Encouraging data for combination regimens of Revolution Medicines’ zoldonrasib “reinforce the path to leadership in PDAC” for the biotech, according to Truist Securities.
Revolution Medicines’ second RAS inhibitor elicited encouraging response rates in a Phase 1/2 study of pancreatic cancer, further strengthening the biotech’s leadership position in this disease.
Revolution’s lead asset, daraxonrasib, made waves in April when the company announced that it doubled overall survival versus chemotherapy in a Phase 3 trial of patients with pancreatic cancer. Revolution is also working on another candidate, zoldonrasib, that is specifically designed to target the G12D mutation in RAS. According to the biotech’s website, this mutation is “the most common driver of RAS-addicted cancers.”
Phase 1/2 data, to be presented next week at the ESMO Gastrointestinal Cancers Congress in Munich, seem to support this mechanism. Zoldonrasib, used as a frontline treatment alongside the standard chemo regimen mFOLFIRINOX, elicited an overall response rate (ORR) of 82% in patients with metastatic pancreatic ductal adenocarcinoma (PDAC) who carry the RAS-G12D mutation.
This outcome “compares favorably with chemo alone,” Truist Securities analysts told investors in a note late Wednesday, adding that in this patient population and treatment setting, chemotherapy results in an ORR of around 30% to 40%.
Revolution earlier this week launched the Phase 3 RASolute 305 study, testing zoldonrasib plus mFOLFIRINOX as a frontline PDAC treatment. The study has a primary completion date in December 2028, according to a federal clinical trials database.
If successful, this zoldonrasib combo “could provide an additional treatment option – and potentially a more active regimen” for patients with KRAS G12D-mutated PDAC who are otherwise unable to tolerate the side effects of more intensive regimens, Truist said. Revolution’s Phase 1/2 data for zoldonrasib showed a “manageable” safety profile, with side effects consistent with known chemotherapy toxicities, per the abstract.
Also at ESMO GI, Revolution will present second-line data for a combination regimen of zoldonrasib and daraxonrasib, which elicited a 50% ORR in patients with metastatic PDAC.
Taken together, these zoldonrasib combination regimens “reinforce the path to leadership in PDAC” for Revolution, Truist said Wednesday.
Following daraxonrasib’s blowout performance in April, Truist has grown extra bullish about Revolution, calling the biotech “the next oncology titan” in a May 18 note. Revolution, the firm said at the time, “is evolving into a major revenue-generating oncology company, with daraxonrasib (“daraxon”) emerging as one of the most important drugs in PDAC and broader RAS-mutant cancers this decade.”
Oncology powerhouse Merck had its eye on Revolution even before the daraxonrasib readout. The pharma was reportedly courting Revolution in January, though talks fell apart not long after. The Financial Times reported earlier this month that exiting via an acquisition is “not an area of high priority” for the biotech, according to CEO Mark Goldsmith.
