IMAB362, a chimeric monoclonal antibody that mediates specific killing of cancer cells expressing the tight junction protein Claudin18.2 (CLDN18.2) by activation of immune effector mechanisms, has demonstrated single-agent activity and tolerability in patients (pts) with heavily pretreated gastric cancer.
Pts with advanced/recurrent gastric and GEJ cancer were centrally evaluated for CLDN18.2 expression by immunohistochemistry (CLAUDETECT® 18.2 Histology Kit). Eligible pts had a CLDN18.2 expression of ≥2+ in ≥40% tumor cells, an ECOG PS of 0–1 and were not eligible for trastuzumab. Pts were randomized 1:1 to first-line EOX (epirubicin 50 mg/m2 and oxaliplatin 130 mg/m2 d1, and capecitabine 625 mg/m2 bid, d1–21; qd22) with or without IMAB362 (loading dose 800 mg/m2, then 600 mg/m2 d1, qd21). An exploratory arm (N = 85) was added to investigate a higher dose IMAB362 (1000 mg/m2) plus EOX. The primary study endpoint was PFS (Arm1 vs 2, 70% power, hazard ratio [HR] 0.72, 1-sided p = 0.1). Here we present the final study results.
Of 686 biomarker-assessable pts, 334 pts (48%) were tested CLDN18.2+ per protocol criteria. Of those, 161 pts (median age 58 years; 80% gastric, 16% GEJ, 4% esophageal; 44% diffuse, 33% intestinal) were randomized into Arms 1 and 2. IMAB362 plus EOX improved PFS (median 4.8 vs 7.9 months; HR 0.47; 95% confidence interval [CI] 0.31–0.70, 1-sided p = 0.0001), OS (median 8.4 vs 13.2 months; HR 0.51, 95% CI 0.36–0.73, p = 0.0001) and ORR (28% vs 43%) compared to EOX. Common IMAB362-related adverse events included vomiting, neutropenia, and anemia, which were mostly of NCI-CTCAE grade 1 or 2. Grade 3/4 events were not significantly increased by IMAB362.
This final analysis confirms that addition of IMAB362 to first-line chemotherapy provides a clinically relevant benefit in patients with inoperable or recurrent gastric and GEJ cancer.
Clinical trial identification
Legal entity responsible for the study
Ganymed Pharmaceuticals AG
Ganymed Pharmaceuticals AG
M. Schuler: Corporate-sponsored research: BI, BMS, Novartis. Honoraria/Consultancy: Alexion, AstraZeneca, BI, BMC, Celgene, IQWig, GSK, Lilly, Novartis, Pfizer. Patents and employment: University Duisburg-Essen. S.–E. Al-Batran: Advisory role: Merck, Roche, Celgene, Lilly, Nordic Pharma. Speaker: Roche, Celgene, Lilly, Nordic Pharma. Research grants: Merck, Roche, Celgene, Vifor, Medac, Hospira, Lilly. F. Lordick: Research support: GSK, Fresenius Biotech. Lecture and Advisory honoraria: Amgen, Biontech, BMS, Eli Lilly, Ganymed, Merck-Serono, Merck-MSD, Nordic, Roche. Travel support: Amgen, Bayer, Roche, Taiho. C. Huber: Stock owner of Ganymed and of BioNTech shares. Member of Ganymed's and of BioNTech's supervisory board. Scientific Advisor of Ganymed, of BioNTech and of TRON. Executive board member of CI3-Cluster. Ö. Türeci: Stock ownership: Ganymed Pharmaceuticals AG. Advisory board: Ganymed Pharmaceuticals AG. Patents: Ganymed Pharmaceuticals AG, BioNTech Holding. Employment, leadership role: Ganymed Pharmaceuticals AG. U. Sahin: Stock ownership: BioNTech Holding Advisory Board: Ganymed Pharmaceuticals AG. Patents: Ganymed Pharmaceuticals AG, BioNTech Holding. Employment, leadership role: BioNTech Holding. All other authors have declared no conflicts of interest.
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