New KRAS Drug Zoldonrasib Shows 52% Response Rate in Hard-to-Treat Lung Cancer

KRAS mutations are among the most common cancer-driving genetic changes, yet for decades they were considered nearly impossible to target with drugs. While two KRAS inhibitors have been approved for a related mutation (G12C), patients with KRAS G12D mutations — found in roughly 4-5% of non-small cell lung cancer cases — have had no targeted options. Zoldonrasib is designed specifically to address this gap.

In a phase I trial reported at the American Association for Cancer Research annual meeting, zoldonrasib achieved an objective response rate of 52% and a disease control rate of 93% in patients previously treated with chemotherapy and immunotherapy. Median progression-free survival reached 11.1 months, with 73% of patients alive at 12 months — outcomes that dramatically outperform the current docetaxel-based standard of care.

The drug was well tolerated at the recommended phase II dose of 1,200 mg daily. Most side effects were mild gastrointestinal issues. Only 13% of patients experienced grade 3 adverse events, and no grade 4 or higher events were observed. Dose discontinuations occurred in just 5% of patients, underscoring its tolerability profile.

Zoldonrasib works by covalently binding to the active, GTP-bound state of the KRAS G12D protein, locking it in a way that blocks the uncontrolled cell signaling that drives tumor growth. The FDA has granted it breakthrough therapy designation, accelerating its path toward potential approval.

While these results are promising, this remains a phase I study with a relatively small patient population. Larger randomized trials are needed to confirm efficacy and long-term survival benefits. Still, for a patient population with very limited options, these early findings represent a meaningful step forward in precision oncology.