Jiujie Cui MD PhD, CSCO 2026: Early Findings Show KRAS-G12D Inhibitor More than Doubles Median Overall Survival in Patients with Advanced Pancreatic Cancer

Early Findings Show KRAS-G12D Inhibitor More than Doubles Median Overall Survival in Patients with Advanced Pancreatic Cancer

An interview with:

Jiujie Cui MD PhD, Medical Oncologist, Renji Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China

JINAN, China—A highly selective drug that inhibits the predominant oncogenic driver (the KRAS-G12D mutation) in advanced pancreatic ductal adenocarcinoma, and minimizes side effects, has shown big promise for keeping patients alive and progression-free. This was in early trial results reported at the 2026 Annual Meeting of the Chinese Society of Clinical Oncology.

In phase 1b/2 study results, Chinese researchers reported marked improvements in outcomes that mirror the 2026 findings from the USA reported in the New England Journal of Medicine with a multi-selective RAS inhibitor. Peter Goodwin heard the latest from the study first author: medical oncologist Jiujie Cui MD PhD, from Renji Hospital at Shanghai Jiaotong University School of Medicine, in Shanghai, China.

AUDIO JOURNAL OF ONCOLOGY, Jiujie Cui MD PhD:

IN: “I’m here at ….

OUT:…….for the Audio Journal of Oncology, I’m Peter Goodwin. 10:24 secs

Reference:

https://www.nature.com/articles/s41591-026-04538-9

KRAS-G12D inhibitor HRS-4642 plus chemotherapy in advanced KRASG12D-mutant pancreatic cancer: a phase 1b/2 trial

Abstract:

KRASG12D is the predominant oncogenic driver in pancreatic ductal adenocarcinoma (PDAC). 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. Formulated as a liposomal nanoparticle for intravenous administration, it is designed to enhance tumor accumulation and prolong the duration of target inhibition. This phase 1b/2 study evaluated HRS-4642 in combination with nab-paclitaxel and gemcitabine (AG) in patients with advanced KRASG12D-mutant PDAC. As of 5 December 2025, 68 patients were screened and 31 (1 previously treated patient and 30 treatment-naive patients) were enrolled and treated.

In the phase 1b portion, no dose-limiting toxicities were observed, and the starting dose (500 mg on day 1 and 1,200 mg on day 8, every 3 weeks) was selected as the recommended phase 2 dose.

In the phase 2 portion, with a median follow-up of 12.3 months (95% confidence interval (CI) = 12.2–13.0), the primary endpoint was met—the confirmed objective response rate in 30 treatment-naive patients was 63.3% (95% CI = 43.9–80.1).

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

No TRAEs led to treatment discontinuation or death. In conclusion, HRS-4642 combined with AG demonstrates promising antitumor activity and a manageable safety profile in advanced KRASG12D-mutant PDAC, supporting further investigation.