On April 27, 2025 Zoldonrasib, a RAS(ON) G12D-selective inhibitor, demonstrated acceptable tolerability and encouraging initial antitumor activity in patients with previously treated KRAS G12D mutant non-small cell lung cancer
REDWOOD CITY, Calif., April 27, 2025 (GLOBE NEWSWIRE) — Revolution Medicines, Inc. (Nasdaq: RVMD), a late-stage clinical oncology company developing targeted therapies for patients with RAS-addicted cancers, reported new clinical data for zoldonrasib (RMC-9805), a RAS(ON) G12D-selective inhibitor, as monotherapy in patients with KRAS G12D mutant non-small cell lung cancer (NSCLC) (Press release, Revolution Medicines, APR 27, 2025, View Source [SID1234652192]). Results were highlighted in the official press program at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting in Chicago, Illinois, and will be featured in a late-breaking oral presentation on April 27, 2025, at 5:00 p.m. Central Time.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

"We are pleased to share new clinical data for zoldonrasib, our innovative, oral RAS(ON) G12D-selective inhibitor, which demonstrates acceptable safety and tolerability and encouraging initial antitumor activity in patients with non-small cell lung cancer. These data reinforce the clinical potential of zoldonrasib following the initial tolerability and antitumor activity reported late last year in patients with pancreatic ductal adenocarcinoma," said Mark A. Goldsmith, M.D., Ph.D., chief executive officer and chairman of Revolution Medicines. "Together these results support further evaluation of zoldonrasib as monotherapy and in combination as we continue efforts to advance innovative targeted medicines for patients living with these hard-to-treat cancers."

RMC-9805-001 is a multicenter, open-label, dose escalation and dose-expansion Phase 1 study designed to evaluate zoldonrasib in patients with advanced solid tumors harboring a KRAS G12D mutation.

As of a December 2, 2024 data cutoff date, 90 solid tumor patients were treated with 1200 mg once daily (QD), the candidate recommended Phase 2 dose. In these patients, zoldonrasib demonstrated an acceptable safety profile, that was generally consistent with previously reported data for this compound in pancreatic cancer, and was generally well tolerated. The most common treatment-related adverse events (TRAEs) occurring in at least 10% of patients were nausea (39%), diarrhea (24%), vomiting (18%), and rash (12%). TRAEs were primarily Grade 1 or 2 in severity, with two patients (2%) experiencing Grade 3 events that resolved following dose interruption. Zoldonrasib had a favorable mean dose intensity of 98% and no dose limiting toxicities were observed.

Preliminary antitumor activity was assessed in 18 efficacy-evaluable patients with NSCLC at the 1200 mg QD dose. The objective response rate (confirmed or pending confirmation) was 61% (n=11) and the disease control rate was 89% (n=16).

"There is a high unmet need for new treatments within this patient population as there are currently no targeted therapies approved for any RAS G12D mutant cancer," said Kathryn Arbour, M.D., thoracic medical oncologist at Memorial Sloan Kettering Cancer Center and principal investigator and lead author for the RMC-9805-001 presentation. "While the data are from an early, small subset of patients, it is encouraging to see this level of tolerability and antitumor activity in patients with NSCLC carrying this RAS mutation."