Microsatellite Instability as a Pharmacogenomic Marker of Therapeutic Response to Immune Checkpoint Inhibition

Case ID:
C13241
Disclosure Date:
9/10/2014

TITLE

Microsatellite Instability as a Pharmacogenomic Marker of Therapeutic Response to Immune Checkpoint Inhibition              

 

CASE NUMBER

C13241

 

UNMET NEED

The programmed death 1 (PD-1) pathway is a negative feedback system that represses Th1 cytotoxic immune responses and that, if unregulated, can damage the host. It is up-regulated in many tumors and in their surrounding microenvironment. Blockade of this pathway with antibodies to PD-1 or its ligands has led to remarkable clinical responses in patients with many different types of cancer, including melanomas, non–small-cell lung cancer, renal-cell carcinoma, bladder cancer, and Hodgkin’s lymphoma. The expression of PD-1 ligands (PD-L1 or PD-L2) on the surface of tumor cells or immune cells is an important — but not a definitive — predictive biomarker of response to PD-1 blockade.     

       

DISEASE INDICATION

Cancers

  

TECHNICAL DESCRIPTION

This trial was conducted using a parallel two-stage design to simultaneously evaluate the efficacy of MK-3475 and MSI as a treatment selection marker for anti-PD-1 therapy. It consisted of two-stage phase 2 studies in parallel in three cohorts of patients. These include, patients with MSI positive colon cancer, patients with MSI negative colon cancer and patients with other MSI positive cancers. The study agent, MK-3475, was administered at 10 mg/kg intravenously every 14 days. The co-primary end points were the immune-related objective response rate and the 20-week immune-related progression-free survival rate.

 

MAJOR RESULTS

1.       This study showed that mismatch-repair status predicted clinical benefit of immune checkpoint blockade with pembrolizumab.

2.       Changes in serum levels of protein biomarkers, such as CEA, corresponded with clinical benefit after a single dose of therapy.

3.       The evaluation of tumor genomes can help guide immunotherapy.

4.       Identification of an approach for the treatment of a specific class of tumors based solely on genetic status.

       

       

ASSOCIATED PUBLICATIONS

- N Engl J Med. 2015 Jun 25;372(26):2509-20 -

 

       

TECHNOLOGY CLASSIFICATION

Primary Category: Clinical Diagnostics

Primary Subcategory: Immunotherapy

 

ASSOCIATED REPORTS OF INVENTION (ROIs) AND INTELLECTUAL PROPERTY (IP) FILING NUMBERS

ROI #                               TITLE                                                        STATUS       PRIORITY DATE        IP FILING NUMBERS

C13241    CHECKPOINT BLOCKADE AND MICROSATELLITE INSTABILITY       PCT Pending       11/13/2014                   US 62/190,977, PCT/US2015/060331

 

 

Patent Information:
Title App Type Country Serial No. Patent No. File Date Issued Date Expire Date Patent Status
CHECKPOINT BLOCKADE AND MICROSATELLITE INSTABILITY DIV: Divisional Japan 2019-057599   11/12/2015     Pending
Checkpoint Blockade and Microsatellite Instability DIV: Divisional Singapore 10201914022Q   11/12/2015     Pending
CHECKPOINT BLOCKADE AND MICROSATELLITE INSTABILITY DIV: Divisional Japan 2021-032226   11/12/2015     Pending
CHECKPOINT BLOCKADE AND MICROSATELLITE INSTABILITY DIV: Divisional Australia 2021202086   11/12/2015     Pending
Checkpoint Blockade and Microsatellite Instability DIV: Divisional Korea (South) 10-2021-7016870   11/12/2015     Pending
CHECKPOINT BLOCKADE AND MICROSATELLITE INSTABILITY DIV: Divisional China 202110966397X   11/12/2015     Pending
Checkpoint Blockade and Microsatellite Instability DIV: Divisional European Patent Office 22166660.5   11/12/2015     Pending
CHECKPOINT BLOCKADE AND MICROSATELLITE INSTABILITY DIV: Divisional Hong Kong 42022051364.2   11/12/2015     Pending
Checkpoint Blockade and Microsatellite Instability DIV: Divisional Korea (South) 10-2022-7013198   11/12/2015     Pending
Checkpoint Blockade and Microsatellite Instability PCT: Patent Cooperation Treaty Canada 2,966,660   11/12/2015     Pending
Checkpoint Blockade and Microsatellite Instability PCT: Patent Cooperation Treaty China 2015800615827   11/12/2015     Pending
CHECKPOINT BLOCKADE AND MICROSATELLITE INSTABILITY CON: Continuation United States 16/144,549 10,934,356 9/27/2018 3/2/2021 11/12/2035 Granted
CHECKPOINT BLOCKADE AND MICROSATELLITE INSTABILITY CON: Continuation United States 17/131,326 11,325,974 12/22/2020 5/10/2022 11/12/2035 Granted
CHECKPOINT BLOCKADE AND MICROSATELLITE INSTABILITY CON: Continuation United States 17/131,328 11,339,219 12/22/2020 5/24/2022 11/12/2035 Granted
CHECKPOINT BLOCKADE AND MICROSATELLITE INSTABILITY CON: Continuation United States 17/131,339 11,325,975 12/22/2020 5/10/2022 11/12/2035 Granted
CHECKPOINT BLOCKADE AND MICROSATELLITE INSTABILITY CON: Continuation United States 17/354,653 TRACK ONE!!!!!!! 6/22/2021     Pending
CHECKPOINT BLOCKADE AND MICROSATELLITE INSTABILITY CON: Continuation United States 17/354,656 TRACK ONE!!!!!!! 6/22/2021     Pending
CHECKPOINT BLOCKADE AND MICROSATELLITE INSTABILITY CON: Continuation United States 17/465,096 TRACK ONE!!!!!!! 9/2/2021     Pending
CHECKPOINT BLOCKADE AND MICROSATELLITE INSTABILITY CON: Continuation United States 17/465,101 TRACK ONE!!!!!!! 9/2/2021     Pending
CHECKPOINT BLOCKADE AND MICROSATELLITE INSTABILITY CON: Continuation United States 17/739,274 TRACK ONE!!!!!!! 5/9/2022     Pending
CHECKPOINT BLOCKADE AND MICROSATELLITE INSTABILITY CON: Continuation United States 17/739,278 TRACK ONE!!!!!!! 5/9/2022     Pending
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For Information, Contact:
Jeanine Pennington
jpennin5@jhmi.edu
410-614-0300
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