 165, 166, 167, 168)

The anti-TIGIT antagonist antibody and anti-PD-L1 antagonist antibody for use of any one of claims 100-168, wherein the subject does not have a sensitizing epidermal growth factor receptor (EGFR) gene mutation or anaplastic lymphoma kinase (ALK) gene rearrangement.

### Claim 170 (depends on 100, 101, 102, 103, 104, 105, 106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 118, 119, 120, 121, 122, 123, 124, 125, 126, 127, 128, 129, 130, 131, 132, 133, 134, 135, 136, 137, 138, 139, 140, 141, 142, 143, 144, 145, 146, 147, 148, 149, 150, 151, 152, 153, 154, 155, 156, 157, 158, 159, 160, 161, 162, 163, 164, 165, 166, 167, 168, 169)

The anti-TIGIT antagonist antibody and anti-PD-L1 antagonist antibody for use of any one of claims 100-169, wherein the subject does not have a pulmonary lymphoepithelioma-like carcinoma subtype of NSCLC.

### Claim 171 (depends on 100, 101, 102, 103, 104, 105, 106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 118, 119, 120, 121, 122, 123, 124, 125, 126, 127, 128, 129, 130, 131, 132, 133, 134, 135, 136, 137, 138, 139, 140, 141, 142, 143, 144, 145, 146, 147, 148, 149, 150, 151, 152, 153, 154, 155, 156, 157, 158, 159, 160, 161, 162, 163, 164, 165, 166, 167, 168, 169, 170)

The anti-TIGIT antagonist antibody and anti-PD-L1 antagonist antibody for use of any one of claims 100-170, wherein the subject does not have an active EBV infection or a known or suspected chronic active EBV infection.

### Claim 172 (depends on 100, 101, 102, 103, 104, 105, 106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 118, 119, 120, 121, 122, 123, 124, 125, 126, 127, 128, 129, 130, 131, 132, 133, 134, 135, 136, 137, 138, 139, 140, 141, 142, 143, 144, 145, 146, 147, 148, 149, 150, 151, 152, 153, 154, 155, 156, 157, 158, 159, 160, 161, 162, 163, 164, 165, 166, 167, 168, 169, 170, 171)

The anti-TIGIT antagonist antibody and anti-PD-L1 antagonist antibody for use of any one of claims 100-171, wherein the subject is negative for EBV IgM or negative by EBV PCR.

### Claim 173 (depends on 172)

The anti-TIGIT antagonist antibody and anti-PD-L1 antagonist antibody for use of claim 172, wherein the subject is negative for EBV IgM and negative by EBV PCR.

### Claim 174 (depends on 172, 173)

The anti-TIGIT antagonist antibody and anti-PD-L1 antagonist antibody for use of claim 172 or 173, wherein the subject is positive for EBV IgG or positive for EBNA.

### Claim 175 (depends on 174)

The anti-TIGIT antagonist antibody and anti-PD-L1 antagonist antibody for use of claim 174, wherein the subject is positive for EBV IgG and positive for EBNA.

### Claim 176 (depends on 100, 101, 102, 103, 104, 105, 106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 118, 119, 120, 121, 122, 123, 124, 125, 126, 127, 128, 129, 130, 131, 132, 133, 134, 135, 136, 137, 138, 139, 140, 141, 142, 143, 144, 145, 146, 147, 148, 149, 150, 151, 152, 153, 154, 155, 156, 157, 158, 159, 160, 161, 162, 163, 164, 165, 166, 167, 168, 169, 170, 171, 172, 173)

The anti-TIGIT antagonist antibody and anti-PD-L1 antagonist antibody for use of any one of claims 100-173, wherein the subject is negative for EBV IgG or negative for EBNA.

### Claim 177 (depends on 176)

The anti-TIGIT antagonist antibody and anti-PD-L1 antagonist antibody for use of claim 176, wherein the subject is negative for EBV IgG and negative for EBNA.

### Claim 178 (depends on 100, 101, 102, 103, 104, 105, 106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 118, 119, 120, 121, 122, 123, 124, 125, 126, 127, 128, 129, 130, 131, 132, 133, 134, 135, 136, 137, 138, 139, 140, 141, 142, 143, 144, 145, 146, 147, 148, 149, 150, 151, 152, 153, 154, 155, 156, 157, 158, 159, 160, 161, 162, 163, 164, 165, 166, 167, 168, 169, 170, 171, 172, 173, 174, 175, 176, 177)

The anti-TIGIT antagonist antibody and anti-PD-L1 antagonist antibody for use of any one of claims 100-177, wherein administration of the anti-TIGIT antagonist antibody and anti-PD-L1 antagonist antibody results in a clinical response.

### Claim 179 (depends on 178)

The anti-TIGIT antagonist antibody and anti-PD-L1 antagonist antibody for use of claim 178, wherein the clinical response is an increase in the objective response rate (ORR) of the subject as compared to a reference ORR.

### Claim 180 (depends on 179)

The anti-TIGIT antagonist antibody and anti-PD-L1 antagonist antibody for use of claim 179, wherein the reference ORR is the median ORR of a population of subjects who have received a treatment comprising an anti-PD-L1 antagonist antibody without an anti-TIGIT antagonist antibody.

### Claim 181 (depends on 178, 179, 180)

The anti-TIGIT antagonist antibody and anti-PD-L1 antagonist antibody for use of any one of claims 178-180, wherein the clinical response is an increase in the progression-free survival (PFS) of the subject as compared to a reference PFS time.

### Claim 182 (depends on 178, 179, 180, 181)

The anti-TIGIT antagonist antibody and anti-PD-L1 antagonist antibody for use of any one of claims 178-181, wherein the reference PFS time is the median PFS time of a population of subjects who have received a treatment comprising an anti-PD-L1 antagonist antibody without an anti-TIGIT antagonist antibody.

### Claim 183

An anti-TIGIT antagonist antibody and atezolizumab for use in a method of treating a subject having a NSCLC, wherein the method comprises administering to the subject one or more dosing cycles of an anti-TIGIT antagonist antibody at a fixed dose of 600 mg every three weeks and atezolizumab at a fixed dose of 1200 mg every three weeks, wherein the anti-TIGIT antagonist antibody comprises:
a VH domain comprising the amino acid sequence of SEQ ID NO: 17 or 18; and
a VL domain comprising the amino acid sequence of SEQ ID NO: 19.

### Claim 184

Tiragolumab and atezolizumab for use in a method of treating a subject having a NSCLC, wherein the method comprises administering to the subject one or more dosing cycles of tiragolumab at a fixed dose of 600 mg every three weeks and atezolizumab at a fixed dose of 1200 mg every three weeks.

### Claim 185

Use of an anti-TIGIT antagonist antibody and an anti-PD-L1 antagonist antibody in the manufacture of a medicament for use in a method of treating a subject having a lung cancer, wherein the method comprises administering to the subject one or more dosing cycles of the medicament, and wherein the medicament is formulated for administration of the anti-TIGIT antagonist antibody at a fixed dose of between about 30 mg to about 1200 mg every three weeks and the anti-PD-L1 antagonist antibody at a fixed dose of between about 80 mg to about 1600 mg every three weeks.

### Claim 186

Use of an anti-TIGIT antagonist antibody in the manufacture of a medicament for use in a method of treating a subject having a lung cancer, wherein the method comprises administering to the subject one or more dosing cycles of the medicament and an anti-PD-L1 antagonist antibody, and wherein the medicament is formulated for administration of the anti-TIGIT antagonist antibody at a fixed dose of between about 30 mg to about 1200 mg every three weeks and the anti-PD-L1 antagonist antibody is to be administered at a fixed dose of between about 80 mg to about 1600 mg every three weeks.

### Claim 187

Use of an anti-PD-L1 antagonist antibody in the manufacture of a medicament for use in a method of treating a subject having a lung cancer, wherein the method comprises administering to the subject one or more dosing cycles of the medicament and an anti-TIGIT antagonist antibody, and wherein the medicament is formulated for administration of the anti-PD-L1 antagonist antibody at a fixed dose of between about 80 mg to about 1600 mg every three weeks and the anti-TIGIT antagonist antibody is to be administered at a fixed dose of between about 30 mg to about 1200 mg every three weeks.

### Claim 188 (depends on 185, 186, 187)

The use of any one of claims 185-187, wherein the anti-TIGIT antagonist antibody is to be administered to the subject at a fixed dose of between about 30 mg to about 600 mg every three weeks.

### Claim 189 (depends on 188)

The use of claim 188, wherein the anti-TIGIT antagonist antibody is to be administered to the subject at a fixed dose of about 600 mg every three weeks.

### Claim 190 (depends on 185, 186, 187, 188, 189)

The use of any one of claims 185-189, wherein the anti-TIGIT antagonist antibody comprises the following hypervariable regions (HVRs):
an HVR-H1 sequence comprising the amino acid sequence of SNSAAWN (SEQ ID NO: 1);
an HVR-H2 sequence comprising the amino acid sequence of KTYYRFKWYSDYAVSVKG (SEQ ID NO: 2);
an HVR-H3 sequence comprising the amino acid sequence of ESTTYDLLAGPFDY (SEQ ID NO: 3);
an HVR-L1 sequence comprising the amino acid sequence of KSSQTVLYSSNNKKYLA (SEQ ID NO: 4);
an HVR-L2 sequence comprising the amino acid sequence of WASTRES (SEQ ID NO: 5); and
an HVR-L3 sequence comprising the amino acid sequence of QQYYSTPFT (SEQ ID NO: 6).

### Claim 191 (depends on 190)

The use of claim 190, wherein the anti-TIGIT antagonist antibody further comprises the following light chain variable region framework regions (FRs):
an FR-L1 comprising the amino acid sequence of DIVMTQSPDSLAVSLGERATINC (SEQ ID NO: 7);
an FR-L2 comprising the amino acid sequence of WYQQKPGQPPNLLIY (SEQ ID NO: 8);
an FR-L3 comprising the amino acid sequence of GVPDRFSGSGSGTDFTLTISSLQAEDVAVYYC (SEQ ID NO: 9); and
an FR-L4 comprising the amino acid sequence of FGPGTKVEIK (SEQ ID NO: 10).

### Claim 192 (depends on 190)

The use of claim 190, wherein the anti-TIGIT antagonist antibody further comprises the following heavy chain variable region FRs:
an FR-H1 comprising the amino acid sequence of X1VQLQQSGPGLVKPSQTLSLTCAISGDSVS (SEQ ID NO: 11), wherein X1 is Q or E;
an FR-H2 comprising the amino acid sequence of WIRQSPSRGLEWLG (SEQ ID NO: 12);
an FR-H3 comprising the amino acid sequence of RITINPDTSKNQFSLQLNSVTPEDTAVFYCTR (SEQ ID NO: 13); and
an FR-H4 comprising the amino acid sequence of WGQGTLVTVSS (SEQ ID NO: 14).

### Claim 193 (depends on 192)

The use of claim 192, wherein X1 is Q.

### Claim 194 (depends on 192)

The use of claim 192, wherein X1 is E.

### Claim 195 (depends on 190, 191, 192, 193, 194)

The use of any one of claims 190-194, wherein the anti-TIGIT antagonist antibody comprises:
(a) a heavy chain variable (VH) domain comprising an amino acid sequence having at least 95% sequence identity to the amino acid sequence of SEQ ID NO: 17 or 18;
(b) a light chain variable (VL) domain comprising an amino acid sequence having at least 95% sequence identity to the amino acid sequence of SEQ ID NO: 19; or
(c) a VH domain as in (a) and a VL domain as in (b).

### Claim 196 (depends on 185, 186, 187, 188, 189, 190, 191, 192, 193, 194, 195)

The use of any one of claims 185-195, wherein the anti-TIGIT antagonist antibody comprises:
(a) a heavy chain variable (VH) domain comprising an amino acid sequence having at least 95% sequence identity to the amino acid sequence of SEQ ID NO: 17 or 18;
(b) a light chain variable (VL) domain comprising an amino acid sequence having at least 95% sequence identity to the amino acid sequence of SEQ ID NO: 19; or
(c) a VH domain as in (a) and a VL domain as in (b).

### Claim 197 (depends on 185, 186, 187, 188, 189, 190, 191, 192, 193, 194, 195, 196)

The use of any one of claims 185-196, wherein the anti-TIGIT antagonist antibody is a monoclonal antibody.

### Claim 198 (depends on 197)

The use of claim 197, wherein the anti-TIGIT antagonist antibody is a human antibody.

### Claim 199 (depends on 185, 186, 187, 188, 189, 190, 191, 192, 193, 194, 195, 196, 197, 198)

The use of any one of claims 185-198, wherein the anti-TIGIT antagonist antibody is a full-length antibody.

### Claim 200 (depends on 185, 186, 187, 188, 189, 190, 191, 192, 194, 195, 196, 197, 198, 199)

The use of any one of claims 185-192 and 194-199, wherein the anti-TIGIT antagonist antibody is tiragolumab.

### Claim 201 (depends on 185, 186, 187, 188, 189, 190, 191, 192, 193, 194, 195, 196, 197, 198)

The use of any one of claims 185-198, wherein the anti-TIGIT antagonist antibody is an antibody fragment that binds TIGIT selected from the group consisting of Fab, Fab′, Fab′-SH, Fv, single chain variable fragment (scFv), and (Fab′)2 fragments.

### Claim 202 (depends on 185, 186, 187, 188, 189, 190, 191, 192, 193, 194, 195, 196, 197, 198, 199, 200, 201)

The use of any one of claims 185-201, wherein the anti-TIGIT antagonist antibody is an IgG class antibody.

### Claim 203 (depends on 202)

The use of claim 202, wherein the IgG class antibody is an IgG1 subclass antibody.

### Claim 204 (depends on 185, 186, 187, 188, 189, 190, 191, 192, 193, 194, 195, 196, 197, 198, 199, 200, 201, 202, 203)

The use of any one of claims 185-203, wherein the anti-PD-L1 antagonist antibody is to be administered to the subject at a fixed dose of about 1200 mg every three weeks.

### Claim 205 (depends on 185, 186, 187, 188, 189, 190, 191, 192, 193, 194, 195, 196, 197, 198, 199, 200, 201, 202, 203, 204)

The use of any one of claims 185-204, wherein the anti-PD-L1 antagonist antibody is atezolizumab (MPDL3280A), YW243.55.S70, MSB0010718C, MDX-1105, or MEDI4736.

### Claim 206 (depends on 205)

The use of claim 205, wherein the anti-PD-L1 antagonist antibody is atezolizumab.

### Claim 207 (depends on 185, 186, 187, 188, 189, 190, 191, 192, 193, 194, 195, 196, 197, 198, 199, 200, 201, 202, 203, 204)

The use of any one of claims 185-204, wherein the anti-PD-L1 antagonist antibody comprises the following HVRs:
an HVR-H1 sequence comprising the amino acid sequence of GFTFSDSWIH (SEQ ID NO: 20);
an HVR-H2 sequence comprising the amino acid sequence of AWISPYGGSTYYADSVKG (SEQ ID NO: 21);
an HVR-H3 sequence comprising the amino acid sequence of RHWPGGFDY (SEQ ID NO: 22);
an HVR-L1 sequence comprising the amino acid sequence of RASQDVSTAVA (SEQ ID NO: 23);
an HVR-L2 sequence comprising the amino acid sequence of SASFLYS (SEQ ID NO: 24); and
an HVR-L3 sequence comprising the amino acid sequence of QQYLYHPAT (SEQ ID NO: 25).

### Claim 208 (depends on 207)

The use of claim 207, wherein the anti-PD-L1 antagonist antibody comprises:
(a) a heavy chain variable (VH) domain comprising an amino acid sequence having at least 95% sequence identity to the amino acid sequence of SEQ ID NO: 26;
(b) a light chain variable (VL) domain comprising an amino acid sequence having at least 95% sequence identity to the amino acid sequence of SEQ ID NO: 27; or
(c) a VH domain as in (a) and a VL domain as in (b).

### Claim 209 (depends on 185, 186, 187, 188, 189, 190, 191, 192, 193, 194, 195, 196, 197, 198, 199, 200, 201, 202, 203, 204, 205, 206, 207, 208)

The use of any one of claims 185-208, wherein the anti-PD-L1 antagonist antibody comprises:
a VH domain comprising the amino acid sequence of SEQ ID NO: 26; and
a VL domain comprising the amino acid sequence of SEQ ID NO: 27.

### Claim 210 (depends on 207, 208, 209)

The use of any one of claims 207-209, wherein the anti-PD-L1 antagonist antibody is a monoclonal antibody.

### Claim 211 (depends on 210)

The use of claim 210, wherein the anti-PD-L1 antagonist antibody is a humanized antibody.

### Claim 212 (depends on 210, 211)

The use of claim 210 or 211, wherein the anti-PD-L1 antagonist antibody is a full-length antibody.

### Claim 213 (depends on 207, 208, 209, 210, 211)

The use of any one of claims 207-211, wherein the anti-PD-L1 antagonist antibody is an antibody fragment that binds PD-L1 selected from the group consisting of Fab, Fab′, Fab′-SH, Fv, single chain variable fragment (scFv), and (Fab′)2 fragments.

### Claim 214 (depends on 207, 208, 209, 210, 211, 212, 213)

The use of any one of claims 207-213, wherein the anti-PD-L1 antagonist antibody is an IgG class antibody.

### Claim 215 (depends on 214)

The use of claim 214, wherein the IgG class antibody is an IgG1 subclass antibody.

### Claim 216 (depends on 185, 186, 187, 188, 189, 190, 191, 192, 193, 194, 195, 196, 197, 198, 199, 200, 201, 202, 203, 204, 205, 206, 207, 208, 209, 210, 211, 212, 213, 214, 215)

The use of any one of claims 185-215, wherein the anti-TIGIT antagonist antibody is to be administered to the subject at a fixed dose of about 600 mg of every three weeks and the anti-PD-L1 antagonist antibody is to be administered to the subject at a fixed dose of about 1200 mg every three weeks.

### Claim 217 (depends on 185, 186, 187, 188, 189, 190, 191, 192, 193, 194, 195, 196, 197, 198, 199, 200, 201, 202, 203, 204, 205, 206, 207, 208, 209, 210, 211, 212, 213, 214, 215, 216)

The use of any one of claims 185-216, wherein the length of each of the one or more dosing cycles is 21 days.

### Claim 218 (depends on 185, 186, 187, 188, 189, 190, 191, 192, 193, 194, 195, 196, 197, 198, 199, 200, 201, 202, 203, 204, 205, 206, 207, 208, 209, 210, 211, 212, 213, 214, 215, 216, 217)

The use of any one of claims 185-217, wherein the anti-TIGIT antagonist antibody and anti-PD-L1 antagonist antibody are to be administered to the subject on about Day 1 of each of the one or more dosing cycles.

### Claim 219 (depends on 185, 186, 187, 188, 189, 190, 191, 192, 193, 194, 195, 196, 197, 198, 199, 200, 201, 202, 203, 204, 205, 206, 207, 208, 209, 210, 211, 212, 213, 214, 215, 216, 217, 218)

The use of any one of claims 185-218, wherein the anti-TIGIT antagonist antibody is to be administered to the subject before the anti-PD-L1 antagonist antibody.

### Claim 220 (depends on 219)

The use of claim 219, wherein a first observation period is to follow administration of the anti-TIGIT antagonist antibody and second observation period is to follow administration of the anti-PD-L1 antagonist antibody.

### Claim 221 (depends on 220)

The use of claim 220, wherein the first observation period and the second observation period are each between about 30 minutes to about 60 minutes in length.

### Claim 222 (depends on 185, 186, 187, 188, 189, 190, 191, 192, 193, 194, 195, 196, 197, 198, 199, 200, 201, 202, 203, 204, 205, 206, 207, 208, 209, 210, 211, 212, 213, 214, 215, 216, 217, 218)

The use of any one of claims 185-218, wherein the anti-PD-L1 antagonist antibody is to be administered to the subject before the anti-TIGIT antagonist antibody.

### Claim 223 (depends on 222)

The use of claim 222, wherein a first observation period is to follow administration of the anti-PD-L1 antagonist antibody and second observation period is to follow administration of the anti-TIGIT antagonist antibody.

### Claim 224 (depends on 223)

The use of claim 223, wherein the first observation period and the second observation period are each between about 30 minutes to about 60 minutes in length.

### Claim 225 (depends on 185, 186, 187, 188, 189, 190, 191, 192, 193, 194, 195, 196, 197, 198, 199, 200, 201, 202, 203, 204, 205, 206, 207, 208, 209, 210, 211, 212, 213, 214, 215, 216, 217, 218)

The use of any one of claims 185-218, wherein the anti-TIGIT antagonist antibody is to be administered to the subject simultaneously with the anti-PD-L1 antagonist antibody.

### Claim 226 (depends on 185, 186, 187, 188, 189, 190, 191, 192, 193, 194, 195, 196, 197, 198, 199, 200, 201, 202, 203, 204, 205, 206, 207, 208, 209, 210, 211, 212, 213, 214, 215, 216, 217, 218, 219, 220, 221, 222, 223, 224, 225)

The use of any one of claims 185-225, wherein the anti-TIGIT antagonist antibody and anti-PD-L1 antagonist antibody are to be administered to the subject intravenously.

### Claim 227 (depends on 226)

The use of claim 226, wherein the anti-TIGIT antagonist antibody is to be administered to the subject by intravenous infusion over 60±10 minutes.

### Claim 228 (depends on 226, 227)

The use of claim 226 or 227, wherein the anti-PD-L1 antagonist antibody is to be administered to the subject by intravenous infusion over 60±15 minutes.

### Claim 229 (depends on 185, 186, 187, 188, 189, 190, 191, 192, 193, 194, 195, 196, 197, 198, 199, 200, 201, 202, 203, 204, 205, 206, 207, 208, 209, 210, 211, 212, 213, 214, 215, 216, 217, 218, 219, 220, 221, 222, 223, 224, 225, 226, 227, 228)

The use of any one of claims 185-228, wherein a tumor sample obtained from the subject has been determined to have a detectable expression level of PD-L1.

### Claim 230 (depends on 229)

The use of claim 229, wherein the detectable expression level of PD-L1 is a detectable protein expression level of PD-L1.

### Claim 231 (depends on 230)

The use of claim 230, wherein the detectable protein expression level of PD-L1 has been determined by an immunohistochemical (IHC) assay.

### Claim 232 (depends on 231)

The use of claim 231, wherein the IHC assay uses anti-PD-L1 antibody 22C3, SP142, SP263, or 28-8.

### Claim 233 (depends on 232)

The use of claim 232, wherein the IHC assay uses anti-PD-L1 antibody 22C3.

### Claim 234 (depends on 233)

The use of claim 233, wherein the tumor sample has been determined to have a tumor proportion score (TPS) of greater than, or equal to, 1%.

### Claim 235 (depends on 234)

The use of claim 234, wherein the TPS is greater than, or equal to, 1% and less than 50%.

### Claim 236 (depends on 234)

The use of claim 234, wherein the TPS is greater than, or equal to, 50%.

### Claim 237 (depends on 232)

The use of claim 232, wherein the IHC assay uses anti-PD-L1 antibody SP142.

### Claim 238 (depends on 237)

The use of claim 237, wherein the tumor sample has been determined to have a detectable expression level of PD-L1 in greater than, or equal to, 1% of the tumor cells in the tumor sample.

### Claim 239 (depends on 238)

The use of claim 238, wherein the tumor sample has been determined to have a detectable expression level of PD-L1 in greater than, or equal to, 1% and less than 5% of the tumor cells in the tumor sample.

### Claim 240 (depends on 238)

The use of claim 238, wherein the tumor sample has been determined to have a detectable expression level of PD-L1 in greater than, or equal to, 5% and less than 50% of the tumor cells in the tumor sample.

### Claim 241 (depends on 238)

The use of claim 238, wherein the tumor sample has been determined to have a detectable expression level of PD-L1 in greater than, or equal to, 50% of the tumor cells in the tumor sample.

### Claim 242 (depends on 237, 238, 239, 240, 241)

The use of any one of claims 237-241, wherein the tumor sample has been determined to have a detectable expression level of PD-L1 in tumor-infiltrating immune cells that comprise greater than, or equal to, 1% of the tumor sample.

### Claim 243 (depends on 242)

The use of claim 242, wherein the tumor sample has been determined to have a detectable expression level of PD-L1 in tumor-infiltrating immune cells that comprise greater than, or equal to, 1% and less than 5% of the tumor sample.

### Claim 244 (depends on 242)

The use of claim 242, wherein the tumor sample has been determined to have a detectable expression level of PD-L1 in tumor-infiltrating immune cells that comprise greater than, or equal to, 5% and less than 10% of the tumor sample.

### Claim 245 (depends on 242)

The use of claim 242, wherein the tumor sample has been determined to have a detectable expression level of PD-L1 in tumor-infiltrating immune cells that comprise greater than, or equal to, 10% of the tumor sample.

### Claim 246 (depends on 229)

The use of claim 229, wherein the detectable expression level of PD-L1 is a detectable nucleic acid expression level of PD-L1.

### Claim 247 (depends on 246)

The use of claim 246, wherein the detectable nucleic acid expression level of PD-L1 has been determined by RNA-seq, RT-qPCR, qPCR, multiplex qPCR or RT-qPCR, microarray analysis, SAGE, MassARRAY technique, ISH, or a combination thereof.

### Claim 248 (depends on 185, 186, 187, 188, 189, 190, 191, 192, 193, 194, 195, 196, 197, 198, 199, 200, 201, 202, 203, 204, 205, 206, 207, 208, 209, 210, 211, 212, 213, 214, 215, 216, 217, 218, 219, 220, 221, 222, 223, 224, 225, 226, 227, 228, 229, 230, 231, 232, 233, 234, 235, 236, 237, 238, 239, 240, 241, 242, 243, 244, 245, 246, 247)

The use of any one of claims 185-247, wherein the lung cancer is a non-small cell lung cancer (NSCLC).

### Claim 249 (depends on 248)

The use of claim 248, wherein the NSCLC is a squamous NSCLC.

### Claim 250 (depends on 248)

The use of claim 248, wherein the NSCLC is a non-squamous NSCLC.

### Claim 251 (depends on 248, 249, 250)

The use of any one of claims 248-250, wherein the NSCLC is a locally advanced unresectable NSCLC.

### Claim 252 (depends on 251)

The use of claim 251, wherein the NSCLC is a Stage IIIB NSCLC.

### Claim 253 (depends on 248, 249, 250, 251)

The use of any one of claims 248-251, wherein the NSCLC is a recurrent or metastatic NSCLC.

### Claim 254 (depends on 253)

The use of claim 253, wherein the NSCLC is a Stage IV NSCLC.

### Claim 255 (depends on 253, 254)

The use of claim 253 or 254, wherein the subject has not been previously treated for Stage IV NSCLC.

### Claim 256 (depends on 185, 186, 187, 188, 189, 190, 191, 192, 193, 194, 195, 196, 197, 198, 199, 200, 201, 202, 203, 204, 205, 206, 207, 208, 209, 210, 211, 212, 213, 214, 215, 216, 217, 218, 219, 220, 221, 222, 223, 224, 225, 226, 227, 228, 229, 230, 231, 232, 233, 234, 235, 236, 237, 238, 239, 240, 241, 242, 243, 244, 245, 246, 247, 248, 249, 250, 251, 252, 253, 254, 255)

The use of any one of claims 185-255, wherein the subject does not have a sensitizing epidermal growth factor receptor (EGFR) gene mutation or anaplastic lymphoma kinase (ALK) gene rearrangement.

### Claim 257 (depends on 185, 186, 187, 188, 189, 190, 191, 192, 193, 194, 195, 196, 197, 198, 199, 200, 201, 202, 203, 204, 205, 206, 207, 208, 209, 210, 211, 212, 213, 214, 215, 216, 217, 218, 219, 220, 221, 222, 223, 224, 225, 226, 227, 228, 229, 230, 231, 232, 233, 234, 235, 236, 237, 238, 239, 240, 241, 242, 243, 244, 245, 246, 247, 248, 249, 250, 251, 252, 253, 254, 255, 256)

The use of any one of claims 185-256, wherein the subject does not have a pulmonary lymphoepithelioma-like carcinoma subtype of NSCLC.

### Claim 258 (depends on 185, 186, 187, 188, 189, 190, 191, 192, 193, 194, 195, 196, 197, 198, 199, 200, 201, 202, 203, 204, 205, 206, 207, 208, 209, 210, 211, 212, 213, 214, 215, 216, 217, 218, 219, 220, 221, 222, 223, 224, 225, 226, 227, 228, 229, 230, 231, 232, 233, 234, 235, 236, 237, 238, 239, 240, 241, 242, 243, 244, 245, 246, 247, 248, 249, 250, 251, 252, 253, 254, 255, 256, 257)

The use of any one of claims 185-257, wherein the subject does not have an active EBV infection or a known or suspected chronic active EBV infection.

### Claim 259 (depends on 185, 186, 187, 188, 189, 190, 191, 192, 193, 194, 195, 196, 197, 198, 199, 200, 201, 202, 203, 204, 205, 206, 207, 208, 209, 210, 211, 212, 213, 214, 215, 216, 217, 218, 219, 220, 221, 222, 223, 224, 225, 226, 227, 228, 229, 230, 231, 232, 233, 234, 235, 236, 237, 238, 239, 240, 241, 242, 243, 244, 245, 246, 247, 248, 249, 250, 251, 252, 253, 254, 255, 256, 257, 258)

The use of any one of claims 185-258, wherein the subject is negative for EBV IgM or negative by EBV PCR.

### Claim 260 (depends on 259)

The use of claim 259, wherein the subject is negative for EBV IgM and negative by EBV PCR.

### Claim 261 (depends on 259, 260)

The use of claim 259 or 260, wherein the subject is positive for EBV IgG or positive for EBNA.

### Claim 262 (depends on 261)

The use of claim 261, wherein the subject is positive for EBV IgG and positive for EBNA.

### Claim 263 (depends on 185, 186, 187, 188, 189, 190, 191, 192, 193, 194, 195, 196, 197, 198, 199, 200, 201, 202, 203, 204, 205, 206, 207, 208, 209, 210, 211, 212, 213, 214, 215, 216, 217, 218, 219, 220, 221, 222, 223, 224, 225, 226, 227, 228, 229, 230, 231, 232, 233, 234, 235, 236, 237, 238, 239, 240, 241, 242, 243, 244, 245, 246, 247, 248, 249, 250, 251, 252, 253, 254, 255, 256, 257, 258, 259, 260, 261, 262)

The use of any one of claims 185-262, wherein the subject is negative for EBV IgG or negative for EBNA.

### Claim 264 (depends on 263)

The use of claim 263, wherein the subject is negative for EBV IgG and negative for EBNA.

### Claim 265 (depends on 185, 186, 187, 188, 189, 190, 191, 192, 193, 194, 195, 196, 197, 198, 199, 200, 201, 202, 203, 204, 205, 206, 207, 208, 209, 210, 211, 212, 213, 214, 215, 216, 217, 218, 219, 220, 221, 222, 223, 224, 225, 226, 227, 228, 229, 230, 231, 232, 233, 234, 235, 236, 237, 238, 239, 240, 241, 242, 243, 244, 245, 246, 247, 248, 249, 250, 251, 252, 253, 254, 255, 256, 257, 258, 259, 260, 261, 262, 263, 264)

The use of any one of claims 185-264, wherein administration of the anti-TIGIT antagonist antibody and anti-PD-L1 antagonist antibody results in a clinical response.

### Claim 266 (depends on 265)

The use of claim 265, wherein the clinical response is an increase in the objective response rate (ORR) of the subject as compared to a reference ORR.

### Claim 267 (depends on 266)

The use of claim 266, wherein the reference ORR is the median ORR of a population of subjects who have received a treatment comprising an anti-PD-L1 antagonist antibody without an anti-TIGIT antagonist antibody.

### Claim 268 (depends on 265, 266, 267)

The use of any one of claims 265-267, wherein the clinical response is an increase in the progression-free survival (PFS) of the subject as compared to a reference PFS time.

### Claim 269 (depends on 265, 266, 267, 268)

The use of any one of claims 265-268, wherein the reference PFS time is the median PFS time of a population of subjects who have received a treatment comprising an anti-PD-L1 antagonist antibody without an anti-TIGIT antagonist antibody.

### Claim 270

Use of an anti-TIGIT antagonist antibody and atezolizumab in the manufacture of a medicament for use in a method of treating a subject having a NSCLC, wherein the method comprises administering to the subject one or more dosing cycles of the medicament, and wherein the medicament is formulated for administration of the anti-TIGIT antagonist antibody at a fixed dose of 600 mg every three weeks and atezolizumab at a fixed dose of 1200 mg every three weeks, and wherein the anti-TIGIT antagonist antibody comprises:
a VH domain comprising the amino acid sequence of SEQ ID NO: 17 or 18; and
a VL domain comprising the amino acid sequence of SEQ ID NO: 19.

### Claim 271

Use of tiragolumab and atezolizumab in the manufacture of a medicament for use in a method of treating a subject having a NSCLC, wherein the method comprises administering to the subject one or more dosing cycles of the medicament, and wherein the medicament is formulated for administration of tiragolumab at a fixed dose of 600 mg every three weeks and atezolizumab at a fixed dose of 1200 mg every three weeks.

### Claim 272 (depends on 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 192, 193, 194)

A kit comprising an anti-TIGIT antagonist antibody, an anti-PD-L1 antagonist antibody, and a package insert comprising instructions to administer the anti-TIGIT antagonist antibody and the anti-PD-L1 antagonist antibody to a subject having a lung cancer in accordance with the methods of any one of claims 1-86 and 192-194.