KRAS-G12D inhibitor HRS-4642 plus chemotherapy in advanced KRAS G12D -mutant pancreatic cancer: a phase 1b/2 trial.

While most investigational KRAS-G12D inhibitors are oral small molecules limited by gastrointestinal toxicities and suboptimal tumor exposure, HRS-4642 is a new, high‑affinity, noncovalent KRAS-G12D inhibitor.

This phase 1b/2 study evaluated HRS-4642 in combination with nab-paclitaxel and gemcitabine (AG) in patients with advanced KRAS G12D -mutant pancreatic ductal adenocarcinoma.

Grade ≥3 treatment-related adverse events (treatment-related adverse events) occurred in 90.3% patients, primarily hematologic toxicities consistent with AG chemotherapy.