Jefferies analyst Kelly Shi in a Sunday note to investors said that both data drops for Revolution Medicines’ experimental RAS inhibitors are positive and could be “synergistic” in the first-line setting for pancreatic ductal adenocarcinoma.
Revolution Medicines on Friday posted a pair of readouts for its investigational RAS inhibitors, demonstrating strong survival outcomes and response rates in patients with advanced pancreatic ductal adenocarcinoma.
According to a company presentation on Friday, these data will help advance its mission “to revolutionize patients with RAS-addicted cancers,” leading to better treatment outcomes in pancreatic ductal adenocarcinoma (PDAC), a highly aggressive and lethal type of pancreatic cancer. According to Revolution, more than 90% of PDAC tumors carry oncogenic RAS mutations.
In a Friday late-breaking oral session at the 2024 Symposium on Molecular Targets and Cancer Therapeutics of the EORTC-NCI-AACR, Revolution revealed Phase I/Ib data for RMC-9805, an orally available RAS(ON) G12D-selective inhibitor. The biotech touted strong preliminary efficacy for RMC-9805, which elicited a 30% objective response rate and an 80% disease control rate.
Revolution combined both confirmed and pending treatment responses in its outcome assessment.
RMC-9805 also had an “encouraging safety profile,” the company said in its announcement. In the 99 patients who were treated with 1,200 mg of RMC-9805 daily, the most common treatment-related toxicities were gastrointestinal in nature, including nausea and diarrhea. There were no grade 4 or 5 adverse events, though four patients needed to have their doses lowered due to side effects.
Revolution CEO Mark Goldsmith in a statement said that the company is “pleased” with these early data for RMC-9805, “which demonstrate encouraging initial safety, tolerability and antitumor activity.” These findings suggest that the candidate “has the potential to play a role in an emerging treatment paradigm” for PDAC patients, and further provide compelling evidence of Revolution’s approach to target RAS(ON) in RAS-addicted cancers.
Also last week, the biotech revealed more data to back its RAS(ON) pipeline, announcing that its Phase I/Ib RMC-6236 showed “durable antitumor activity” in advanced PDAC patients, resulting in “encouraging” progression-free and overall survival outcomes.
Unlike RMC-9805, RMC-6236 is a RAS(ON) multi-selective inhibitor. The study results— which were also presented at the EORTC-NCI-AACR meeting—primarily enrolled patients with KRAS G12X mutations, in whom RMC-6236 had landmark overall survival of 89% at six months. Objective response rate was 29%.
RMC-6236 was generally well-tolerated at the tested dose levels of 160 mg to 300 mg, once-daily. The most common adverse events grade 3 and above were rashes, stomatitis and diarrhea. Toxicities necessitating dose adjustment were reported in 35% of patients.
In a Sunday investor note, Jefferies analyst Kelly Shi said that both readouts “are straightforwardly positive” for Revolution and called both RMC-9806 and RMCM-6236 “promising assets” that could be “synergistic” in the first-line setting for PDAC.
Both molecules have “complementary” mechanisms of action, Shi said, and Revolution is “committed” to studying the combo in first-line PDAC, though it has yet to reveal specific details for this program.
