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Triple-Drug Combo Eradicates Pancreatic Tumors in Mice, Peer-Reviewed Study Finds

Researchers say the preclinical data can steer trial planning after coordinated KRAS pathway blockade kept tumors from returning in patient-derived and orthotopic models.

Two cancer-infected laboratory rats stand atop wire mesh next to a syringe filled with Cisplatin, in a lab at Michigan State University. The healthy looking rat was treated with Cisplatin, while the unhealthy one was not. East Lansing, Michgan.
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Most pancreatic cancers are driven by a faulty gene called KRAS. (Photo: Getty)
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Overview

  • Scientists at Spain’s CNIO, led by Mariano Barbacid, achieved complete and durable regressions of pancreatic ductal adenocarcinoma in multiple mouse models with no recurrence beyond 200 days and minimal observed toxicity.
  • The regimen pairs daraxonrasib (RMC-6236) with afatinib and the STAT3 degrader SD36 to inhibit KRAS, EGFR/HER2 and STAT3 nodes that tumors use to evade single-drug therapies.
  • Findings were consistent across orthotopic models and patient-derived xenografts and were published after peer review in the Proceedings of the National Academy of Sciences (PNAS).
  • The authors stress the results are preclinical, saying dose optimization, safety evaluation, manufacturing and regulatory steps must precede Phase I testing, and no human trials are underway as of January 29, 2026.
  • KRAS mutations drive about 90% of pancreatic ductal adenocarcinomas and enable rapid resistance, and separate Duke University work using a biodegradable radioactive gel also produced sustained mouse regressions, highlighting parallel preclinical momentum.