Revolution Medicines presented updated Phase 1 data for its KRAS G12D‑selective inhibitor zoldonrasib (RMC‑9805) at the AACR Annual Meeting. The RMC‑9805‑001 trial enrolled 40 patients with KRAS G12D non‑small cell lung cancer (NSCLC) who received the recommended Phase 2 dose of 1200 mg once daily. Among the 27 patients who had previously received immune‑checkpoint inhibitors and platinum chemotherapy, the confirmed objective response rate (ORR) was 52 % (95 % CI 32–71), the disease‑control rate (DCR) was 93 % (95 % CI 76–99), and median progression‑free survival (PFS) was 11.1 months (95 % CI 5.3–not estimable). The 12‑month PFS rate was 48 %. Safety findings were consistent with earlier reports, with nausea (43 %), vomiting (33 %), diarrhea (30 %) and rash (18 %) as the most common treatment‑related adverse events.
The current ORR, while slightly lower than the 61 % ORR reported at AACR 2025 among 18 patients (including unconfirmed responses), remains a strong signal of antitumor activity in a heavily pre‑treated population. The 12‑month PFS rate of 48 % aligns with the median PFS of 11.1 months, indicating durable disease control. The data build on the drug’s FDA Breakthrough Therapy designation granted in January 2026 and support the company’s plan to launch a pivotal first‑line combination study (Rasolve‑308).
Management emphasized the clinical significance of the findings. “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,” said 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, added, “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 presentation was met with enthusiasm from the scientific community. A Stifel analyst described the AACR study results as “buzzing with excitement.” The data come at a time when Revolution Medicines has recently closed a $2.2 billion public offering, underscoring investor confidence in its RAS(ON) platform and the potential of zoldonrasib to address a high‑unmet‑need market.
Strategically, the results reinforce Revolution Medicines’ broader RAS(ON) platform, which targets multiple oncogenic RAS variants. The company’s pipeline includes other G12D‑selective inhibitors, such as Astellas’ setidegrasib, and the positive Phase 1 data position zoldonrasib as a leading candidate for further development. The company plans to initiate the Rasolve‑308 pivotal study, which will evaluate zoldonrasib in combination with standard first‑line therapy for NSCLC, potentially expanding its market reach and accelerating regulatory approval.
In the competitive landscape, no approved therapies currently target KRAS G12D‑mutant NSCLC, making zoldonrasib a potentially transformative option. The data support the company’s strategy to bring a novel targeted therapy to a patient population with limited options, and the continued clinical development of zoldonrasib could reshape treatment paradigms for RAS‑driven cancers.
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