Checkpoint blockade and microsatellite instability

Patent metadata

Field	Value
Publication number	US-11325974-B2
Application number	US-202017131326-A
Country	US
Kind code	B2
Filing date	Dec 22, 2020
Priority date	Nov 13, 2014
Publication date	May 10, 2022
Grant date	May 10, 2022

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 cancer in a patient in need thereof,
wherein a tumor sample obtained from the patient has been determined to exhibit an instability of one or more microsatellite markers or a deficiency of one or more mismatch repair markers, the patient having received a prior cancer therapy drug to treat the tumor, the method comprising:
administering an effective amount of pembrolizumab to the patient;
wherein the patient exhibits an outcome that is improved as compared to a corresponding outcome that would be observed in a reference patient that has been administered pembrolizumab, wherein the reference patient has a tumor that does not exhibit an instability of the one or more microsatellite markers or a deficiency of the one or more mismatch repair markers.

2. The method of claim 1 , wherein the cancer in the patient has progressed after the patient received the prior cancer therapy drug.

3. The method of claim 1 , wherein the outcome that is improved is an improved objective response rate (ORR), an improved progression-free survival (PFS), or an improved overall survival (OS).

4. The method of claim 1 , wherein the tumor sample from the patient exhibits an instability of one or more microsatellite markers, wherein the microsatellite marker is BAT-25, BAT-26, MONO-27, NR-21 or NR-24, or
wherein the tumor sample from the patient exhibits a deficiency of one or more mismatch repair markers, wherein the mismatch repair marker is POLE, POLD1, or MYH.

5. The method of claim 1 , wherein the cancer is a metastatic cancer.

6. The method of claim 1 , wherein the cancer is a metastatic colorectal cancer.

7. The method of claim 1 , wherein pembrolizumab is administered by intravenous infusion.

Assignees

• Univ Johns Hopkins

Inventors

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

Classifications

• 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

• C12Q1/6886

  for cancer (immunoassay for cancer G01N33/575) · CPC title

• C07K2317/76

  Antagonist effect on antigen, e.g. neutralization or inhibition of binding · CPC title

• C07K2317/24

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