First-line pembrolizumab (P), trastuzumab (T), capecitabine (C) and oxaliplatin (O) in HER2-positive metastatic esophagogastric adenocarcinoma (mEGA).

Media type: E-Article

Title: First-line pembrolizumab (P), trastuzumab (T), capecitabine (C) and oxaliplatin (O) in HER2-positive metastatic esophagogastric adenocarcinoma (mEGA)

Contributor: Janjigian, Yelena Yuriy; Chou, Joanne F.; Simmons, Marc; Momtaz, Parisa; Sanchez-Vega, Francisco; Shcherba, Marina; Ku, Geoffrey Yuyat; Won, Elizabeth; Chong, Curtis Robert; Gerdes, Hans; Kelsen, David Paul; Ilson, David H.; Aljallad, Kathrena; Segal, Michal Fani; Millang, Brittanie M; Schultz, Nikolaus; Shah, Pari M.; Solit, David B.; Capanu, Marinela; Hechtman, Jaclyn Frances

imprint: American Society of Clinical Oncology (ASCO), 2019

Language: English

DOI: 10.1200/jco.2019.37.4_suppl.62

ISSN: 0732-183X; 1527-7755

Keywords: Cancer Research ; Oncology

Origination:

Footnote:

Description: 62 Background: Trastuzumab stimulates HER2-specific T cell responses and increases tumor PD-L1 expression, and anti-PD-1 antibody can help enhance T cell-specific immunity of trastuzumab. Oxaliplatin can further enhance T-cells by activating dendritic cells. We conducted a phase II trial of pembrolizumab with chemotherapy/trastuzumab. Methods: Patients with previously untreated HER2 IHC 3+ or FISH+ tumors irrespective of PD-L1 status received intravenous P 200 mg flat dose, T 6 mg/kg (after 8 mg/kg load), O 130 mg/m2 every 3 weeks and oral C 850 mg/m2 2 weeks on/1 week off (or 5-FU continuous infusion). The primary endpoint was 6-months PFS; with target accrual of 37 patients. Secondary endpoints included safety, OS, ORR, exploratory biomarker analysis and 89Zr-trastuzumab PET. Results: 100% of the 24 evaluable pts had tumor regression (ranging from -22% to -100%). The RECIST 1.1 ORR was 83% [95%CI: 63%-95%] (17 PR , 3 CRs), median PFS 11.4 [95%CI: 6-15] months. In 31 pts evaluable for toxicity, common ( > 10%) adverse events included Gr 2 fatigue (35%), Gr 2/3 nausea (35%), Gr 2 diarrhea (26%), Gr2 AST/ALT elevation (16%), Gr2 neutropenia (16%). Immune related toxicities observed in 1 pt each: Gr 2 colitis, Gr 3 interstitial nephritis, Gr 3 AST/ALT elevation; and resolved with steroids. Of 21 patients with available material, 6 (29%) expressed PD-L1. Of these 6 patients, 5 had a PR while 1 had a CR. ERBB2 amplification was evident on NGS in 56% of pre-treatment tumors from 25 tested patients, while the remaining were ERBB2- by NGS likely due to tumor heterogeneity or low tumor content. Mutations in TP53 and alterations in KRAS occurred in 68% and 16%, respectively. To identify mechanisms of acquired resistance, patients are biopsied at progression. In 6 paired sample analysis, we identified two patients with loss of ERBB2 amp at progression. Conclusions: Updated survival, correlative studies and 89Zr-trastuzumab PET imaging will be presented. These promising preliminary safety and efficacy results led to initiation of a definitive phase III Keynote 811 trial. Clinical trial information: NCT02954536.

Access State: Open Access

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