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Trastuzumab Rezetecan in Human Epidermal Growth Factor Receptor 2–Expressing Advanced Gastric Cancer or Gastroesophageal Junction Adenocarcinoma and Colorectal Cancer: A Multicenter, Open-Label, Phase I Trial

May 1, 2026

Encouraging phase I signal for this HER2-targeted Antibody-drug conjugate (ADC) in heavily pretreated GI cancers, 45% overall response rate (ORR) and 16.3mo median overall survival (OS) in HER2-positive gastric compares favorably with T-DXd benchmarks, and the 40.5% objective response rate (ORR) with 22.7mo OS in HER2-positive colorectal cancer (CRC) is notable. The 2% ILD rate looks meaningfully better than T-DXd’s reported range, which could be a real differentiator. Hematologic toxicity is substantial but manageable. Small China-only phase I, but worth watching closely as this advances.

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Perioperative Durvalumab in Gastric and Gastroesophageal Junction Cancer

July 1, 2025

The MATTERHORN trial assessed patients with resectable gastric cancer/gastroesophageal junction cancer and assigned them 1:1 to perioperative durvalumab 1500 mg Q4W + FLOT (neoadjuvant and adjuvant) vs placebo + FLOT. Durvalumab + FLOT significantly improved 2-yr EFS (67.4% vs 58.5%) and increased pathological complete response (pCR) (19.2% vs 7.2%), with a numerically higher 2-year overall survival (OS) (75.7% vs 70.4%). Safety was comparable between arms (grade 3–4 AEs 71.6% vs 71.2%) with no excess surgical delays, unexpected toxicities or adjuvant initiation delays. Bottom line: Immunotherapy (IO) benefit appears linked to the FLOT backbone—as cis/FP + IO regimens have not consistently improved event-free survival (EFS)—and mature OS plus broader representation remain needed, but this looks like a meaningful advance.

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