Tango Therapeutics Vopimetostat Results Spur Phase 3

Tango Therapeutics disclosed on June 8 that its PRMT5 inhibitor vopimetostat showed unusually strong early activity in metastatic pancreatic cancer, prompting plans to advance the combination toward late-stage testing with trial design work scheduled for the second half of 2026.

Tango Therapeutics, Inc. (TNGX) is a clinical-stage precision oncology company developing vopimetostat (TNG908), an oral MTA-cooperative PRMT5 inhibitor targeting MTAP-deleted tumors. The company is testing vopimetostat in a Phase 1/2 dose-escalation and expansion study, combining it with RAS(ON) inhibitors from Revolution Medicines.

PDAC Trial Results

In the daraxonrasib arm of the Phase 1/2 study, 20 patients with metastatic pancreatic ductal adenocarcinoma (PDAC) were enrolled as of the May 28, 2026, data cutoff. Twelve patients were response-evaluable with at least 14 weeks of follow-up, and 11 of those achieved an objective response, a 92.0% objective response rate (ORR), with nine responses confirmed. The disease-control rate was 100%, and the six-month progression-free survival (PFS) rate was 90%, with median PFS not reached at analysis.

The PDAC cohort was heavily pretreated; about half received the combination as third-line therapy, and roughly 70% had liver metastases. In a small non-small-cell lung cancer (NSCLC) cohort, all three evaluable patients responded, though the sample size was too small for firm conclusions.

Across 27 patients treated with vopimetostat plus Revolution’s zoldonrasib—primarily PDAC and NSCLC—the combination produced a 52.0% ORR, a six-month PFS rate of 74.0%, and a disease-control rate of 96.0%.

Safety, Dosing, and Phase 3 Development

Tango reported that vopimetostat combinations with daraxonrasib or zoldonrasib were generally well tolerated with no new safety signals. Most treatment-related adverse events were Grade 1 or 2, commonly rash, stomatitis or mucositis, and diarrhea. There were no Grade 4 or 5 treatment-related events and no discontinuations due to adverse events.

Dosing in the daraxonrasib arm involved vopimetostat at 200 mg or 250 mg once daily plus daraxonrasib 100 mg once daily. Three dose-limiting toxicities occurred in two patients at the 250 mg vopimetostat dose, including Grade 3 rash and Grade 3 stomatitis with fatigue, prompting closer dose evaluation.

The company said the data support rapid advancement of the vopimetostat plus daraxonrasib combination into a randomized Phase 3 trial in first-line MTAP-deleted pancreatic cancer. Tango’s June 2026 corporate presentation also lists orphan drug designation for pancreatic cancer in the U.S. and EU. Vopimetostat and the Revolution RAS(ON) inhibitors remain investigational agents. The company expects to finalize Phase 3 trial design in the second half of 2026.