Revolution Medicines Presents Promising Phase 1 Data for Zoldonrasib in KRAS G12D Non-Small Cell Lung Cancer

Zoldonrasib demonstrates manageable safety profile and encouraging clinical activity in previously treated patients

Apr. 19, 2026 at 10:05pm

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An abstract, ghostly X-ray image showing the molecular structure of the KRAS G12D protein, visualized as a complex network of glowing lines and shapes against a dark background.Cutting-edge X-ray imaging reveals the intricate molecular structure of the KRAS G12D protein, a key target for Revolution Medicines' investigational cancer therapy zoldonrasib.Redwood City Today

Revolution Medicines announced updated Phase 1 clinical data for zoldonrasib, an oral RAS(ON) G12D-selective inhibitor, in patients with previously treated KRAS G12D non-small cell lung cancer (NSCLC). The data, presented at the 2026 AACR Annual Meeting, showed zoldonrasib was generally well-tolerated and demonstrated encouraging clinical activity in this patient population.

Why it matters

KRAS G12D is the most common oncogenic driver of human cancers, representing 4% of NSCLC cases. Patients with RAS G12D NSCLC have limited treatment options, as historical therapies like chemotherapy have offered limited benefit and significant toxicity. These promising Phase 1 results for zoldonrasib support its continued development as a potential targeted therapy for this high unmet medical need.

The details

In the Phase 1 RMC-9805-001 trial, 40 patients with KRAS G12D NSCLC were treated with the recommended Phase 2 dose of zoldonrasib 1200 mg once daily. Zoldonrasib demonstrated a manageable safety profile, with the most common treatment-related adverse events being nausea, vomiting, diarrhea, and rash, mostly Grade 1 in severity. In a subset of 27 patients previously treated with immune checkpoint inhibitors and platinum chemotherapy, the confirmed objective response rate was 52% and the disease control rate was 93%. Median progression-free survival was 11.1 months, with an estimated 12-month PFS rate of 48%.

  • The data presented are as of a December 1, 2025 data cutoff.
  • The results were highlighted in the official press program and featured in a plenary oral presentation at the 2026 AACR Annual Meeting on April 19, 2026.

The players

Revolution Medicines, Inc.

A late-stage clinical oncology company developing targeted therapies for patients with RAS-addicted cancers.

Jonathan Riess M.D.

Medical director of thoracic oncology at UC Davis Comprehensive Cancer Center and principal investigator for the RMC-9805-001 trial.

Alan Sandler, M.D.

Chief development officer of Revolution Medicines.

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What they’re saying

“Patients with RAS G12D non-small cell lung cancer remain a population with a significant unmet medical need for targeted therapeutic options. The manageable safety profile and evidence of clinical activity in this Phase 1 trial are encouraging and support the continued clinical development of zoldonrasib.”

— Jonathan Riess M.D., Medical director of thoracic oncology at UC Davis Comprehensive Cancer Center

“We believe these updated data further strengthen the profile of zoldonrasib as a potentially important targeted therapy for patients with RAS G12D non-small cell lung cancer where historical treatment options, such as chemotherapy, have offered limited benefit, and are often associated with considerable toxicity. The emerging profile supports advancing zoldonrasib across monotherapy and combination settings in lung cancer and other RAS G12D-driven cancers.”

— Alan Sandler, M.D., Chief development officer of Revolution Medicines

What’s next

Zoldonrasib is currently being evaluated as a monotherapy and in combination with other therapies, including Revolution Medicines' RAS(ON) multi-selective inhibitor daraxonrasib (RMC-6236), as well as standard of care regimens in lung and gastrointestinal cancers.

The takeaway

These promising Phase 1 results for zoldonrasib in KRAS G12D NSCLC, a patient population with limited treatment options, support the continued clinical development of this targeted therapy and its potential to address a significant unmet medical need.