Revolution shows its selective hand

Until now Revolution Medicines has been vague about pivotal plans for its selective KRAS G12D inhibitor zoldonrasib, but the group gave more details this week at the JP Morgan healthcare meeting. In 2026 Revolution will start two phase 3 trials of the project in first-line pancreatic cancer, and one in first-line lung cancer.

One of the pancreatic cancer studies, Rasolute-305, will test zoldonrasib plus chemo, and the company also disclosed early data with this combo that look slightly better than recent results with Astellas’s KRAS G12D degrader setidegrasib.

Revolution is claiming a 63% response rate among 19 first-line PDAC patients receiving 1.2g zoldonrasib plus mFolfirinox chemo in phase 1. However, this figure includes unconfirmed responses – with 10 responses confirmed the ORR is 53%. Two additional unconfirmed responses are ongoing, and thus capable of being confirmed later.

Revolution didn’t give detailed safety data, but said adverse events were “largely consistent with mFolfirinox alone”.

At the ASCO-GI meeting last week Astellas claimed a 58% response rate with setidegrasib plus mFolfirinox – but the confirmed ORR was a less impressive 42%. Astellas is also planning to start a phase 3 study of setidegrasib plus chemo in first-line pancreatic ductal adenocarcinoma (PDAC) this year.

The second pivotal PDAC trial, Rasolute-309, will test zoldonrasib alongside Revolution’s pan-RAS inhibitor daraxonrasib – which is being tested with or without chemo in the Rasolute-303 trial. Revolution said this study had now begun, although it’s not yet listed on clinicaltrials.gov.

Lung plans

Revolution’s plans for zoldonrasib in first-line NSCLC are less clear. Here the pivotal trial will be called Rasolve-308, but the company didn’t give more details, except to say that it would look at “zoldonrasib combinations” and would start this half.

The group is also developing a selective KRAS G12C contender, elironrasib, and is promising an update on its registrational strategy for this asset later this year.

Revolution is rumoured to be a takeout target, with first AbbVie and then Merck & Co named recently as possible bidders, but nothing concrete has emerged so far. Still, with $1.9bn in cash and investments as of September, Revolution clearly has the funds to keep starting new pivotal trials.

Planned phase 3 studies of zoldonrasib

Source: company presentation.