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Revolution Medicines breaks ground in challenging pancreatic cancer with two RAS drugs

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In an interview Friday, Revolution Medicines CEO Mark Goldsmith, who says he prefers to understate rather than exaggerate, floated a lofty goal: cure pancreatic cancer — or get close.

“That’s our aim, and we don’t think that’s right around the corner, but we’re off to a very good start,” he told Endpoints News. It’s an ambitious vision, given that the five-year survival rate for pancreatic cancer is 13%, according to the American Cancer Society.

Revolution is developing a suite of RAS inhibitors, and the company’s shares have more than doubled in the past 12 months because of excitement over their potential to treat solid tumors, particularly pancreatic cancer. The Redwood City, CA-based company reported results this week from early-stage trials of two of its experimental treatments in pancreatic cancer, where more than 90% of cases harbor RAS mutations.

In a late-breaking presentation Friday, Revolution Medicines said that 12 of 40 previously treated pancreatic cancer patients who received a 1,200 mg daily dose of its KRAS G12D inhibitor, called RMC-9805, saw their tumors shrink at least 30%. (The company included confirmed responses as well as unconfirmed responses still on treatment.)

That’s good for a 30% response rate, and the company said it would use a 1,200 mg dose in a Phase 2 trial for pancreatic cancer.

The data, presented at what’s known as the Triple Meeting, were the first clinical results from RMC-9805. They’re from a broader Phase 1/1b study looking at the drug in patients with solid tumors harboring KRAS G12D mutations who had received a median of two previous treatments.

The company, which informally goes by RevMed, said that 179 patients have been dosed with the drug. At the 1,200 mg daily dose, with which 99 patients have been treated, the most common side effects were nausea, diarrhea and vomiting and rash. It described those adverse events as low-grade and limited, though there was one grade 3 case of elevated liver enzymes.

More than one mutation

The company also has a multi-RAS inhibitor that can tackle a range of mutations in a Phase 3 trial. Known as RMC-6236, RevMed announced it dosed a first pancreatic cancer patient in that trial on Monday. The study will include a core population of pancreatic cancer patients with RAS G12X mutations, as well as other mutations.

RevMed shared updated results from 127 patients in an earlier Phase 1/1b study of RMC-6236. In that study, overall survival rates were 14.5 months in both previously treated pancreatic cancer patients with any RAS mutation, as well as with those with a mutation at codon 12 (which is referred to as KRAS G12X).

While the study didn’t have a control arm, Jefferies analyst Kelly Shi said the benchmark for survival in those patients with chemotherapy is about six to seven months.

Grade 3 or greater side effects related to the drug were rash (which impacted 8% of patients), stomatitis and diarrhea, and 35% of patients required dose modifications because of side effects, but none dropped out because of that.

Goldsmith said the two experimental compounds have “overlapping but also distinct profiles, and two overlapping but also distinct ranges of target.”


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