Methods and compositions for treating cancer
AssigneesGenentech, Inc., Chugai Seiyaku Kabushiki Kaisha
InventorsColby Sasson SHEMESH, David VOONG, Yulei WANG, Eunpi CHO, Stevan Nicholas DJAKOVIC, Eisuke UEDA, Takaaki ISHIDA
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Abstract
The invention provides methods and compositions for treating cancer (e.g., a locally advanced, recurrent, or metastatic solid tumor) in a subject, for example, by administering an anti-cancer therapy that includes an anti-latent TGF-beta 1 antibody to the subject. Also provided are compositions (e.g., an anti-latent TGF-beta 1 antibody, pharmaceutical compositions thereof, kits thereof, and articles of manufacture thereof) for use in treating cancer in a subject.
Claims187
A method of treating a subject having a locally advanced, recurrent, or metastatic solid tumor, the method comprising administering to the subject an anti-cancer therapy comprising an anti-latent transforming growth factor (TGF)-beta 1 antibody at a dosage of 1800 mg, wherein the anti-latent TGF-beta 1 antibody comprises the following six hypervariable regions (HVRs):
- (a) HVR-H1, HVR-H2, and HVR-H3 comprising the amino acid sequences of SEQ ID NO:
- 1, 2, and 3, respectively, and HVR-L1, HVR-L2, and HVR-L3 comprising the amino acid sequences of SEQ ID NO:
- 4, 5, and 6, respectively;
- (b) HVR-H1, HVR-H2, and HVR-H3 comprising the amino acid sequences of SEQ ID NO:
- 13, 14, and 15, respectively, and HVR-L1, HVR-L2, and HVR-L3 comprising the amino acid sequences of SEQ ID NO:
- 16, 17, and 18, respectively;
- (c) HVR-H1, HVR-H2, and HVR-H3 comprising the amino acid sequences of SEQ ID NO:
- 19, 20, and 21, respectively, and HVR-L1, HVR-L2, and HVR-L3 comprising the amino acid sequences of SEQ ID NO:
- 22, 23, and 24, respectively;
- or
- (d) HVR-H1, HVR-H2, and HVR-H3 comprising the amino acid sequences of SEQ ID NO:
- 25, 26, and 27, respectively, and HVR-L1, HVR-L2, and HVR-L3 comprising the amino acid sequences of SEQ ID NO:
- 28, 29, and 30, respectively.
A method of treating a subject having a locally advanced, recurrent, or metastatic solid tumor, the method comprising administering to the subject an anti-cancer therapy comprising an anti-latent TGF-beta 1 antibody at a dosage of 1800 mg every three weeks (Q3W), wherein the anti-latent TGF-beta 1 antibody comprises the following six HVRs:
- (a) HVR-H1, HVR-H2, and HVR-H3 comprising the amino acid sequences of SEQ ID NO:
- 1, 2, and 3, respectively, and HVR-L1, HVR-L2, and HVR-L3 comprising the amino acid sequences of SEQ ID NO:
- 4, 5, and 6, respectively;
- (b) HVR-H1, HVR-H2, and HVR-H3 comprising the amino acid sequences of SEQ ID NO:
- 13, 14, and 15, respectively, and HVR-L1, HVR-L2, and HVR-L3 comprising the amino acid sequences of SEQ ID NO:
- 16, 17, and 18, respectively;
- (c) HVR-H1, HVR-H2, and HVR-H3 comprising the amino acid sequences of SEQ ID NO:
- 19, 20, and 21, respectively, and HVR-L1, HVR-L2, and HVR-L3 comprising the amino acid sequences of SEQ ID NO:
- 22, 23, and 24, respectively;
- or
- (d) HVR-H1, HVR-H2, and HVR-H3 comprising the amino acid sequences of SEQ ID NO:
- 25, 26, and 27, respectively, and HVR-L1, HVR-L2, and HVR-L3 comprising the amino acid sequences of SEQ ID NO:
- 28, 29, and 30, respectively.
A method of treating a subject having a locally advanced, recurrent, or metastatic solid tumor, the method comprising administering to the subject an anti-cancer therapy comprising an anti-latent TGF-beta 1 antibody at a dosage of 1200 mg, wherein the anti-latent TGF-beta 1 antibody comprises the following six HVRs:
- (a) HVR-H1, HVR-H2, and HVR-H3 comprising the amino acid sequences of SEQ ID NO:
- 1, 2, and 3, respectively, and HVR-L1, HVR-L2, and HVR-L3 comprising the amino acid sequences of SEQ ID NO:
- 4, 5, and 6, respectively;
- (b) HVR-H1, HVR-H2, and HVR-H3 comprising the amino acid sequences of SEQ ID NO:
- 13, 14, and 15, respectively, and HVR-L1, HVR-L2, and HVR-L3 comprising the amino acid sequences of SEQ ID NO:
- 16, 17, and 18, respectively;
- (c) HVR-H1, HVR-H2, and HVR-H3 comprising the amino acid sequences of SEQ ID NO:
- 19, 20, and 21, respectively, and HVR-L1, HVR-L2, and HVR-L3 comprising the amino acid sequences of SEQ ID NO:
- 22, 23, and 24, respectively;
- or
- (d) HVR-H1, HVR-H2, and HVR-H3 comprising the amino acid sequences of SEQ ID NO:
- 25, 26, and 27, respectively, and HVR-L1, HVR-L2, and HVR-L3 comprising the amino acid sequences of SEQ ID NO:
- 28, 29, and 30, respectively.
A method of treating a subject having a locally advanced, recurrent, or metastatic solid tumor, the method comprising administering to the subject an anti-cancer therapy comprising an anti-latent TGF-beta 1 antibody at a dosage of 1200 mg every two weeks (Q2W), wherein the anti-latent TGF-beta 1 antibody comprises the following six HVRs:
- (a) HVR-H1, HVR-H2, and HVR-H3 comprising the amino acid sequences of SEQ ID NO:
- 1, 2, and 3, respectively, and HVR-L1, HVR-L2, and HVR-L3 comprising the amino acid sequences of SEQ ID NO:
- 4, 5, and 6, respectively;
- (b) HVR-H1, HVR-H2, and HVR-H3 comprising the amino acid sequences of SEQ ID NO:
- 13, 14, and 15, respectively, and HVR-L1, HVR-L2, and HVR-L3 comprising the amino acid sequences of SEQ ID NO:
- 16, 17, and 18, respectively;
- (c) HVR-H1, HVR-H2, and HVR-H3 comprising the amino acid sequences of SEQ ID NO:
- 19, 20, and 21, respectively, and HVR-L1, HVR-L2, and HVR-L3 comprising the amino acid sequences of SEQ ID NO:
- 22, 23, and 24, respectively;
- or
- (d) HVR-H1, HVR-H2, and HVR-H3 comprising the amino acid sequences of SEQ ID NO:
- 25, 26, and 27, respectively, and HVR-L1, HVR-L2, and HVR-L3 comprising the amino acid sequences of SEQ ID NO:
- 28, 29, and 30, respectively.
A method of treating a subject having a locally advanced, recurrent, or metastatic NSCLC, the method comprising administering to the subject an anti-cancer therapy in a dosing regimen comprising one or more 21-day dosing cycles, wherein the anti-cancer therapy comprises:
- (i) an anti-latent TGF-beta 1 antibody at a dosage of 1800 mg intravenously on Day 1 of each 21-day dosing cycle, wherein the anti-latent TGF-beta 1 antibody comprises the following six HVRs:
- (a) HVR-H1, HVR-H2, and HVR-H3 comprising the amino acid sequences of SEQ ID NO:
- 1, 2, and 3, respectively, and HVR-L1, HVR-L2, and HVR-L3 comprising the amino acid sequences of SEQ ID NO:
- 4, 5, and 6, respectively;
- (b) HVR-H1, HVR-H2, and HVR-H3 comprising the amino acid sequences of SEQ ID NO:
- 13, 14, and 15, respectively, and HVR-L1, HVR-L2, and HVR-L3 comprising the amino acid sequences of SEQ ID NO:
- 16, 17, and 18, respectively;
- (c) HVR-H1, HVR-H2, and HVR-H3 comprising the amino acid sequences of SEQ ID NO:
- 19, 20, and 21, respectively, and HVR-L1, HVR-L2, and HVR-L3 comprising the amino acid sequences of SEQ ID NO:
- 22, 23, and 24, respectively;
- or
- (d) HVR-H1, HVR-H2, and HVR-H3 comprising the amino acid sequences of SEQ ID NO:
- 25, 26, and 27, respectively, and HVR-L1, HVR-L2, and HVR-L3 comprising the amino acid sequences of SEQ ID NO:
- 28, 29, and 30, respectively;
- and
- (ii) atezolizumab at a dosage of 1200 mg intravenously on Day 1 of each 21-day dosing cycle.
A method of treating a subject having a locally advanced, recurrent, or metastatic gastric cancer, the method comprising administering to the subject an anti-cancer therapy in a dosing regimen comprising one or more 21-day dosing cycles, wherein the anti-cancer therapy comprises:
- (i) an anti-latent TGF-beta 1 antibody at a dosage of 1800 mg intravenously on Day 1 of each 21-day dosing cycle, wherein the anti-latent TGF-beta 1 antibody comprises the following six HVRs:
- (a) HVR-H1, HVR-H2, and HVR-H3 comprising the amino acid sequences of SEQ ID NO:
- 1, 2, and 3, respectively, and HVR-L1, HVR-L2, and HVR-L3 comprising the amino acid sequences of SEQ ID NO:
- 4, 5, and 6, respectively;
- (b) HVR-H1, HVR-H2, and HVR-H3 comprising the amino acid sequences of SEQ ID NO:
- 13, 14, and 15, respectively, and HVR-L1, HVR-L2, and HVR-L3 comprising the amino acid sequences of SEQ ID NO:
- 16, 17, and 18, respectively;
- (c) HVR-H1, HVR-H2, and HVR-H3 comprising the amino acid sequences of SEQ ID NO:
- 19, 20, and 21, respectively, and HVR-L1, HVR-L2, and HVR-L3 comprising the amino acid sequences of SEQ ID NO:
- 22, 23, and 24, respectively;
- or
- (d) HVR-H1, HVR-H2, and HVR-H3 comprising the amino acid sequences of SEQ ID NO:
- 25, 26, and 27, respectively, and HVR-L1, HVR-L2, and HVR-L3 comprising the amino acid sequences of SEQ ID NO:
- 28, 29, and 30, respectively;
- and
- (ii) nivolumab at a dosage of 360 mg intravenously on Day 1 of each 21-day dosing cycle;
- (iii)
- (a) capecitabine at a dosage of 1000 mg/m2 orally twice daily on Days 1-14 of each 21-day dosing cycle, or
- (b) S-1 at a dosage of 40 mg/m2 orally twice daily on Days 1-14 of each 21-day dosing cycle;
- and
- (iv) oxaliplatin at a dosage of 130 mg/m2 intravenously on Day 1 of each 21-day dosing cycle.
A method of treating a subject having a locally advanced, recurrent, or metastatic PDAC, the method comprising administering to the subject an anti-cancer therapy in a dosing regimen comprising one or more 28-day dosing cycles, wherein the anti-cancer therapy comprises:
- (i) an anti-latent TGF-beta 1 antibody at a dosage of 1200 mg intravenously on Days 1 and 15 of each 28-day dosing cycle, wherein the anti-latent TGF-beta 1 antibody comprises the following six HVRs:
- (a) HVR-H1, HVR-H2, and HVR-H3 comprising the amino acid sequences of SEQ ID NO:
- 1, 2, and 3, respectively, and HVR-L1, HVR-L2, and HVR-L3 comprising the amino acid sequences of SEQ ID NO:
- 4, 5, and 6, respectively;
- (b) HVR-H1, HVR-H2, and HVR-H3 comprising the amino acid sequences of SEQ ID NO:
- 13, 14, and 15, respectively, and HVR-L1, HVR-L2, and HVR-L3 comprising the amino acid sequences of SEQ ID NO:
- 16, 17, and 18, respectively;
- (c) HVR-H1, HVR-H2, and HVR-H3 comprising the amino acid sequences of SEQ ID NO:
- 19, 20, and 21, respectively, and HVR-L1, HVR-L2, and HVR-L3 comprising the amino acid sequences of SEQ ID NO:
- 22, 23, and 24, respectively;
- or
- (d) HVR-H1, HVR-H2, and HVR-H3 comprising the amino acid sequences of SEQ ID NO:
- 25, 26, and 27, respectively, and HVR-L1, HVR-L2, and HVR-L3 comprising the amino acid sequences of SEQ ID NO:
- 28, 29, and 30, respectively;
- (ii) atezolizumab at a dosage of 840 mg intravenously on Days 1 and 15 of each 28-day dosing cycle;
- (iii) nab-paclitaxel at a dose of 125 mg/m2 on Days 1, 8, and 15 of each 28-day dosing cycle;
- and
- (iv) gemcitabine at a dosage of 1000 mg/m2 intravenously on Days 1, 8, and 15 of each 28-day dosing cycle.
A method of treating a subject having a locally advanced, recurrent, or metastatic UC, the method comprising administering to the subject an anti-cancer therapy in a dosing regimen comprising one or more 21-day dosing cycles, wherein the anti-cancer therapy comprises:
- (i) an anti-latent TGF-beta 1 antibody at a dosage of 1800 mg intravenously on Day 1 of each 21-day dosing cycle, wherein the anti-latent TGF-beta 1 antibody comprises the following six HVRs:
- (a) HVR-H1, HVR-H2, and HVR-H3 comprising the amino acid sequences of SEQ ID NO:
- 1, 2, and 3, respectively, and HVR-L1, HVR-L2, and HVR-L3 comprising the amino acid sequences of SEQ ID NO:
- 4, 5, and 6, respectively;
- (b) HVR-H1, HVR-H2, and HVR-H3 comprising the amino acid sequences of SEQ ID NO:
- 13, 14, and 15, respectively, and HVR-L1, HVR-L2, and HVR-L3 comprising the amino acid sequences of SEQ ID NO:
- 16, 17, and 18, respectively;
- (c) HVR-H1, HVR-H2, and HVR-H3 comprising the amino acid sequences of SEQ ID NO:
- 19, 20, and 21, respectively, and HVR-L1, HVR-L2, and HVR-L3 comprising the amino acid sequences of SEQ ID NO:
- 22, 23, and 24, respectively;
- or
- (d) HVR-H1, HVR-H2, and HVR-H3 comprising the amino acid sequences of SEQ ID NO:
- 25, 26, and 27, respectively, and HVR-L1, HVR-L2, and HVR-L3 comprising the amino acid sequences of SEQ ID NO:
- 28, 29, and 30, respectively;
- and
- (ii) atezolizumab at a dosage of 1200 mg intravenously on Day 1 of each 21-day dosing cycle.
A method of treating a subject having a metastatic non-squamous NSCLC or a metastatic squamous NSCLC, the method comprising administering to the subject an anti-cancer therapy in a dosing regimen comprising one or more 21-day dosing cycles, wherein the anti-cancer therapy comprises:
- (i) an anti-latent TGF-beta 1 antibody at a dosage of 1800 mg intravenously on Day 1 of each 21-day dosing cycle, wherein the anti-latent TGF-beta 1 antibody comprises the following six HVRs:
- (a) an HVR-H1 comprising the amino acid sequence of SEAMN (SEQ ID NO:
- 1);
- (b) an HVR-H2 comprising the amino acid sequence of YIYTSGTTYRANWARG (SEQ ID NO:
- 2);
- (c) an HVR-H3 comprising the amino acid sequence of GTGIYDYYYWVMDL (SEQ ID NO:3);
- (d) an HVR-L1 comprising the amino acid sequence of QASQSISTYLA (SEQ ID NO:
- 4);
- (e) an HVR-L2 comprising the amino acid sequence of AASTLES (SEQ ID NO:
- 5);
- and
- (f) an HVR-L3 comprising the amino acid sequence of QSYSDGDSVG (SEQ ID NO:
- 6);
- and
- (ii) atezolizumab at a dosage of 1200 mg intravenously on Day 1 of each 21-day dosing cycle,
- wherein the subject has had disease progression during or following treatment for metastatic or locally advanced, inoperable NSCLC that comprised a platinum-containing chemotherapy regimen and a PD-1 axis binding antagonist, given in combination as one line of therapy or as two separate lines of therapy, in either order, for a maximum of two prior lines of systemic therapy.
A method of treating a subject having a locally advanced, unresectable, or metastatic HER2-negative gastric cancer, the method comprising administering to the subject an anti-cancer therapy in a dosing regimen comprising one or more 21-day dosing cycles, wherein the anti-cancer therapy comprises:
- (i) an anti-latent TGF-beta 1 antibody at a dosage of 1800 mg intravenously on Day 1 of each 21-day dosing cycle, wherein the anti-latent TGF-beta 1 antibody comprises the following six HVRs:
- (a) an HVR-H1 comprising the amino acid sequence of SEAMN (SEQ ID NO:
- 1);
- (b) an HVR-H2 comprising the amino acid sequence of YIYTSGTTYRANWARG (SEQ ID NO:
- 2);
- (c) an HVR-H3 comprising the amino acid sequence of GTGIYDYYYWVMDL (SEQ ID NO:3);
- (d) an HVR-L1 comprising the amino acid sequence of QASQSISTYLA (SEQ ID NO:
- 4);
- (e) an HVR-L2 comprising the amino acid sequence of AASTLES (SEQ ID NO:
- 5);
- and
- (f) an HVR-L3 comprising the amino acid sequence of QSYSDGDSVG (SEQ ID NO:
- 6);
- (ii) nivolumab at a dosage of 360 mg intravenously on Day 1 of each 21-day dosing cycle;
- (iii)
- (a) capecitabine at a dosage of 1000 mg/m2 orally twice daily on Days 1-14 of each 21-day dosing cycle, or
- (b) S-1 at a dosage of 40 mg/m2 orally twice daily on Days 1-14 of each 21-day dosing cycle;
- and
- (iv) oxaliplatin at a dosage of 130 mg/m2 intravenously on Day 1 of each 21-day dosing cycle,
- wherein the subject is previously untreated for the locally advanced, unresectable, or metastatic HER2-negative gastric cancer.
A method of treating a subject having a metastatic PDAC, the method comprising administering to the subject an anti-cancer therapy in a dosing regimen comprising one or more 28-day dosing cycles, wherein the anti-cancer therapy comprises:
- (i) an anti-latent TGF-beta 1 antibody at a dosage of 1200 mg intravenously on Days 1 and 15 of each 28-day dosing cycle, wherein the anti-latent TGF-beta 1 antibody comprises the following six HVRs:
- (a) an HVR-H1 comprising the amino acid sequence of SEAMN (SEQ ID NO:
- 1);
- (b) an HVR-H2 comprising the amino acid sequence of YIYTSGTTYRANWARG (SEQ ID NO:
- 2);
- (c) an HVR-H3 comprising the amino acid sequence of GTGIYDYYYWVMDL (SEQ ID NO:3);
- (d) an HVR-L1 comprising the amino acid sequence of QASQSISTYLA (SEQ ID NO:
- 4);
- (e) an HVR-L2 comprising the amino acid sequence of AASTLES (SEQ ID NO:
- 5);
- and
- (f) an HVR-L3 comprising the amino acid sequence of QSYSDGDSVG (SEQ ID NO:
- 6);
- (ii) atezolizumab at a dosage of 840 mg intravenously on Days 1 and 15 of each 28-day dosing cycle;
- (iii) nab-paclitaxel at a dose of 125 mg/m2 on Days 1, 8, and 15 of each 28-day dosing cycle;
- and
- (iv) gemcitabine at a dosage of 1000 mg/m2 intravenously on Days 1, 8, and 15 of each 28-day dosing cycle,
- wherein the subject is previously untreated for the metastatic PDAC.
A method of treating a subject having a locally advanced or metastatic UC, the method comprising administering to the subject an anti-cancer therapy in a dosing regimen comprising one or more 21-day dosing cycles, wherein the anti-cancer therapy comprises:
- (i) an anti-latent TGF-beta 1 antibody at a dosage of 1800 mg intravenously on Day 1 of each 21-day dosing cycle, wherein the anti-latent TGF-beta 1 antibody comprises the following six HVRs:
- (a) an HVR-H1 comprising the amino acid sequence of SEAMN (SEQ ID NO:
- 1);
- (b) an HVR-H2 comprising the amino acid sequence of YIYTSGTTYRANWARG (SEQ ID NO:
- 2);
- (c) an HVR-H3 comprising the amino acid sequence of GTGIYDYYYWVMDL (SEQ ID NO:3);
- (d) an HVR-L1 comprising the amino acid sequence of QASQSISTYLA (SEQ ID NO:
- 4);
- (e) an HVR-L2 comprising the amino acid sequence of AASTLES (SEQ ID NO:
- 5);
- and
- (f) an HVR-L3 comprising the amino acid sequence of QSYSDGDSVG (SEQ ID NO:
- 6);
- and
- (ii) atezolizumab at a dosage of 1200 mg intravenously on Day 1 of each 21-day dosing cycle, wherein:
- the subject is previously untreated for the locally advanced or metastatic UC and is ineligible for cisplatin-containing chemotherapy;
- or
- the subject has previously received at least one platinum-containing chemotherapy regimen.
An anti-latent TGF-beta 1 for use in treatment of a subject having a locally advanced, recurrent, or metastatic solid tumor, the treatment comprising administering to the subject an anti-cancer therapy comprising an anti-latent TGF-beta 1 antibody at a dosage of 1800 mg, wherein the anti-latent TGF-beta 1 antibody comprises the following six HVRs:
- (a) HVR-H1, HVR-H2, and HVR-H3 comprising the amino acid sequences of SEQ ID NO:
- 1, 2, and 3, respectively, and HVR-L1, HVR-L2, and HVR-L3 comprising the amino acid sequences of SEQ ID NO:
- 4, 5, and 6, respectively;
- (b) HVR-H1, HVR-H2, and HVR-H3 comprising the amino acid sequences of SEQ ID NO:
- 13, 14, and 15, respectively, and HVR-L1, HVR-L2, and HVR-L3 comprising the amino acid sequences of SEQ ID NO:
- 16, 17, and 18, respectively;
- (c) HVR-H1, HVR-H2, and HVR-H3 comprising the amino acid sequences of SEQ ID NO:
- 19, 20, and 21, respectively, and HVR-L1, HVR-L2, and HVR-L3 comprising the amino acid sequences of SEQ ID NO:
- 22, 23, and 24, respectively;
- or
- (d) HVR-H1, HVR-H2, and HVR-H3 comprising the amino acid sequences of SEQ ID NO:
- 25, 26, and 27, respectively, and HVR-L1, HVR-L2, and HVR-L3 comprising the amino acid sequences of SEQ ID NO:
- 28, 29, and 30, respectively.
An anti-latent TGF-beta 1 for use in treatment of a subject having a locally advanced, recurrent, or metastatic solid tumor, the treatment comprising administering to the subject an anti-cancer therapy comprising an anti-latent TGF-beta 1 antibody at a dosage of 1800 mg every three weeks (Q3W), wherein the anti-latent TGF-beta 1 antibody comprises the following six HVRs:
- (a) HVR-H1, HVR-H2, and HVR-H3 comprising the amino acid sequences of SEQ ID NO:
- 1, 2, and 3, respectively, and HVR-L1, HVR-L2, and HVR-L3 comprising the amino acid sequences of SEQ ID NO:
- 4, 5, and 6, respectively;
- (b) HVR-H1, HVR-H2, and HVR-H3 comprising the amino acid sequences of SEQ ID NO:
- 13, 14, and 15, respectively, and HVR-L1, HVR-L2, and HVR-L3 comprising the amino acid sequences of SEQ ID NO:
- 16, 17, and 18, respectively;
- (c) HVR-H1, HVR-H2, and HVR-H3 comprising the amino acid sequences of SEQ ID NO:
- 19, 20, and 21, respectively, and HVR-L1, HVR-L2, and HVR-L3 comprising the amino acid sequences of SEQ ID NO:
- 22, 23, and 24, respectively;
- or
- (d) HVR-H1, HVR-H2, and HVR-H3 comprising the amino acid sequences of SEQ ID NO:
- 25, 26, and 27, respectively, and HVR-L1, HVR-L2, and HVR-L3 comprising the amino acid sequences of SEQ ID NO:
- 28, 29, and 30, respectively.
An anti-latent TGF-beta 1 for use in treatment of a subject having a locally advanced, recurrent, or metastatic solid tumor, the treatment comprising administering to the subject an anti-cancer therapy comprising an anti-latent TGF-beta 1 antibody at a dosage of 1200 mg, wherein the anti-latent TGF-beta 1 antibody comprises the following six HVRs:
- (a) HVR-H1, HVR-H2, and HVR-H3 comprising the amino acid sequences of SEQ ID NO:
- 1, 2, and 3, respectively, and HVR-L1, HVR-L2, and HVR-L3 comprising the amino acid sequences of SEQ ID NO:
- 4, 5, and 6, respectively;
- (b) HVR-H1, HVR-H2, and HVR-H3 comprising the amino acid sequences of SEQ ID NO:
- 13, 14, and 15, respectively, and HVR-L1, HVR-L2, and HVR-L3 comprising the amino acid sequences of SEQ ID NO:
- 16, 17, and 18, respectively;
- (c) HVR-H1, HVR-H2, and HVR-H3 comprising the amino acid sequences of SEQ ID NO:
- 19, 20, and 21, respectively, and HVR-L1, HVR-L2, and HVR-L3 comprising the amino acid sequences of SEQ ID NO:
- 22, 23, and 24, respectively;
- or
- (d) HVR-H1, HVR-H2, and HVR-H3 comprising the amino acid sequences of SEQ ID NO:
- 25, 26, and 27, respectively, and HVR-L1, HVR-L2, and HVR-L3 comprising the amino acid sequences of SEQ ID NO:
- 28, 29, and 30, respectively.
An anti-latent TGF-beta 1 for use in treatment of a subject having a locally advanced, recurrent, or metastatic solid tumor, the treatment comprising administering to the subject an anti-cancer therapy comprising an anti-latent TGF-beta 1 antibody at a dosage of 1200 mg every two weeks (Q2W), wherein the anti-latent TGF-beta 1 antibody comprises the following six HVRs:
- (a) HVR-H1, HVR-H2, and HVR-H3 comprising the amino acid sequences of SEQ ID NO:
- 1, 2, and 3, respectively, and HVR-L1, HVR-L2, and HVR-L3 comprising the amino acid sequences of SEQ ID NO:
- 4, 5, and 6, respectively;
- (b) HVR-H1, HVR-H2, and HVR-H3 comprising the amino acid sequences of SEQ ID NO:
- 13, 14, and 15, respectively, and HVR-L1, HVR-L2, and HVR-L3 comprising the amino acid sequences of SEQ ID NO:
- 16, 17, and 18, respectively;
- (c) HVR-H1, HVR-H2, and HVR-H3 comprising the amino acid sequences of SEQ ID NO:
- 19, 20, and 21, respectively, and HVR-L1, HVR-L2, and HVR-L3 comprising the amino acid sequences of SEQ ID NO:
- 22, 23, and 24, respectively;
- or
- (d) HVR-H1, HVR-H2, and HVR-H3 comprising the amino acid sequences of SEQ ID NO:
- 25, 26, and 27, respectively, and HVR-L1, HVR-L2, and HVR-L3 comprising the amino acid sequences of SEQ ID NO:
- 28, 29, and 30, respectively.
An anti-latent TGF-beta 1 for use in treatment of a subject having a locally advanced, recurrent, or metastatic NSCLC, the treatment comprising administering to the subject an anti-cancer therapy in a dosing regimen comprising one or more 21-day dosing cycles, wherein the anti-cancer therapy comprises:
- (i) an anti-latent TGF-beta 1 antibody at a dosage of 1800 mg intravenously on Day 1 of each 21-day dosing cycle, wherein the anti-latent TGF-beta 1 antibody comprises the following six HVRs:
- (a) HVR-H1, HVR-H2, and HVR-H3 comprising the amino acid sequences of SEQ ID NO:
- 1, 2, and 3, respectively, and HVR-L1, HVR-L2, and HVR-L3 comprising the amino acid sequences of SEQ ID NO:
- 4, 5, and 6, respectively;
- (b) HVR-H1, HVR-H2, and HVR-H3 comprising the amino acid sequences of SEQ ID NO:
- 13, 14, and 15, respectively, and HVR-L1, HVR-L2, and HVR-L3 comprising the amino acid sequences of SEQ ID NO:
- 16, 17, and 18, respectively;
- (c) HVR-H1, HVR-H2, and HVR-H3 comprising the amino acid sequences of SEQ ID NO:
- 19, 20, and 21, respectively, and HVR-L1, HVR-L2, and HVR-L3 comprising the amino acid sequences of SEQ ID NO:
- 22, 23, and 24, respectively;
- or
- (d) HVR-H1, HVR-H2, and HVR-H3 comprising the amino acid sequences of SEQ ID NO:
- 25, 26, and 27, respectively, and HVR-L1, HVR-L2, and HVR-L3 comprising the amino acid sequences of SEQ ID NO:
- 28, 29, and 30, respectively;
- and
- (ii) atezolizumab at a dosage of 1200 mg intravenously on Day 1 of each 21-day dosing cycle.
An anti-latent TGF-beta 1 for use in treatment of a subject having a locally advanced, recurrent, or metastatic gastric cancer, the treatment comprising administering to the subject an anti-cancer therapy in a dosing regimen comprising one or more 21-day dosing cycles, wherein the anti-cancer therapy comprises:
- (i) an anti-latent TGF-beta 1 antibody at a dosage of 1800 mg intravenously on Day 1 of each 21-day dosing cycle, wherein the anti-latent TGF-beta 1 antibody comprises the following six HVRs:
- (a) HVR-H1, HVR-H2, and HVR-H3 comprising the amino acid sequences of SEQ ID NO:
- 1, 2, and 3, respectively, and HVR-L1, HVR-L2, and HVR-L3 comprising the amino acid sequences of SEQ ID NO:
- 4, 5, and 6, respectively;
- (b) HVR-H1, HVR-H2, and HVR-H3 comprising the amino acid sequences of SEQ ID NO:
- 13, 14, and 15, respectively, and HVR-L1, HVR-L2, and HVR-L3 comprising the amino acid sequences of SEQ ID NO:
- 16, 17, and 18, respectively;
- (c) HVR-H1, HVR-H2, and HVR-H3 comprising the amino acid sequences of SEQ ID NO:
- 19, 20, and 21, respectively, and HVR-L1, HVR-L2, and HVR-L3 comprising the amino acid sequences of SEQ ID NO:
- 22, 23, and 24, respectively;
- or
- (d) HVR-H1, HVR-H2, and HVR-H3 comprising the amino acid sequences of SEQ ID NO:
- 25, 26, and 27, respectively, and HVR-L1, HVR-L2, and HVR-L3 comprising the amino acid sequences of SEQ ID NO:
- 28, 29, and 30, respectively;
- (ii) nivolumab at a dosage of 360 mg intravenously on Day 1 of each 21-day dosing cycle;
- (iii)
- (a) capecitabine at a dosage of 1000 mg/m2 orally twice daily on Days 1-14 of each 21-day dosing cycle, or
- (b) S-1 at a dosage of 40 mg/m2 orally twice daily on Days 1-14 of each 21-day dosing cycle;
- and
- (iv) oxaliplatin at a dosage of 130 mg/m2 intravenously on Day 1 of each 21-day dosing cycle.
An anti-latent TGF-beta 1 for use in treatment of a subject having a locally advanced, recurrent, or metastatic PDAC, the treatment comprising administering to the subject an anti-cancer therapy in a dosing regimen comprising one or more 28-day dosing cycles, wherein the anti-cancer therapy comprises:
- (i) an anti-latent TGF-beta 1 antibody at a dosage of 1200 mg intravenously on Days 1 and 15 of each 28-day dosing cycle, wherein the anti-latent TGF-beta 1 antibody comprises the following six HVRs:
- (a) HVR-H1, HVR-H2, and HVR-H3 comprising the amino acid sequences of SEQ ID NO:
- 1, 2, and 3, respectively, and HVR-L1, HVR-L2, and HVR-L3 comprising the amino acid sequences of SEQ ID NO:
- 4, 5, and 6, respectively;
- (b) HVR-H1, HVR-H2, and HVR-H3 comprising the amino acid sequences of SEQ ID NO:
- 13, 14, and 15, respectively, and HVR-L1, HVR-L2, and HVR-L3 comprising the amino acid sequences of SEQ ID NO:
- 16, 17, and 18, respectively;
- (c) HVR-H1, HVR-H2, and HVR-H3 comprising the amino acid sequences of SEQ ID NO:
- 19, 20, and 21, respectively, and HVR-L1, HVR-L2, and HVR-L3 comprising the amino acid sequences of SEQ ID NO:
- 22, 23, and 24, respectively;
- or
- (d) HVR-H1, HVR-H2, and HVR-H3 comprising the amino acid sequences of SEQ ID NO:
- 25, 26, and 27, respectively, and HVR-L1, HVR-L2, and HVR-L3 comprising the amino acid sequences of SEQ ID NO:
- 28, 29, and 30, respectively;
- (ii) atezolizumab at a dosage of 840 mg intravenously on Days 1 and 15 of each 28-day dosing cycle;
- (iii) nab-paclitaxel at a dose of 125 mg/m2 on Days 1, 8, and 15 of each 28-day dosing cycle;
- and
- (iv) gemcitabine at a dosage of 1000 mg/m2 intravenously on Days 1, 8, and 15 of each 28-day dosing cycle.
An anti-latent TGF-beta 1 for use in treatment of a subject having a locally advanced, recurrent, or metastatic UC, the treatment comprising administering to the subject an anti-cancer therapy in a dosing regimen comprising one or more 21-day dosing cycles, wherein the anti-cancer therapy comprises:
- (i) an anti-latent TGF-beta 1 antibody at a dosage of 1800 mg intravenously on Day 1 of each 21-day dosing cycle, wherein the anti-latent TGF-beta 1 antibody comprises the following six HVRs:
- (a) HVR-H1, HVR-H2, and HVR-H3 comprising the amino acid sequences of SEQ ID NO:
- 1, 2, and 3, respectively, and HVR-L1, HVR-L2, and HVR-L3 comprising the amino acid sequences of SEQ ID NO:
- 4, 5, and 6, respectively;
- (b) HVR-H1, HVR-H2, and HVR-H3 comprising the amino acid sequences of SEQ ID NO:
- 13, 14, and 15, respectively, and HVR-L1, HVR-L2, and HVR-L3 comprising the amino acid sequences of SEQ ID NO:
- 16, 17, and 18, respectively;
- (c) HVR-H1, HVR-H2, and HVR-H3 comprising the amino acid sequences of SEQ ID NO:
- 19, 20, and 21, respectively, and HVR-L1, HVR-L2, and HVR-L3 comprising the amino acid sequences of SEQ ID NO:
- 22, 23, and 24, respectively;
- or
- (d) HVR-H1, HVR-H2, and HVR-H3 comprising the amino acid sequences of SEQ ID NO:
- 25, 26, and 27, respectively, and HVR-L1, HVR-L2, and HVR-L3 comprising the amino acid sequences of SEQ ID NO:
- 28, 29, and 30, respectively;
- and
- (ii) atezolizumab at a dosage of 1200 mg intravenously on Day 1 of each 21-day dosing cycle.
An anti-latent TGF-beta 1 for use in treatment of a subject having a metastatic non-squamous NSCLC or a metastatic squamous NSCLC, the treatment comprising administering to the subject an anti-cancer therapy in a dosing regimen comprising one or more 21-day dosing cycles, wherein the anti-cancer therapy comprises:
- (i) an anti-latent TGF-beta 1 antibody at a dosage of 1800 mg intravenously on Day 1 of each 21-day dosing cycle, wherein the anti-latent TGF-beta 1 antibody comprises the following six HVRs:
- (a) an HVR-H1 comprising the amino acid sequence of SEAMN (SEQ ID NO:
- 1);
- (b) an HVR-H2 comprising the amino acid sequence of YIYTSGTTYRANWARG (SEQ ID NO:
- 2);
- (c) an HVR-H3 comprising the amino acid sequence of GTGIYDYYYWVMDL (SEQ ID NO:3);
- (d) an HVR-L1 comprising the amino acid sequence of QASQSISTYLA (SEQ ID NO:
- 4);
- (e) an HVR-L2 comprising the amino acid sequence of AASTLES (SEQ ID NO:
- 5);
- and
- (f) an HVR-L3 comprising the amino acid sequence of QSYSDGDSVG (SEQ ID NO:
- 6);
- and
- (ii) atezolizumab at a dosage of 1200 mg intravenously on Day 1 of each 21-day dosing cycle,
- wherein the subject has had disease progression during or following treatment for metastatic or locally advanced, inoperable NSCLC that comprised a platinum-containing chemotherapy regimen and a PD-1 axis binding antagonist, given in combination as one line of therapy or as two separate lines of therapy, in either order, for a maximum of two prior lines of systemic therapy.
An anti-latent TGF-beta 1 for use in treatment of a subject having a locally advanced, unresectable, or metastatic HER2-negative gastric cancer, the treatment comprising administering to the subject an anti-cancer therapy in a dosing regimen comprising one or more 21-day dosing cycles, wherein the anti-cancer therapy comprises:
- (i) an anti-latent TGF-beta 1 antibody at a dosage of 1800 mg intravenously on Day 1 of each 21-day dosing cycle, wherein the anti-latent TGF-beta 1 antibody comprises the following six HVRs:
- (a) an HVR-H1 comprising the amino acid sequence of SEAMN (SEQ ID NO:
- 1);
- (b) an HVR-H2 comprising the amino acid sequence of YIYTSGTTYRANWARG (SEQ ID NO:
- 2);
- (c) an HVR-H3 comprising the amino acid sequence of GTGIYDYYYWVMDL (SEQ ID NO:3);
- (d) an HVR-L1 comprising the amino acid sequence of QASQSISTYLA (SEQ ID NO:
- 4);
- (e) an HVR-L2 comprising the amino acid sequence of AASTLES (SEQ ID NO:
- 5);
- and
- (f) an HVR-L3 comprising the amino acid sequence of QSYSDGDSVG (SEQ ID NO:
- 6);
- (ii) nivolumab at a dosage of 360 mg intravenously on Day 1 of each 21-day dosing cycle;
- (iii)
- (a) capecitabine at a dosage of 1000 mg/m2 orally twice daily on Days 1-14 of each 21-day dosing cycle, or
- (b) S-1 at a dosage of 40 mg/m2 orally twice daily on Days 1-14 of each 21-day dosing cycle;
- and
- (iv) oxaliplatin at a dosage of 130 mg/m2 intravenously on Day 1 of each 21-day dosing cycle,
- wherein the subject is previously untreated for the locally advanced, unresectable, or metastatic HER2-negative gastric cancer.
An anti-latent TGF-beta 1 for use in treatment of a subject having a metastatic PDAC, the treatment comprising administering to the subject an anti-cancer therapy in a dosing regimen comprising one or more 28-day dosing cycles, wherein the anti-cancer therapy comprises:
- (i) an anti-latent TGF-beta 1 antibody at a dosage of 1200 mg intravenously on Days 1 and 15 of each 28-day dosing cycle, wherein the anti-latent TGF-beta 1 antibody comprises the following six HVRs:
- (a) an HVR-H1 comprising the amino acid sequence of SEAMN (SEQ ID NO:
- 1);
- (b) an HVR-H2 comprising the amino acid sequence of YIYTSGTTYRANWARG (SEQ ID NO:
- 2);
- (c) an HVR-H3 comprising the amino acid sequence of GTGIYDYYYWVMDL (SEQ ID NO:3);
- (d) an HVR-L1 comprising the amino acid sequence of QASQSISTYLA (SEQ ID NO:
- 4);
- (e) an HVR-L2 comprising the amino acid sequence of AASTLES (SEQ ID NO:
- 5);
- and
- (f) an HVR-L3 comprising the amino acid sequence of QSYSDGDSVG (SEQ ID NO:
- 6);
- (ii) atezolizumab at a dosage of 840 mg intravenously on Days 1 and 15 of each 28-day dosing cycle;
- (iii) nab-paclitaxel at a dose of 125 mg/m2 on Days 1, 8, and 15 of each 28-day dosing cycle;
- and
- (iv) gemcitabine at a dosage of 1000 mg/m2 intravenously on Days 1, 8, and 15 of each 28-day dosing cycle,
- wherein the subject is previously untreated for the metastatic PDAC.
An anti-latent TGF-beta 1 for use in treatment of a subject having a locally advanced or metastatic UC, the treatment comprising administering to the subject an anti-cancer therapy in a dosing regimen comprising one or more 21-day dosing cycles, wherein the anti-cancer therapy comprises:
- (i) an anti-latent TGF-beta 1 antibody at a dosage of 1800 mg intravenously on Day 1 of each 21-day dosing cycle, wherein the anti-latent TGF-beta 1 antibody comprises the following six HVRs:
- (a) an HVR-H1 comprising the amino acid sequence of SEAMN (SEQ ID NO:
- 1);
- (b) an HVR-H2 comprising the amino acid sequence of YIYTSGTTYRANWARG (SEQ ID NO:
- 2);
- (c) an HVR-H3 comprising the amino acid sequence of GTGIYDYYYWVMDL (SEQ ID NO:3);
- (d) an HVR-L1 comprising the amino acid sequence of QASQSISTYLA (SEQ ID NO:
- 4);
- (e) an HVR-L2 comprising the amino acid sequence of AASTLES (SEQ ID NO:
- 5);
- and
- (f) an HVR-L3 comprising the amino acid sequence of QSYSDGDSVG (SEQ ID NO:
- 6);
- and
- (ii) atezolizumab at a dosage of 1200 mg intravenously on Day 1 of each 21-day dosing cycle, wherein:
- the subject is previously untreated for the locally advanced or metastatic UC and is ineligible for cisplatin-containing chemotherapy;
- or
- the subject has previously received at least one platinum-containing chemotherapy regimen.
A method of treating cancer in a subject having a locally advanced or recurrent tumor, the method comprising administering to the subject an anti-cancer therapy in a dosing regimen comprising one or more 21-day dosing cycles, wherein the anti-cancer therapy comprises:
- (i) an anti-latent TGF-beta 1 antibody at a dosage of 1200 mg to 1800 mg intravenously on Day 1 of each 21-day dosing cycle, wherein the anti-latent TGF-beta 1 antibody comprises the following six HVRs:
- (a) HVR-H1, HVR-H2, and HVR-H3 comprising the amino acid sequences of SEQ ID NO:
- 1, 2, and 3, respectively, and HVR-L1, HVR-L2, and HVR-L3 comprising the amino acid sequences of SEQ ID NO:
- 4, 5, and 6, respectively;
- (b) HVR-H1, HVR-H2, and HVR-H3 comprising the amino acid sequences of SEQ ID NO:
- 13, 14, and 15, respectively, and HVR-L1, HVR-L2, and HVR-L3 comprising the amino acid sequences of SEQ ID NO:
- 16, 17, and 18, respectively;
- (c) HVR-H1, HVR-H2, and HVR-H3 comprising the amino acid sequences of SEQ ID NO:
- 19, 20, and 21, respectively, and HVR-L1, HVR-L2, and HVR-L3 comprising the amino acid sequences of SEQ ID NO:
- 22, 23, and 24, respectively;
- or
- (d) HVR-H1, HVR-H2, and HVR-H3 comprising the amino acid sequences of SEQ ID NO:
- 25, 26, and 27, respectively, and HVR-L1, HVR-L2, and HVR-L3 comprising the amino acid sequences of SEQ ID NO:
- 28, 29, and 30, respectively, and
- (ii) atezolizumab at a dosage of 1200 mg intravenously on Day 1 of each 21-day dosing cycle.
An anti-latent TGF-beta 1 for use in a treatment of cancer in a subject having a locally advanced or recurrent tumor, the treatment comprising administering to the subject an anti-cancer therapy in a dosing regimen comprising one or more 21-day dosing cycles, wherein the anti-cancer therapy comprises:
- (i) an anti-latent TGF-beta 1 antibody at a dosage of 1200 mg to 1800 mg intravenously on Day 1 of each 21-day dosing cycle, wherein the anti-latent TGF-beta 1 antibody comprises the following six HVRs:
- (a) HVR-H1, HVR-H2, and HVR-H3 comprising the amino acid sequences of SEQ ID NO:
- 1, 2, and 3, respectively, and HVR-L1, HVR-L2, and HVR-L3 comprising the amino acid sequences of SEQ ID NO:
- 4, 5, and 6, respectively;
- (b) HVR-H1, HVR-H2, and HVR-H3 comprising the amino acid sequences of SEQ ID NO:
- 13, 14, and 15, respectively, and HVR-L1, HVR-L2, and HVR-L3 comprising the amino acid sequences of SEQ ID NO:
- 16, 17, and 18, respectively;
- (c) HVR-H1, HVR-H2, and HVR-H3 comprising the amino acid sequences of SEQ ID NO:
- 19, 20, and 21, respectively, and HVR-L1, HVR-L2, and HVR-L3 comprising the amino acid sequences of SEQ ID NO:
- 22, 23, and 24, respectively;
- or
- (d) HVR-H1, HVR-H2, and HVR-H3 comprising the amino acid sequences of SEQ ID NO:
- 25, 26, and 27, respectively, and HVR-L1, HVR-L2, and HVR-L3 comprising the amino acid sequences of SEQ ID NO:
- 28, 29, and 30, respectively, and
- (ii) atezolizumab at a dosage of 1200 mg intravenously on Day 1 of each 21-day dosing cycle.
Dependencies are inferred from the claim text.