2812 - Margetuximab (M) + pembrolizumab (P) for treatment of patients (pts) with HER2+ gastroesophageal adenocarcinoma (GEA) post-trastuzumab (T): Survival analysis

Background

Current standard of care (SOC) in 2L GEA, ramucirumab + taxane, has median progression free survival (mPFS) of 4.4 months (m) and median overall survival (mOS) of 9.6 m. Chemotherapy-backbone HER2-targeted agents tested in 2L HER2+ GEA TyTAN and GATSBY studies showed mPFS and mOS ranged 2.4-5.4 months (m), and 7.1-11.2 m. P, in 2L KN061, showed mPFS and mOS of 1.5 m and 9.1 m in GEA pts with PD-L1 CPS >1, and both were lower for PD-L1 all-comers. M is an investigational anti-HER2 Fc-optimized monoclonal antibody that can coordinate activation between innate and adaptive immunity. In pts treated with M+P, we previously reported ORR of 33% in HER-2 IHC-3+ gastric cancer (GC) pts and over 50% in pts with HER-2+/PD-L1+ tumors.

Methods

HER2+ PD-L1 unselected 2L GEA pts (N = 86) were enrolled post progression on T-based therapy (tx) and treated with M (15 mg/kg) and P (200 mg) IV Q3wk. We report mPFS and mOS in the overall expansion cohort and in biomarker subgroups including archival PD-L1 and HER2 IHC, ERRB2 ctDNA (prior to 2L tx), and tumor site (GC vs junction [GEJ]).

Results

Median duration of tx was 3.8 m (range 0.7-26.5), with median follow-up 11.3 m (range 1.6-28.6). Pt characteristics (n,%) included: GC 60 (70%), HER2 IHC3+ 68 (79%), PD-L1 CPS>1 32 (37%), ERBB2 ctDNA+ 46 (53%), and MSI-high 1 (1%). In overall GEA pts, mPFS was 3.5 m (95% CI 1.64-4.76), and mOS was 13.9 m (95% CI 9.26-16.82); OS rates at 6/12/18/24 m were 77/57/35/32%, respectively. In GEA HER2 IHC3+ pts, mPFS was 4.5 m (95%CI 2.7-7.5) and mOS was 16.8 m (95%CI 12.23-not reached (NR)). OS rates at 6/12/18/24 m were 85/66/48/44%, respectively; IHC3+ GC (54 [63%]) showed mPFS of 4.7 m (95% CI 2.73-7.49) and mOS NR (95% CI 12.25-NR). IHC3+/ctDNA+ confirmation GEA (38 [44%]) showed mPFS 7.5 m (95% CI 3.5-12.4) and mOS NR (13.27-NR), and IHC3+/ctDNA+ GC (31 [36%]) showed mPFS 5.6 m (95% CI 2.73-8.34) and mOS NR (12.48 – NR). Median PFS and mOS were lower in GEJ: 1.5 m (1.38, 4.34) and 9.2 m (5.26, 15.41), respectively.

Conclusions

In this study, M+P, a chemotherapy-free regimen, demonstrated acceptable tolerability in HER2+ GEA pts post-T, with extension of time-to-event endpoints compared to historical experience with SOC regimens, and checkpoint inhibitors alone.

Clinical trial identification

NCT02689284.

Editorial acknowledgement

Legal entity responsible for the study

MacroGenics, Inc.

Funding

MacroGenics, Inc.

Disclosure

D.V. Catenacci: Honoraria (self), Advisory / Consultancy: Amgen; Honoraria (self), Advisory / Consultancy: Bristol-Myers Squibb; Honoraria (self): Five Prime Therapeutics; Honoraria (self), Speaker Bureau / Expert testimony: Foundation Medicine; Honoraria (self), Advisory / Consultancy: Genentech/Roche; Honoraria (self): GenMab; Honoraria (self): Gritstone Oncology; Honoraria (self), Speaker Bureau / Expert testimony: Guardant Health; Honoraria (self), Advisory / Consultancy: Lilly; Honoraria (self), Advisory / Consultancy: Merck; Honoraria (self): NantOmics; Honoraria (self): OncoPlex Diagnostics; Honoraria (self), Advisory / Consultancy: Taiho Pharmaceutical; Advisory / Consultancy: Astellas Pharma. H. Park: Research grant / Funding (institution): Amgen; Research grant / Funding (institution): AstraZeneca; Research grant / Funding (institution): Bayer; Research grant / Funding (institution): BeiGene; Research grant / Funding (institution): Bristol-Myers Squibb; Research grant / Funding (institution): Daiichi Sankyo; Research grant / Funding (institution): EMD Serono; Research grant / Funding (institution): Gilead Sciences; Research grant / Funding (institution): Incyte; Research grant / Funding (institution): Lilly; Research grant / Funding (institution): MacroGenics; Research grant / Funding (institution): MedImmune; Research grant / Funding (institution): Medivation; Research grant / Funding (institution): Merck; Research grant / Funding (institution): Millennium; Research grant / Funding (institution): Novartis; Research grant / Funding (institution): Pfizer; Research grant / Funding (institution): Puma Biotechnology; Research grant / Funding (institution): Regeneron; Research grant / Funding (institution): Roche; Research grant / Funding (institution): Taiho Pharmaceutical; Research grant / Funding (institution): Vertex. H. Uronis: Shareholder / Stockholder / Stock options, Full / Part-time employment: GeneCentric; Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: Bristol-Myers Squibb; Research grant / Funding (institution): Advaxis; Research grant / Funding (institution): Genentech/Roche; Research grant / Funding (institution): Lycera; Research grant / Funding (institution): MacroGenics; Research grant / Funding (institution): Merck. Y. Kang: Advisory / Consultancy: Bristol-Myers Squibb; Advisory / Consultancy, Research grant / Funding (self): DAE HWA Pharmaceutical; Advisory / Consultancy: Lilly/ImClone; Advisory / Consultancy: Merck/Serono; Advisory / Consultancy: Ono Pharmaceutical; Advisory / Consultancy: Roche/Genentech; Advisory / Consultancy: Taiho Pharmaceutical; Research grant / Funding (self): LSK Biopharma. M.C.H. Ng: Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: MSD Oncology; Honoraria (self), Travel / Accommodation / Expenses: Taiho Pharmaceutical; Advisory / Consultancy: Bristol-Myers Squibb; Research grant / Funding (institution): ASLAN Pharmaceuticals. P. Enzinger: Advisory / Consultancy: Astellas Pharma; Advisory / Consultancy: Five Prime Therapeutics; Advisory / Consultancy: Merck; Advisory / Consultancy: Taiho Pharmaceutical. K.W. Lee: Research grant / Funding (institution): Array BioPharma; Research grant / Funding (institution): ASLAN Pharmaceuticals; Research grant / Funding (institution): AstraZeneca/MedImmune; Research grant / Funding (institution): Five Prime Therapeutics; Research grant / Funding (institution): Green Cross Corp; Research grant / Funding (institution): LSK BioPharma; Research grant / Funding (institution): MacroGenics; Research grant / Funding (institution): Merck KGaA; Research grant / Funding (institution): MSD; Research grant / Funding (institution): Ono Pharmaceutical; Research grant / Funding (institution): Pfizer; Research grant / Funding (institution): Pharmacyclics; Honoraria (self): Bristol-Myers Squibb; Honoraria (self): Lilly; Research grant / Funding (institution): ALX Oncology. K.H. Lim: Research grant / Funding (institution): Amgen; Research grant / Funding (institution): AstraZeneca; Research grant / Funding (institution): Bayer; Research grant / Funding (institution): BeiGene; Research grant / Funding (institution): Bristol-Myers Squibb; Research grant / Funding (institution): Daiichi Sankyo; Research grant / Funding (institution): EMD Serono; Research grant / Funding (institution): Gilead Sciences; Research grant / Funding (institution): Incyte; Research grant / Funding (institution): Lilly; Research grant / Funding (institution): MacroGenics; Research grant / Funding (institution): MedImmune; Research grant / Funding (institution): Medivation; Research grant / Funding (institution): Merck; Research grant / Funding (institution): Millennium; Research grant / Funding (institution): Novartis; Research grant / Funding (institution): Pfizer; Research grant / Funding (institution): Puma Biotechnology; Research grant / Funding (institution): Regeneron; Research grant / Funding (institution): Roche; Research grant / Funding (institution): Taiho Pharmaceutical; Research grant / Funding (institution): Vertex. J. Lacy: Advisory / Consultancy: AstraZeneca; Advisory / Consultancy: Celgene; Advisory / Consultancy: KeyQuest Health; Advisory / Consultancy: Navigant Consulting; Advisory / Consultancy: Sirtex Medical; Travel / Accommodation / Expenses: Lilly. S.H. Park: Advisory / Consultancy: Lilly. K. Huber: Full / Part-time employment: MacroGenics, Inc. A. Wynter-Horton: Shareholder / Stockholder / Stock options, Full / Part-time employment: MacroGenics, Inc. J. Nordstrom: Shareholder / Stockholder / Stock options, Full / Part-time employment: MacroGenics, Inc. T. Wu: Shareholder / Stockholder / Stock options, Full / Part-time employment: MacroGenics, Inc. J. Wigginton: Leadership role, Shareholder / Stockholder / Stock options, Full / Part-time employment: MacroGenics, Inc. J. Baughman: Shareholder / Stockholder / Stock options, Full / Part-time employment: MacroGenics, Inc. M. Rosales: Shareholder / Stockholder / Stock options, Full / Part-time employment: MacroGenics, Inc. J. Davidson-Moncada: Shareholder / Stockholder / Stock options, Full / Part-time employment: MacroGenics, Inc. Y. Bang: Advisory / Consultancy, Research grant / Funding (institution): AstraZeneca/MedImmune; Advisory / Consultancy, Research grant / Funding (institution): Bayer; Advisory / Consultancy, Research grant / Funding (institution): Beigene; Advisory / Consultancy, Research grant / Funding (institution): Green Cross; Advisory / Consultancy: Hanmi; Advisory / Consultancy, Research grant / Funding (institution): Merck Serono; Advisory / Consultancy, Research grant / Funding (institution): MSD Oncology; Advisory / Consultancy, Research grant / Funding (institution): Novartis; Advisory / Consultancy: Samyang; Advisory / Consultancy, Research grant / Funding (institution): Taiho Pharmaceutical; Research grant / Funding (institution): Astellas Pharma; Research grant / Funding (institution): AstraZeneca/MedImmune; Research grant / Funding (institution): Boehringer Ingelheim; Research grant / Funding (institution): Boston Biomedical; Research grant / Funding (institution): Bristol-Myers Squibb; Research grant / Funding (institution): Genentech/Roche; Research grant / Funding (institution): GlaxoSmithKline; Research grant / Funding (institution): Lilly; Research grant / Funding (institution): MacroGenics; Research grant / Funding (institution): Merck Serono; Research grant / Funding (institution): Ono Pharmaceutical; Research grant / Funding (institution): Pfizer; Research grant / Funding (institution): Takeda. All other authors have declared no conflicts of interest.