Tango Therapeutics plans pivotal vopimetostat trial in second-line pancreatic cancer

Tango Therapeutics said it remains on track to launch a pivotal 300-patient randomized trial of vopimetostat in second-line pancreatic cancer this year after interactions with the U.S. Food and Drug Administration late last year. The company said the trial has a hierarchical endpoint structure that evaluates progression-free survival first and then overall survival, and that the study will be randomized against chemotherapy in the second-line setting.

The company said it shared the trial design, statistical analysis plan, thinking around dose selection, and sample size calculations with the FDA and received what it characterized as significant support from the agency. It said the study has a global footprint spanning the U.S., Europe, and Asia-Pacific, which it believes supports rapid enrollment.

Tango said it has now achieved clinical proof of concept for vopimetostat and is seeking regulatory approval either as monotherapy or potentially in combination with a RAS inhibitor. It plans to provide an updated monotherapy data set later this year, though the exact timing has not been decided, and said an update could potentially coincide with presentation of combination data.

The company is also evaluating vopimetostat in combination with Revolution Medicines' RAS inhibitors, including the pan-RAS inhibitor daraxonrasib and the KRAS G12D-selective inhibitor zoldonrasib. It said the program was driven by preclinical findings in which the two companies observed synergy when combining the agents.

The first patient in the combination study was enrolled in June of last year. As of the discussion, the study had enrolled 14 patients in the daraxonrasib arm and 16 patients in the zoldonrasib arm, and the company said data remain immature.

On dose selection, the company said it is oriented around a benchmark for RAS inhibitor monotherapy in second-line pancreatic cancer of around 29% to 30% depending on the compound, and expects or hopes to perform significantly better in combination. It said the current data set is not yet sufficient to make conclusions and that duration of response and progression-free survival are important measures because both RAS inhibition and PRMT5 inhibition may require time on treatment for patients to benefit.

The combination study is also open to non-small cell lung cancer, though enrollment progress has been greater in pancreatic cancer. The company said its pipeline also includes TNG456 in dose escalation in glioblastoma and non-small cell lung cancer cohorts, as well as a tumor-agnostic MTAP-deleted cohort, with multiple data updates anticipated later this year.