Antitumor activity of margetuximab (M) plus pembrolizumab (P) in patients (pts) with advanced HER2+ (IHC3+) gastric carcinoma (GC).

• DOI: 10.1200/jco.2019.37.4_suppl.65
• Publication Date: 2019-01-29T23:13:19Z
• Authors: Daniel V.T. Caten...; Kian Huat Lim; Hope Elizabeth Ur...; Yoon-Koo Kang; Matthew C.H. Ng; Philip Jordan Gold; Peter C. Enzinger; Keun Wook Lee; Jill Lacy; Se Hoon Park; Jennifer Yen; Justin Odegaard; Aleksandra Franovic; Jan E. Baughman; Aisha Wynter-Horton; Francine Chen; Paul A. Moore; Tony Wu; Jan Kenneth David...; Yung-Jue Bang
• Keywords: Ramucirumab; Pneumonitis

65 Background: Trastuzumab (T) + chemo is standard first-line therapy (tx) for HER2+ gastroesophageal adenocarcinoma (GEA) pts, though progression ensues in 6-8 months. The approved second-line tx ramucirumab +/- paclitaxel (R+PAC). Pts with GC are less responsive to R+PAC than junction (GEJ) particular GC, and no anti-HER2 agents post-T setting. We report results of combination M+P pts describe a biological rationale this population. M an mAb Fc optimized enhanced binding activating FcgRIIIa (CD16A) decreased inhibitory FcgRIIb (CD32B). demonstrated Fc-dependent MoA, including ADCC. Methods: HER2+, PD-L1-unselected, GEA post T received (15 mg/kg) P (200 mg) Q3wk. Safety, objective response rate (ORR), median overall & progression-free survival (mOS, mPFS), disease control (DCR), circulating tumor DNA, PD-L1 expression were assessed. Results: To date, 66 dosed; 35 (53%) 31 (47%) GEJ. Overall, 12/66 (18.2%) had tx-related adverse events ≥ grade 3; 5 drug-related SAEs: dehydration, diabetic ketoacidosis, hypotension pneumonitis, each single event, 2 autoimmune hepatitis. Eligibility was based on archival HER2 expression; exploratory endpoint measured retention by ERBB2 ctDNA. lost 23/56 (41.1%) tested T. higher versus GEJ (65.8% vs. 44.8%) IHC 3+ vs 2+ tumors (61.7% 47.4%, respectively). Furthermore, GEJ, 53.3 33.3%, respectively. This coincided more responses IHC3+ ORR 12/29 (41.4%; 95% CI 23.5-61.1), DCR 21/29 (72.4%; 52.8-87.3), mPFS 5.5 months (95% 2.3-7.6), mOS not reached, lower bound 9.1 CI. Enrollment additional 25 enriched ongoing. Conclusions: Results suggest that M+P, chemo-free regimen, demonstrates acceptable tolerability has encouraging preliminary activity GEA, specifically who retain amp prior tx. Clinical trial information: NCT02689284.