REDWOOD CITY, Calif., April 19, 2026

A major breakthrough in targeted oncology therapy has emerged as Revolution Medicines unveiled updated Phase 1 clinical data for zoldonrasib, a novel KRAS G12D-selective inhibitor, at the 2026 AACR Annual Meeting. The findings highlight encouraging efficacy and a manageable safety profile in patients with previously treated non-small cell lung cancer (NSCLC), addressing a critical unmet need in precision oncology.

Promising Clinical Outcomes in Hard-to-Treat NSCLC

The Phase 1 RMC-9805-001 trial evaluated zoldonrasib in patients with advanced solid tumors harboring the KRAS G12D mutation, one of the most challenging oncogenic drivers in cancer. Among 27 evaluable NSCLC patients, the therapy demonstrated a confirmed objective response rate of 52% and an impressive disease control rate of 93%, underscoring its potential as a transformative targeted therapy.

Patients in the study had previously received immune checkpoint inhibitors and platinum-based chemotherapy, yet showed rapid responses, with a median time to response of just 1.4 months. Notably, median progression-free survival (PFS) reached 11.1 months, while 12-month survival rates stood at 73%, signaling meaningful clinical benefit in a population with historically poor outcomes.

These results are particularly significant because KRAS G12D mutations lack approved targeted therapies, leaving clinicians reliant on conventional treatments that often deliver limited efficacy and high toxicity. The data reinforces the growing importance of precision medicine approaches in oncology.

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Safety Profile Supports Continued Development

Equally important, zoldonrasib demonstrated a manageable safety profile, consistent with earlier findings. The most common treatment-related adverse events (TRAEs) included nausea (43%), vomiting (33%), diarrhea (30%), and rash (18%), with the majority being Grade 1 in severity.

Only 13% of patients experienced Grade 3 adverse events, all of which were resolved through dose adjustments. Importantly, no Grade 4 or Grade 5 adverse events were reported, and treatment discontinuation remained low at 5%, reinforcing the drug’s tolerability.

The therapy also maintained a high mean dose intensity of 94%, indicating that patients were able to sustain treatment without significant interruptions. This balance of efficacy and tolerability positions zoldonrasib as a strong candidate for both monotherapy and combination regimens in future studies.

Advancing Targeted Therapies for RAS-Driven Cancers

Non-small cell lung cancer (NSCLC) accounts for 80–85% of all lung cancer cases, with over 229,000 new diagnoses annually in the United States alone. Despite advances in treatment, NSCLC remains a leading cause of cancer mortality due to late-stage diagnosis and limited responsiveness to traditional therapies.

The KRAS G12D mutation, present in approximately 4% of NSCLC cases and a significant proportion of other cancers, has long been considered “undruggable.” Zoldonrasib’s mechanism—a tri-complex inhibitor targeting the active RAS(ON) state via cyclophilin A binding—represents a novel therapeutic strategy aimed at directly inhibiting oncogenic signaling.

With an estimated 61,000 new KRAS G12D cancer cases annually in the U.S., the potential impact of this therapy extends far beyond lung cancer, including gastrointestinal and other solid tumors.

The company is now exploring expanded clinical development, including combination therapies with other RAS inhibitors and standard-of-care regimens, signaling a broader shift toward multi-targeted precision oncology pipelines.

The updated Phase 1 data positions zoldonrasib as a highly promising targeted therapy for patients with KRAS G12D-mutated NSCLC, offering both strong clinical activity and a favorable safety profile. As development progresses, this therapy could redefine treatment paradigms for RAS-driven cancers, marking a significant step forward in the evolution of precision oncology and next-generation targeted therapeutics.

Source: Revolution Medicines press release