Checkpoint blockade and microsatellite instability

Patent metadata

Field	Value
Publication number	US-11629187-B2
Application number	US-202117354656-A
Country	US
Kind code	B2
Filing date	Jun 22, 2021
Priority date	Nov 13, 2014
Publication date	Apr 18, 2023
Grant date	Apr 18, 2023

Abstract

Blockade of immune checkpoints such as cytotoxic T-lymphocyte antigen-4 (CTLA-4) and programmed death-1 (PD-1) shows promise in patients with cancer. Inhibitory antibodies directed at these receptors have been shown to break immune tolerance and promote anti-tumor immunity. These agents work particularly well in patients with a certain category of tumor. Such tumors may be particularly susceptible to treatment because of the multitude of neoantigens which they produce.

First claim

We claim:

1. A method for treating a patient having a solid tumor selected from the group consisting of: endometrial cancer, small bowel cancer, gastric cancer, ampullary cancer, cholangiocarcinoma, pancreatic cancer, prostate cancer, breast cancer, esophageal cancer, liver cancer, ovarian cancer, uterine cancer, cervical cancer, bladder cancer, testicular cancer and oral cancer, the method comprising:
in response to determining that the solid tumor is microsatellite instability high or DNA mismatch repair deficient, treating a patient having a solid tumor selected from the group consisting of: endometrial cancer, small bowel cancer, gastric cancer, ampullary cancer, cholangiocarcinoma, pancreatic cancer, prostate cancer, breast cancer, esophageal cancer, liver cancer, ovarian cancer, uterine cancer, cervical cancer, bladder cancer, testicular cancer and oral cancer with a therapeutically effective amount of pembrolizumab based on a determination that the solid tumor has progressed following at least one prior cancer treatment, and further based on previous testing of a biological sample obtained from the patient that the patient's solid tumor exhibits at least one marker for high microsatellite instability or DNA mismatch repair deficiency.

2. The method of claim 1 , wherein the biological sample is tumor tissue from the patient.

3. The method of claim 1 , wherein the biological sample is a body fluid from the patient.

4. The method of claim 1 , wherein the solid tumor is microsatellite instability high.

5. The method of claim 1 , wherein the solid tumor is DNA mismatch repair deficient.

6. The method of claim 1 , wherein the solid tumor is metastatic.

7. The method of claim 1 , wherein the pembrolizumab is administered to the patient intravenously.

8. The method of claim 1 , wherein the at least one marker comprises BAT-25, BAT-26, MONO-27, NR-21 or NR-24.

9. The method of claim 1 , wherein the solid tumor is endometrial cancer, small bowel cancer, gastric cancer, ampullary cancer or cholangiocarcinoma.

10. The method of claim 1 , wherein the solid tumor is pancreatic cancer, prostate cancer, breast cancer, esophageal cancer, liver cancer, ovarian cancer, uterine cancer, cervical cancer, bladder cancer, testicular cancer or oral cancer.

11. A method for reducing the risk ofprogression of a solid tumor selected from the group consisting of: endometrial cancer, small bowel cancer, gastric cancer, ampullary cancer, cholangiocarcinoma, pancreatic cancer, prostate cancer, breast cancer, esophageal cancer, liver cancer, ovarian cancer, uterine cancer, cervical cancer, bladder cancer, testicular cancer and oral cancer that has progressed following at least one prior treatment in a patient, the method comprising:
in response to determining that the solid tumor is microsatellite instability high or DNA mismatch repair deficient, treating the patient with a therapeutically effective amount of pembrolizumab based on previous testing of a biological sample obtained from the patient that the patient's solid tumor exhibits at least one marker for high microsatellite instability or DNA mismatch repair deficiency.

12. The method of claim 11 , wherein the biological sample was tumor tissue from the patient.

13. The method of claim 11 , wherein the biological sample was a body fluid from the patient.

14. The method of claim 11 , wherein the solid tumor is microsatellite instability high.

15. The method of claim 11 , wherein the solid tumor is DNA mismatch repair deficient.

16. The method of claim 11 , wherein the solid tumor is metastatic.

17. The method of claim 11 , wherein the pembrolizumab is administered to the patient intravenously.

18. The method of claim 11 , wherein the previous testing comprised assessing one or more of BAT-25, BAT-26, MONO-27, NR-21 and NR-24.

19. The method of claim 11 , wherein the solid tumor is endometrial cancer, small bowel cancer, gastric cancer, ampullary cancer or cholangiocarcinoma.

20. The method of claim 11 , wherein the solid tumor is pancreatic cancer, prostate cancer, breast cancer, esophageal cancer, liver cancer, ovarian cancer, uterine cancer, cervical cancer, bladder cancer, testicular cancer or oral cancer.

21. The method of claim 1 , wherein the solid tumor is endometrial cancer.

22. The method of claim 21 , wherein the endometrial cancer is microsatellite instability high.

23. The method of claim 21 , wherein the endometrial cancer is DNA mismatch repair deficient.

24. The method of claim 21 , wherein the solid tumor is metastatic endometrial cancer.

25. The method of claim 11 , wherein the solid tumor is endometrial cancer.

26. The method of claim 25 , wherein the endometrial cancer is microsatellite instability high.

27. The method of claim 25 , wherein the endometrial cancer is DNA mismatch repair deficient.

28. The method of claim 25 , wherein the solid tumor is metastatic endometrial cancer.

Assignees

• Univ Johns Hopkins

Inventors

• Diaz Luis
• Vogelstein Bert
• Kinzler Kenneth W
• Papadopoulos Nickolas
• Le Dung
• Pardoll Drew M
• Topalian Suzanne L

Classifications

• C12Y113/11052

  Indoleamine 2,3-dioxygenase (1.13.11.52), i.e. indoleamine 2,3-dioxygenase 1 · CPC title

• C07K16/40

  against enzymes · CPC title

• C07K16/30

  from tumour cells · CPC title

• C07K2317/24

  containing regions, domains or residues from different species, e.g. chimeric, humanized or veneered · CPC title

• C12Q2600/156

  Polymorphic or mutational markers · CPC title