Revolution Medicines Receives FDA Breakthrough Therapy Designation For Zoldonrasib, Advancing Targeted Cancer Treatment

Revolution Medicines, Inc., a late-stage clinical oncology company focused on developing targeted therapies for RAS-addicted cancers, announced that the U.S. Food and Drug Administration (FDA) has granted Breakthrough Therapy Designation to zoldonrasib. This investigational RAS(ON) G12D-selective inhibitor is intended for adults with KRAS G12D-mutated locally advanced or metastatic non–small cell lung cancer (NSCLC) who have previously been treated with anti-PD-1/PD-L1 therapy and platinum-based chemotherapy.

The FDA’s decision is supported by data from the monotherapy cohort of the Phase 1 RMC-9805-001 clinical trial, which is evaluating zoldonrasib in patients with advanced KRAS G12D solid tumors. Early results from this cohort have shown a strong clinical profile, including promising antitumor activity and a safety and tolerability profile that supports continued development.

According to Mark A. Goldsmith, M.D., Ph.D., chief executive officer and chairman of Revolution Medicines, the Breakthrough Therapy Designation represents an important milestone for the company. He noted that this is the first time the FDA has granted such a designation for an investigational therapy specifically designed to target the RAS G12D mutation. 

He explained that patients with KRAS G12D cancers currently do not have any approved targeted treatment options, making this recognition especially significant. Goldsmith added that this designation builds on the momentum created by the company’s earlier achievements with daraxonrasib, a RAS(ON) multi-selective inhibitor, and elironrasib, a G12C-selective inhibitor, reinforcing the potential of their growing pipeline of RAS(ON) inhibitors.

Zoldonrasib is an innovative tri-complex inhibitor that functions by binding to cyclophilin A and forming a complex that selectively identifies and inhibits the active, oncogenic RAS G12D(ON) mutant. Revolution Medicines is studying zoldonrasib both as a monotherapy and in combination regimens across multiple cancer types, stages, and treatment settings.

Breakthrough Therapy Designation is intended to accelerate the development and review of therapies that address serious or life-threatening conditions where significant unmet needs remain. To qualify, a therapy must show encouraging preliminary clinical evidence indicating substantial improvement over currently available treatment options.