Revolution Medicines tackles pancreatic cancer with two RAS drugs

In a recent interview, Revolution Medicines CEO Mark Goldsmith revealed an ambitious objective: to potentially cure pancreatic cancer. Despite the daunting nature of this goal, given the current five-year survival rate of only 13% as reported by the American Cancer Society, Goldsmith believes that the company is making significant strides towards this aim.

Revolution Medicines, headquartered in Redwood City, CA, is focusing on developing a series of RAS inhibitors. This effort has sparked considerable interest, leading to the company’s stock more than doubling over the past year. The excitement largely stems from the promising potential of these inhibitors to treat solid tumors, with pancreatic cancer being a primary target. The company recently shared results from early-stage trials for two of their experimental treatments targeting pancreatic cancer, a disease in which over 90% of cases involve RAS mutations.

In an important presentation last Friday, Revolution Medicines disclosed findings from its early-stage trials. Out of 40 pancreatic cancer patients who had previously undergone treatment and were given a daily dose of 1,200 mg of the KRAS G12D inhibitor, known as RMC-9805, 12 patients experienced a reduction in tumor size by at least 30%. The company reported these findings as a combination of confirmed and unconfirmed responses still under treatment, resulting in a 30% response rate. Based on these outcomes, the company plans to proceed with the 1,200 mg dose in a Phase 2 trial for pancreatic cancer.

These results represent the first clinical data from RMC-9805, which is part of a broader Phase 1/1b study evaluating the drug in patients with solid tumors harboring KRAS G12D mutations. These patients had previously undergone a median of two treatments. In total, 179 patients have received doses of RMC-9805, with 99 patients being treated at the 1,200 mg daily dose. Common side effects noted at this dosage included nausea, diarrhea, vomiting, and rash, which were generally low-grade. However, there was one instance of grade 3 elevated liver enzymes.

In addition to RMC-9805, Revolution Medicines is also advancing a multi-RAS inhibitor, RMC-6236, capable of addressing a variety of mutations. This compound has recently entered a Phase 3 trial, with the first pancreatic cancer patient dosed earlier this week. The trial's core population will include pancreatic cancer patients with RAS G12X mutations, among other mutations.

Updated data from an earlier Phase 1/1b study of RMC-6236 involving 127 patients showed an overall survival rate of 14.5 months for previously treated pancreatic cancer patients with any RAS mutation. This included those with mutations at codon 12, known as KRAS G12X. Analyst Kelly Shi from Jefferies noted that the benchmark survival rate with chemotherapy for these patients is around six to seven months, indicating a significant improvement with RMC-6236.

The main side effects of RMC-6236 reported were grade 3 or higher rash, stomatitis, and diarrhea. Approximately 35% of patients required dose adjustments due to side effects, although no patients discontinued treatment because of these adverse reactions.

Goldsmith highlighted that while the two experimental compounds, RMC-9805 and RMC-6236, have overlapping but distinct profiles and target ranges, they both show promise in the fight against pancreatic cancer. The company's ongoing advancements in this area offer hope for better treatment options and improved survival rates for patients battling this challenging disease.