HRS-4642 plus chemotherapy ± adebrelimab as perioperative therapy in KRAS G12D-mutant pancreatic cancer: Preliminary results of a phase 2 study

HRS-4642

Patient / Population Intervention / Exposure Comparison Outcome

In patients with resectable or borderline resectable KRAS G12D-mutant pancreatic cancer, perioperative HRS-4642 plus gemcitabine and nab-paclitaxel, with or without adebrelimab, produced objective responses in 63% and 87% of patients with manageable toxicity.

N

60patients

Design

Open-label, prospective, non-randomised phase 2 trial with a BOP2 design in treatment-naive resectable or borderline resectable KRAS G12D-mutant pancreatic cancer, giving perioperative HRS-4642 plus gemcitabine and nab-paclitaxel without (Cohort 1) or with (Cohort 2) adebrelimab (NCT06587061, NCT07131514).

Endpoint

Objective response rate per RECIST v1.1 and safety (co-primary).

ResultObjective response rate 63% (19 PR) in Cohort 1 vs 87% (26 PR) in Cohort 2, with tumour shrinkage in all patients. Surgery was performed in 23 vs 29 patients. Among resected patients the R0 resection rate was 100% and the MPR rate 17% in both cohorts. Six-month EFS rates were 87% vs 96%. Survival data remain immature. All patients with baseline CA19-9 > ULN had a reduction of ≥50%. All patients had treatment-related adverse events: grade ≥3 in 47% vs 53%, most commonly neutropenia and leukopenia. No TRAEs were fatal or precluded surgery.

Shen B, Wen C, Zou S, et al. Presented at ESMO Congress 2026, abstract LBA85, 26 October. Not yet published.

Discussion & critique

In two small cohorts of 30 patients each, the abstract reports high radiological response and R0 resection rates with no treatment-related deaths and no patient kept from surgery by toxicity. The cohorts were not randomised and were treated open label, so the higher response rate with adebrelimab cannot be read as a controlled comparison, and response rate is a surrogate. The major pathological response rate of 17% is modest next to the radiological responses, only six-month EFS is given, survival is immature, and four Cohort 1 patients were still in neoadjuvant treatment at data cut-off. The abstract does not say how patients were assigned to cohorts or how many had borderline resectable disease, and its Methods describe resectable disease only.