Merck...announced that the European Commission has approved KEYTRUDA, Merck’s anti-PD-1 therapy, as monotherapy for the treatment of microsatellite instability-high (MSI-H) or deficient mismatch repair (dMMR) tumors in adults with...unresectable or metastatic gastric, small intestine or biliary cancer, who have disease progression on or following at least one prior therapy.

Pembrolizumab is recommended as an option for treating tumours with high microsatellite instability (MSI) or mismatch repair (MMR) deficiency in adults with…unresectable or metastatic gastric, small intestine or biliary cancer that has progressed during or after 1 therapy

Gastric Cancer: Preferred Regimens...MSI-H/dMMR tumors…Fluoropyrimidine (fluorouracil or capecitabine), oxaliplatin, and pembrolizumab…

Preferred Regimens: Pembrolizumab for second-line or subsequent therapy for MSI-H or dMMR tumors

Pembrolizumab monotherapy in KEYNOTE-059, pembrolizumab monotherapy or chemotherapy (paclitaxel) in KEYNOTE-061, and pembrolizumab monotherapy, pembrolizumab plus chemotherapy (cisplatin and 5-fluorouracil or capecitabine)...In KEYNOTE-062, the ORR was 57.1% for pembrolizumab , 64.7% for pembrolizumab plus chemotherapy, and 36.8% for chemotherapy....MSI-H status may be a biomarker for pembrolizumab therapy among patients with advanced G/GEJ cancer...

...- Participants' tumor must have an MSI-H or dMMR status according to institutional guidelines and/or according to the College of American Pathologists, determined at any time prior to enrolment....

...(Only Cohort B) confirmed as MSI-H via the PCR or IHC staining by institutional standard....

...Microsatellite Instability-High Cancer 9....

...- Subjects with histologically confirmed melanoma, NSCLC, transitional cell carcinoma of the GU tract, TNBC, SCCHN, ovarian cancer, MSI high colorectal cancer (CRC), RCC, gastric cancer, HCC and DLBCL (Phase 2)....

...Previously treated participants with solid tumors (NSCLC, melanoma, HNSCC, RCC, HCC, gastroesophageal carcinomas, UC, or CRC [MSI-H]) for whom, in the opinion of the investigator, there is...

...Consistent with high-frequency microsatellite instability MSI-H 2....

Of the 33 patients, 12 were MSI-H, 3 EBV (+), and 27 had PDL1 expression with CPS >/= 1%. Tumors were of advanced clinical stage with 84.8% ≥ cT3 and 57.6% cN(+). All patients received two cycles of neoadjuvant pembrolizumab...treatment effect was seen in 46%, down-staging in 50%, and complete pathologic response seen in 3 patients, 2 of whom has MSI-H tumors and one whose tumor was PDL1+...This study presents a novel and effective paradigm for the management of localized gastric cancer...

We retrospectively reviewed patients with RMGC, whose third-line treatment started between July 2019 and June 2021 at 17 centers in South Korea. The ICI group included patients who received nivolumab or pembrolizumab...microsatellite instability-high (MSI-H)/mismatch repair-deficient (MMR-D) tumor was an independent prognostic factor for superior OS. The ICI group showed significantly longer OS than the irinotecan-based chemotherapy group in patients without peritoneal metastasis [HR 0.54 (95% CI 0.30-0.99); P=0.047)].

Three hundred and fifty-one patients with various tumor types were enrolled in KEYNOTE-158 cohort K. The most common tumor types were endometrial (22.5%), gastric (14.5%), and small intestine (7.4%)...ORR among 321 patients in the efficacy population (patients who received ≥1 dose of pembrolizumab enrolled ≥6 months before the data cutoff date) was 30.8% (95% CI, 25.8‒36.2). Median duration of response was 47.5 months (range, 2.1+ to 51.1+ months). Median progression-free survival was 3.5 months (95% CI, 2.3‒4.2 months) and median overall survival was 20.1 months (95% CI, 14.1‒27.1 months)...Pembrolizumab demonstrated clinically meaningful and durable benefit, with high ORR of 30.8%, long median duration of response of 47.5 months, and manageable safety across a range of heavily pretreated, advanced MSI-H/dMMR noncolorectal cancers, providing support for use of pembrolizumab in this setting.

...Merck...today announced the European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) has adopted a positive opinion recommending approval of KEYTRUDA, Merck’s anti-PD-1 therapy, as monotherapy for the treatment of the following microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR) tumors in adults with: unresectable or metastatic colorectal cancer after previous fluoropyrimidine-based combination therapy; advanced or recurrent endometrial carcinoma who have disease progression on or following prior treatment with a platinum-containing therapy in any setting and who are not candidates for curative surgery or radiation; unresectable or metastatic gastric, small intestine or biliary cancer who have disease progression on or following at least one prior therapy....The CHMP’s recommendation was based on results from the Phase 2 KEYNOTE-158 trial as well as results from the Phase 2 KEYNOTE-164 trial...

Early results from our phase 2 clinical trial show immunotherapy to be well tolerated with limited toxicity...Following 2 cycles of pembrolizumab, 2 patients with MSI-H had complete pathologic response.

...6 (20%) dMMR/MSI-H/TMB-H (received sintilimab, pembrolizumab, tislelizumab or nivolumab, combined with antivascular or not, cohort C)...In cohort C, ORR was 17% (1/6), DCR was 67% (4/6), mPFS and mOS was 1.9 months and 6.8 months, respectively.

We conducted a phase II trial of pembrolizumab in patients with advanced MSI-H gastric cancer and included serial...nonsynonymous mutations correlated with antitumor activity and prolonged progression-free survival (PFS...MSI-H gastric cancer and may inform development of strategies to enhance responsiveness.

In pts with MSI-H tumors, OS and PFS were prolonged with pembro vs chemo, with higher ORR (Table).

Our study demonstrates the clinical benefit of anti-programmed death-1 therapy with pembrolizumab among patients with previously treated unresectable or metastatic MSI-H/dMMR noncolorectal cancer. Median progression-free survival and median overall survival for the seven largest tumor cohorts are summarized in Table 3.