Pembrolizumab (Pembro) In Microsatellite Instability-High (Msi-H) Advanced Gastric/Gastroesophageal Junction (G/Gej) Cancer By Line Of Therapy

430 Background: Pembro has demonstrated promising antitumor activity in patients (pts) with advanced G/GEJ cancer with PD-L1 CPS ≥1 and CPS ≥10 irrespective of MSI-H status. Here, we examine the antitumor activity of pembro monotherapy vs chemo in pts with MSI-H, advanced G/GEJ cancer in KEYNOTE (KN)-059 (NCT02335411), KN061 (NCT02370498), and KN062 (NCT02494583). Methods: Eligible pts with advanced G/GEJ cancer with ≥2 prior therapies (KN059 cohort 1; 3L+), 1 prior therapy (KN061; 2L), or no prior therapy (KN062; 1L) were enrolled. In KN059 cohort 1, pts received pembro only. In KN061 pts were randomized to pembro or paclitaxel (chemo), and in KN062 to pembro, pembro + cisplatin+5-FU/cape (chemo), or chemo. Pts received pembro 200 mg Q3W for up to 2 y. MSI-H status was determined centrally by PCR. Endpoints included OS, PFS, ORR, and safety. Data cutoff dates were Aug 8, 2018 (KN059), Oct 26, 2017 (KN061), and Mar 26, 2019 (KN062). Results: At data cutoff, 259 pts (n = 7 [3%] MSI-H) had enrolled in KN059 cohort 1 (3L+), 592 (27 [5%] MSI-H]) in KN061 (2L), and 763 (50 [7%] MSI-H] in KN062 (1L). Median follow-up was 5.6 mo, 7.9 mo, and 11.3 mo, respectively. For the overall study populations, median OS was 5.5 mo for pembro (3L+), 6.7 mo vs 8.3 mo for pembro vs chemo (2L), and 10.6 mo vs 11.0 mo for pembro vs chemo (1L). Median PFS was 2.0 mo (3L+), 1.5 vs 4.1 mo (2L), and 2.0 vs 6.4 mo (1L). ORR was 11.6% (3L+), 11.1% vs 12.5% (2L), and 14.8% vs 37.2% (1L), with median DOR of 16.1 mo, 18.0 vs 5.5 mo, and 13.7 vs 6.8 mo. In pts with MSI-H tumors, OS and PFS were prolonged with pembro vs chemo, with higher ORR (Table). Conclusions: As with PD-L1 expressers, MSI-H status is a predictive biomarker for pembro monotherapy in advanced G/GEJ cancer irrespective of line of therapy. Clinical trial information: (KN)-059 (NCT02335411), KN061 (NCT02370498), and KN062 (NCT02494583). Merck & Co., Inc., Kenilworth, NJ, USA.[Table: see text]