Tango Therapeutics has reported an 82% objective response rate with vopimetostat and daraxonrasib in previously treated pancreatic cancer, prompting plans for a Phase 3 trial in 2027.

Response rates and progression-free survival

Updated Phase 1/2 trial results from Tango Therapeutics show an 82% objective response rate (ORR) among 22 evaluable patients with previously treated, metastatic pancreatic ductal adenocarcinoma (PDAC) carrying both MTAP deletion and RAS mutations.

The patients received vopimetostat, an investigational PRMT5 inhibitor, in combination with daraxonrasib, a RAS(ON) inhibitor developed by Revolution Medicines. The results were based on data collected up to 20 August 2026, with a median follow-up of 7.1 months.

The combination achieved a median progression-free survival (PFS) that had not yet been reached, while the nine-month PFS rate was 88%. All 22 evaluable patients achieved disease control, defined as a complete or partial response or stable disease.

Of the 22 patients, 13 received the combination as third-line treatment, meaning they had already undergone two previous lines of therapy. The remaining patients received it as second-line treatment.

The reported 82% response rate comprised 18 patients, including 11 confirmed partial responses and seven initially unconfirmed partial responses. Tango said all seven unconfirmed responses were subsequently confirmed after the data cutoff.

The findings come from an ongoing, open-label Phase 1/2 dose-escalation and expansion study. The trial is investigating vopimetostat in combination with either daraxonrasib or zoldonrasib in patients with RAS-mutant, MTAP-deleted pancreatic cancer or non-small cell lung cancer (NSCLC).

The study is not a randomised comparison against standard treatment, so the results cannot establish whether the combination is more effective than existing therapies.

Safety findings and treatment-related adverse events

At the lower dose level, the combination was generally well tolerated among 25 safety-evaluable patients with pancreatic cancer.

There were no dose-limiting toxicities or withdrawals due to treatment-related adverse events at this dose level. Five patients (20%) required a dose reduction, while 10 (40%) experienced Grade 3 treatment-related adverse events. No Grade 4 or Grade 5 treatment-related adverse events were reported.

The most common treatment-related adverse events were stomatitis, affecting 48% of patients; rash, affecting 44%; and diarrhoea, affecting 28%. These events were all Grade 1 or Grade 2.

The higher dose level was less well tolerated, with three dose-limiting toxicities reported in two patients among the four safety-evaluable patients.

Tango also reported results from five patients with NSCLC treated at dose level 1. The objective response rate in this group was 80%, with all five patients achieving disease control. However, this small sample is insufficient to draw firm conclusions about efficacy in lung cancer.

Tango plans Phase 3 trial for 2027

Following discussions with the US Food and Drug Administration (FDA), Tango plans to initiate a global, randomised Phase 3 trial in the first half of 2027. The study will evaluate vopimetostat plus daraxonrasib as a first-line treatment for patients with MTAP-deleted pancreatic cancer.

The planned trial will randomise patients in a 1:1 ratio to receive either the drug combination or standard-of-care chemotherapy. The dual primary endpoints will be objective response rate and progression-free survival, with overall survival as a key secondary endpoint.

Tango also intends to discuss the possibility of seeking regulatory approval for the combination in second-line pancreatic cancer.

Malte Peters, CEO and president of Tango Therapeutics, said: “It is encouraging to see that the clinical activity and tolerability observed in our initial June 2026 dataset has been confirmed with longer follow-up and in a larger patient population, affirming our belief that the response rate and durability observed with vopimetostat plus daraxonrasib surpass any published PDAC datasets, even in front-line settings.”

Alexander Spira, co-director of the Virginia Cancer Specialists Research Institute and a principal investigator of the study, said: “In this updated analysis, the large majority of patients remained progression-free at nine months despite being heavily pretreated, with more than half receiving the combination as third-line therapy.”

The next stage of development will determine whether the encouraging early results can be reproduced in a larger, randomised study and whether the combination offers a meaningful clinical benefit over standard chemotherapy.

Tango is also evaluating vopimetostat with zoldonrasib, another RAS(ON) inhibitor, in pancreatic cancer patients with MTAP deletion and a KRAS G12D mutation. In that separate combination arm, the company reported a 54% objective response rate among 35 evaluable patients and a nine-month PFS rate of 61%.

These findings represent a separate treatment combination and should not be conflated with the vopimetostat and daraxonrasib results.