PD-1 blockade in mismatch repair deficient non-colorectal gastrointestinal cancers.

Cancers of the Pancreas, Small Bowel, and Hepatobiliary Tract
Session Type and Session Title: 
Oral Abstract Session: Cancers of the Pancreas, Small Bowel, and Hepatobiliary Tract
Poster Session B: Cancers of the Pancreas, Small Bowel, and Hepatobiliary Tract
Abstract Number: 


Poster Board Number: 
Poster Session B Board #A5
J Clin Oncol 34, 2016 (suppl 4S; abstr 195)
Dung T. Le, Jennifer N. Uram, Hao Wang, Holly Kemberling, Aleksandra Eyring, Bjarne Bartlett, Richard M. Goldberg, Todd S. Crocenzi, George A. Fisher, James J. Lee, Tim F. Greten, Dan Laheru, Nilofer Saba Azad, Ross C. Donehower, Brandon Luber, Minori Koshiji, James R. Eshleman, Robert A Anders, Bert Vogelstein, Luis A. Diaz; The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, MD; The Ohio State University Comprehensive Cancer Center, Arthur G. James Cancer Hospital, Richard J. Solove Research Institute, Columbus, OH; Providence Cancer Center, Portland, OR; Stanford University School of Medicine, Stanford, CA; University of Pittsburgh, Pittsburgh, PA; National Cancer Institute at the National Institutes of Health, Bethesda, MD; Johns Hopkins Cancer Center, Baltimore, MD; Merck & Co., Inc., Kenilworth, NJ; Johns Hopkins University School of Medicine, Baltimore, MD

Abstract Disclosures


Background: Mismatch repair (MMR) deficient tumors harbor hundreds to thousands of mutations that may produce neoantigens that can be recognized and targeted by T cells. We have shown that MMR deficiency can serve as a predictive biomarker for selection of tumors across tumor histologies that may respond to programmed death-1 (PD-1) blockade. MMR deficiency is present in 15% of colorectal (CRC) however is also detected in 2-20% of gastric, small bowel, and hepatobiliary cancers. Methods: We conducted a phase II study to evaluate anti-PD-1, pembrolizumab, in patients with previously-treated, progressive, advanced cancer. Twenty-one patients with MMR deficient tumors were enrolled onto the non-CRC cohort with an additional 50 patient expansion underway. The pembrolizumab dose is 10mg/kg intravenously every 2 weeks. Objective response rate (ORR), progression-free survival (PFS), and overall survival (OS) will be reported in at least the first 17 patients with non-CRC gastrointestinal (GI) cancers. Results: As of September 18, 2015, 17 patients with non-CRC GI cancers have been enrolled on the protocol with additional patients identified. The diseases represented are ampullary (N=4), pancreas (N=4), biliary (N=3), small bowel (N=3), and gastric (N=3) cancers. For the 10 evaluable patients at the time of abstract admission, ORR is 50 % (N=5/10), disease control rate is 70% (N=7/10), OS is 21 months and the median duration of response (range 5.5-17+ months) and PFS have not been reached. The median follow up duration is 7.6 months. Conclusions: PD-1 blockade shows promising activity in mismatch repair deficient GI cancers. Clinical trial information: NCT01876511