Therapeutic and diagnostic methods for cancer

Patent metadata

Field	Value
Publication number	US-11279767-B2
Application number	US-201816115343-A
Country	US
Kind code	B2
Filing date	Aug 28, 2018
Priority date	Feb 29, 2016
Publication date	Mar 22, 2022
Grant date	Mar 22, 2022

Abstract

The present invention provides therapeutic and diagnostic methods and compositions for cancer, for example, bladder cancer. The invention provides methods of treating bladder cancer, methods of determining whether a patient suffering from bladder cancer is likely to respond to treatment comprising a PD-L1 axis binding antagonist, methods of predicting responsiveness of a patient suffering from bladder cancer to treatment comprising a PD-L1 axis binding antagonist, and methods of selecting a therapy for a patient suffering from bladder cancer, based on somatic mutation levels of genes of the invention (e.g., somatic mutation levels in a tumor sample obtained from the patient).

First claim

What is claimed is:

1. A method of treating a patient suffering from a urothelial bladder cancer, the method comprising administering to the patient a therapeutically effective amount of atezolizumab, wherein a tumor sample obtained from the patient has been determined to have an increased level of mutation load relative to a reference level of mutation load, and wherein the mutation load of the tumor sample reflects the level of somatic mutations in at least one-third of the genes set forth in Table 1.

2. The method of claim 1 , wherein the mutation load of the tumor sample reflects the level of somatic mutations in at least one-half, two-thirds, three-fourths, or all of the genes set forth in Table 1.

3. The method of claim 1 , wherein:
(i) the somatic mutations are substitutions, deletions, and/or insertions; or
(ii) the somatic mutations of the at least one gene set forth in Table 1 are protein-altering somatic mutations; or
(iii) the substitutions, deletions, and/or insertions of (i) are in coding regions.

4. The method of claim 1 , wherein the tumor sample obtained from the patient has a whole-genome mutation load that is higher than a reference level whole-genome mutation load.

5. The method of claim 4 , wherein the reference level whole-genome mutation load is at least about 10 mutations per megabase (Mb).

6. The method of claim 1 , further comprising administering to the patient an effective amount of a second therapeutic agent.

7. The method of claim 6 , wherein the second therapeutic agent is selected from the group consisting of a cytotoxic agent, a growth-inhibitory agent, a radiation therapy agent, an anti-angiogenic agent, and combinations thereof.

8. The method of claim 1 , wherein the urothelial bladder cancer is a locally advanced urothelial bladder cancer or a metastatic urothelial bladder cancer.

9. The method of claim 1 , wherein the patient is ineligible for treatment with a platinum-based chemotherapeutic agent and has not received prior treatment for locally advanced or metastatic urothelial bladder cancer.

10. The method of claim 1 , wherein the tumor sample is a formalin-fixed and paraffin-embedded (FFPE) tumor sample, an archival tumor sample, a fresh tumor sample, or a frozen tumor sample.

11. A method of treating a patient suffering from a locally advanced or metastatic urothelial carcinoma, the method comprising administering to the patient 1200 mg of atezolizumab intravenously on Day 1 of each 21-day cycle, wherein the patient is ineligible for treatment with a platinum-based chemotherapeutic agent and has not received prior treatment for locally advanced or metastatic urothelial carcinoma, wherein a tumor sample obtained from the patient has been determined to have an increased level of mutation load relative to a reference level of mutation load, and wherein the mutation load of the tumor sample reflects the level of somatic mutations in at least one-third of the genes set forth in Table 1.

Assignees

• Genentech Inc
• Found Medicine Inc

Inventors

• Bourgon Richard
• Fabrizio David
• Fine Gregg
• Frampton Garrett M
• Hegde Priti
• Mariathasan Sanjeev
• Stephens Philip J
• Sun James Xin
• Yelensky Roman

Classifications

• Y02A90/10

  Information and communication technologies [ICT] supporting adaptation to climate change, e.g. for weather forecasting or climate simulation · CPC title

• G16H50/30

  for calculating health indices; for individual health risk assessment · CPC title

• G16H20/10

  relating to drugs or medications, e.g. for ensuring correct administration to patients · CPC title

• C12Q2600/156

  Polymorphic or mutational markers · CPC title

• C12Q2600/106

  Pharmacogenomics, i.e. genetic variability in individual responses to drugs and drug metabolism · CPC title