Tango's vopimetostat plus Rasonque shrinks tumours in 82% of MTAP-deleted pancreatic cancers

Tango Therapeutics reported at the ESMO congress in Madrid on 23 October 2026 that its PRMT5 inhibitor vopimetostat, given with Revolution Medicines' RAS(on) inhibitor Rasonque (daraxonrasib), produced tumour responses in 82% of evaluable patients with MTAP-deleted, RAS-mutant metastatic pancreatic cancer ¹². The regimen is oral and contains no chemotherapy ².

What the trial found

The data come from an ongoing phase 1/2 study. In 22 evaluable patients treated in the second or third line, the objective response rate was 82% ¹. At nine months, 88% of patients were alive without their cancer progressing, and median progression-free survival had not yet been reached ¹². More than half of these patients received the combination as third-line therapy, according to lead investigator Alexander Spira of Virginia Cancer Specialists Research Institute ¹.

A smaller cohort of five evaluable patients with non-small cell lung cancer showed an 80% response rate and a 100% disease control rate ¹.

Dose matters. Across 30 patients with pancreatic or lung cancer on the 200 mg once-daily dose, Tango described the combination as “generally well-tolerated”, while it said the 250 mg dose “was not well-tolerated” ¹. Tango shares fell by around 9% on the day, a move pharmaphorum linked either to the safety findings or to profit-taking after earlier gains ¹.

The biological rationale is specific. Between 18% and 40% of pancreatic cancers carry mutations or deletions in the MTAP gene, which causes a metabolite called MTA to build up and partly suppress PRMT5 ¹. Adding vopimetostat is intended to push PRMT5 activity in tumour cells below the level they need to survive, while normal cells keep their usual activity ¹. Pairing this with RAS(on) blockade is also meant to limit the tumour resistance that has been seen when Rasonque is used alone ¹.

Spira said the durability was achieved with “an oral, chemotherapy-free regimen” and argued that a vopimetostat combination has the potential “to redefine the standard of care in a disease that has been notoriously difficult to treat” ¹.

What it means for the market

The result strengthens the case that pancreatic cancer patients gain more from combining targeted drugs than from single agents, a shift away from chemotherapy as the backbone of treatment ². It also extends the commercial reach of Rasonque, whose RASolute 302 monotherapy trial drew a standing ovation at ASCO earlier this year ¹. For Revolution Medicines, a partner drug that lifts efficacy in a defined biomarker group could widen use of Rasonque; for Tango, the value of vopimetostat now rests on a biomarker-selected population.

Tango is preparing a registrational phase 3 trial of vopimetostat at 200 mg plus Rasonque as a front-line treatment for MTAP-deleted pancreatic cancer ¹. It also plans to discuss with regulators whether the phase 1/2 data could support approval in the second-line setting ¹. Oncology teams with RAS or PRMT5 programmes will watch how regulators respond, since an approval on single-arm data would set the bar for competing combinations.

Caveats

The efficacy figures rest on 22 pancreatic cancer patients in an early, non-randomised study, and the lung cancer cohort has only five ¹. The higher dose was poorly tolerated, so the 200 mg dose carries the programme forward ¹. Median progression-free survival is not yet known ¹. Tango aims to start the front-line phase 3 trial in the first half of 2027 ¹.