RMC-5127 / Revolution Medicines - LARVOL DELTA

Discovery of RMC-5127, an oral, RAS (ON) G12V-selective, noncovalent, tri-complex inhibitor (AACR 2025) - "Across a panel of preclinical PDAC and NSCLC models harboring KRAS G12V, RMC-5127 monotherapy induced tumor regressions in the majority of models and was well-tolerated. In addition, dose-dependent exposure of RMC-5127 was observed in the whole brain of naïve mice, indicating the compound is brain penetrant, and RMC-5127 exhibited profound antitumor activity in relevant intracranial KRAS G12V mutant tumor xenograft models, with regressions observed at well-tolerated doses."

Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • KRAS

Revolution Medicines to Deliver Multiple Presentations at the 2025 American Association for Cancer Research (AACR) Annual Meeting (GlobeNewswire) - "Revolution Medicines...announced 11 oral and poster presentations will be featured at the American Association for Cancer Research (AACR) Annual Meeting....The first clinical data in non-small cell lung cancer from the Phase 1 study of zoldonrasib, a RAS(ON) G12D-selective inhibitor, will be featured in a late breaking oral presentation."

Clinical data • Late-breaking abstract • Preclinical • Cholangiocarcinoma • Colorectal Cancer • Non Small Cell Lung Cancer • Pancreatic Ductal Adenocarcinoma

Revolution Medicines Reports Fourth Quarter and Full Year 2024 Financial Results and Update on Corporate Progress (GlobeNewswire) - "Strategic Priorities and Markers of Progress:...(i) The company expects to share additional clinical safety and antitumor activity on zoldonrasib in the second quarter of 2025. The company currently expects to initiate one or more pivotal combination trials in 2026 that incorporate either elironrasib or zoldonrasib and expects to share clinical data supporting these plans in the second or third quarter of 2025; (ii) The company expects to advance RMC-5127, a RAS(ON) G12V-selective inhibitor, to a clinic-ready stage in 2025 to enable the expected initiation of a first-in-human dose escalation Phase 1 clinical trial in 2026."

Clinical data • New trial • Solid Tumor

RMC-5127, a first-in-class, orally bioavailable mutant-selective RASG12V(ON) inhibitor is central nervous system (CNS)-penetrant and demonstrates anti-tumor activity in a preclinical intracranial xenograft model (AACR 2024) - "The anti-tumor activity of RMC-5127 in intracranial tumors was consistent with that in subcutaneous tumors at equivalent tumor exposures. In conclusion, these preclinical data demonstrate that RMC-5127 is a CNS-penetrant RASG12V(ON) inhibitor and support further study to determine the potential to benefit patients with advanced RASG12V-mutated cancers, including those that have developed or are at risk of developing brain metastases."

Preclinical • Brain Cancer • CNS Tumor • Colorectal Cancer • Gastrointestinal Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Pancreatic Cancer • Solid Tumor • HRAS • KRAS

Revolution Medicines to Deliver Multiple Presentations at the Upcoming American Association for Cancer Research Annual Meeting 2024 (GlobeNewswire) - "Revolution Medicines...announced the company will deliver multiple presentations at the upcoming American Association for Cancer Research (AACR) Annual Meeting 2024 being held April 5-10, 2024, in San Diego, California."

Preclinical • Non Small Cell Lung Cancer • Pancreatic Ductal Adenocarcinoma