Dosing for treatment with anti-tigit and anti-pd-l1 antagonist antibodies
AssigneeGenentech, Inc.
InventorsRaymond D. MENG, Sean Keith KELLEY, Namrata Srivastava PATIL
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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.
Claims272
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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%.
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%.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
Dependencies are inferred from the claim text.