Methods of treating cancer using anti-ox40 antibodies and pd-1 axis binding antagonists
AssigneeGenentech, Inc.
InventorsIna P. RHEE, Jeong KIM, Mahrukh HUSENI, Eric STEFANICH, Sid SUKUMARAN, Chi-Chung LI
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Abstract
The invention provides methods of treating or delaying progression of cancer in an individual comprising administering to the individual an anti-human OX40 agonist antibody and an anti-PDL1 antibody. In some embodiments, the anti-human OX40 agonist antibody is administered in a dose selected from about 0.8 mg, about 3.2 mg, about 12 mg, about 40 mg, about 80 mg, about 130 mg, about 160 mg, about 300 mg, about 320 mg, about 400 mg, about 600 mg, and about 1200 mg, and the anti-PDL1 antibody is administered at a dose of about 800 mg or about 1200 mg.
Claims81
A method of treating or delaying progression of cancer in an individual comprising administering to the individual:
- (i) an anti-human OX40 agonist antibody at a dose selected from the group consisting of about 0.8 mg, about 3.2 mg, about 12 mg, about 40 mg, about 80 mg, about 130 mg, about 160 mg, about 300 mg, about 320 mg, about 400 mg, about 600 mg, and about 1200 mg, wherein the anti-human OX40 agonist antibody comprises (a) HVR-H1 comprising the amino acid sequence of SEQ ID NO:2;
- (b) HVR-H2 comprising the amino acid sequence of SEQ ID NO:3;
- (c) HVR-H3 comprising the amino acid sequence of SEQ ID NO:4;
- (d) HVR-L1 comprising the amino acid sequence of SEQ ID NO:5;
- (e) HVR-L2 comprising the amino acid sequence of SEQ ID NO:6;
- and (f) HVR-L3 comprising an amino acid sequence selected from SEQ ID NO:7;
- and
- (ii) an anti-PDL1 antibody at a dose of about 800 mg or about 1200 mg, wherein the anti-PDL1 antibody comprises (a) HVR-H1 comprising the amino acid sequence of SEQ ID NO:196;
- (b) HVR-H2 comprising the amino acid sequence of SEQ ID NO:197;
- (c) HVR-H3 comprising the amino acid sequence of SEQ ID NO:198;
- (d) HVR-L1 comprising the amino acid sequence of SEQ ID NO:199;
- (e) HVR-L2 comprising the amino acid sequence of SEQ ID NO:200;
- and (f) HVR-L3 comprising an amino acid sequence selected from SEQ ID NO:201;
- wherein the individual is a human.
A method for determining whether a cancer patient responds to a treatment with an anti-human OX40 agonist antibody and an anti-PDL1 antibody, comprising measuring an expression level of one or more marker genes in a sample obtained from the cancer of the individual, wherein the one or more marker genes are selected from the group consisting of CCR5, CD274, IL-7, TNFRSF14, TGFB1, CD40, CD4, PRF1, TNFSF4, CD86, CXCL9, CD3E, LAG3, PDCD1, CCL28, GZMB, IFNg, and IL-2RA, wherein the expression level of the one or more marker genes is compared with a reference, and wherein an increased expression level of the one or more marker genes as compared with the reference indicates that the cancer patient responds to said treatment.
A method for determining whether a cancer patient responds to a treatment with an anti-human OX40 agonist antibody and an anti-PDL1 antibody, comprising measuring an expression level of one or more marker genes in a sample obtained from the cancer of the individual, wherein the one or more marker genes are selected from the group consisting of CD8b, EOMES, GZMA, GZMB, IFNg, and PRF1, wherein the expression level of the one or more marker genes is compared with a reference, and wherein an increased expression level of the one or more marker genes as compared with the reference indicates that the cancer patient responds to said treatment.
A method for determining whether a cancer patient responds to a treatment with an anti-human OX40 agonist antibody and an anti-PDL1 antibody, comprising measuring an expression level of one or more marker genes in a sample obtained from the cancer of the individual, wherein the one or more marker genes are selected from the group consisting of CCL22, IL-2, RORC, IL-8, CTLA4, and FOXP3, wherein the expression level of the one or more marker genes is compared with a reference, and wherein a decreased expression level of the one or more marker genes as compared with the reference indicates that the cancer patient responds to said treatment.
A kit for treating or delaying progression of cancer in an individual, comprising:
- (i) a container comprising an anti-human OX40 agonist antibody for administration at a dose selected from the group consisting of about 0.8 mg, about 3.2 mg, about 12 mg, about 40 mg, about 80 mg, about 130 mg, about 160 mg, about 300 mg, about 320 mg, about 400 mg, about 600 mg, and about 1200 mg, wherein the anti-human OX40 agonist antibody comprises:
- an HVR-H1 comprising the amino acid sequence of SEQ ID NO:2;
- an HVR-H2 comprising the amino acid sequence of SEQ ID NO:3;
- an HVR-H3 comprising the amino acid sequence of SEQ ID NO:4;
- an HVR-L1 comprising the amino acid sequence of SEQ ID NO:5;
- an HVR-L2 comprising the amino acid sequence of SEQ ID NO:6;
- and an HVR-L3 comprising an amino acid sequence selected from SEQ ID NO:7;
- (ii) a container comprising an anti-PDL1 antibody for administration at a dose of about 800 mg or about 1200 mg, wherein the anti-PDL1 antibody comprises (a) HVR-H1 comprising the amino acid sequence of SEQ ID NO:196;
- (b) HVR-H2 comprising the amino acid sequence of SEQ ID NO:197;
- (c) HVR-H3 comprising the amino acid sequence of SEQ ID NO:198;
- (d) HVR-L1 comprising the amino acid sequence of SEQ ID NO:199;
- (e) HVR-L2 comprising the amino acid sequence of SEQ ID NO:200;
- and (f) HVR-L3 comprising an amino acid sequence selected from SEQ ID NO:201;
- and
- (iii) a package insert with instructions for treating or delaying progression of cancer in an individual, wherein the individual is a human.
Dependencies are inferred from the claim text.