Tango Therapeutics' New Drug Doubles Response Rates in Deadly Pancreatic Cancer Trial

Author: Benzinga Newsdesk | October 23, 2025 06:06am

Tango Therapeutics, Inc. (NASDAQ:TNGX), a clinical-stage biotechnology company committed to discovering and delivering the next generation of precision cancer medicines, today announced positive data from its ongoing Phase 1/2 study of vopimetostat (TNG462) in patients with MTAP-deleted cancers.

"Today, we are presenting a substantive dataset on our lead PRMT5 inhibitor vopimetostat, which has the potential to be a turning point for treatment of multiple difficult-to-treat MTAP-del cancers, beginning with pancreatic cancer," said Barbara Weber, M.D., President and CEO of Tango Therapeutics. "Across the 16 cancer types enrolled in the trial, the ORR is 27% in patients with a median follow-up of 9.4 months, which supports the potential for vopimetostat as the best-in-class PRMT5 inhibitor. In 2L MTAP-deleted pancreatic cancer, the median PFS is 7.2 months and the ORR is 25%, more than double that observed in historical control studies, supporting our decision to initiate a pivotal trial in this patient population in 2026. With FDA alignment on the go-forward dose of 250 mg QD, we anticipate that this study will enroll rapidly, underscoring the potential for vopimetostat to be the first MTAP-selective PRMT5 inhibitor to market."

Dr. Weber continued, "Our ongoing study of vopimetostat in combination with two Revolution Medicines (RVMD) RAS(ON) inhibitors is enrolling rapidly and we anticipate sharing safety and efficacy data from that study in 2026. Today, we also announced data from the histology-agnostic cohort of the vopimetostat phase 1/2 trial, where we observed a 49% ORR and mPFS of 9.1 months (excluding sarcoma). These data from the histology agnostic cohort demonstrate the potential of vopimetostat in multiple cancers in addition to pancreatic and lung cancer and provide further optionality for clinical development in a large patient population with high unmet need. In summary, the efficacy data we have provided, supported by a favorable tolerability profile to date, reinforce the potential for vopimetostat to be the first- and best-in-class PRMT5 inhibitor for patients with a wide range of MTAP-deleted cancer types."

"Current standard of care for patients with advanced pancreatic cancer is multi-agent chemotherapy that confers modest benefit along with side effects that can adversely affect patient quality of life," said Brian Wolpin, M.D., M.P.H., Director, Gastrointestinal Cancer Center and Hale Family Center for Pancreatic Cancer Research, Dana-Farber Cancer Institute. "These initial data support the potential of vopimetostat to meaningfully change the treatment of patients with advanced pancreatic cancer by providing more durable benefit, along with a better safety and tolerability profile, and the convenience of a once-daily pill as opposed to intravenous chemotherapy."

Efficacy Results Across Study Indications:

• As of September 1, 2025, 179 patients were enrolled across all histologies, with 154 at active doses (200 mg and above). Ninety-four tumor evaluable patients were enrolled more than 6 months prior to the efficacy analysis and included regardless of outcome. Across cancer types:
  • ORR: 27%
  • DCR: 78%
  • mPFS: 6.4 months
• 37/94 patients remained on treatment as of September 1, 2025.
  
   

Efficacy Results in Pancreatic Cancer Patients

• As of September 1, 2025, 64 patients with pancreatic cancer were enrolled. 39 of these patients received active doses and were enrolled more than 6 months prior to the analysis; in these patients:
  • ORR in 2L pancreatic cancer patients: 25%
  • ORR for all pancreatic cancer patients: 15%
  • DCR for all pancreatic cancer patients: 71%
  • mPFS in 2L patients: 7.2 months
  • mPFS in 3L+ patients: 4.1 months
• Median follow up: 7.8 months
  
   

Development Strategy in Pancreatic Cancer

• Following consultation with the FDA on the trial design scheduled later this quarter, the company plans to start a global, randomized, pivotal study in patients with MTAP-del pancreatic cancer who have received one prior line of therapy, comparing patients treated with 250 mg QD vopimetostat to patients treated with one of four standard chemotherapy regimens. The company anticipates this study will enroll approximately 300 patients and is intended to begin enrollment in 2026.
• The phase 1/2 combination study of vopimetostat with RAS(ON) multi-selective inhibitor daraxonrasib, and RAS(ON) G12D-selective inhibitor zoldonrasib (both from Revolution Medicines, RVMD), is ongoing with robust enrollment in previously treated MTAP-del/RAS mut pancreatic and lung cancer. The first dose escalation cohort of this study has been fully enrolled (n=7) and backfill is ongoing. Vopimetostat in combination with both daraxonrasib and zoldonrasib have been well-tolerated to date with exposures in the active range for each compound. The second cohort was initiated in early October. A cohort of 1L patients is expected to begin enrolling after go-forward doses have been selected. The data from this study have the potential to support a pivotal study in 1L MTAP-del/RAS mut pancreatic cancer. Initial data from the Phase 1/2 study are anticipated in 2026.

Enrollment in Lung Cancer

• As of September 1, 2025, 41 patients with 2L+ lung cancer were enrolled, 12 of whom had received active doses and were enrolled more than 6 months prior to the analysis.
• Emerging data are consistent with expectations, and the company anticipates providing a safety and efficacy update in 2026.

Efficacy Results in the Histology Agnostic Cohort:

• As of September 1, 2025, 41 patients with 13 different cancers were enrolled at active doses and had received a first dose more than 6 months prior to the analysis. This cohort excludes pancreatic and lung cancers (being evaluated in histology-specific cohorts) and sarcomas (where no activity was observed, n=0/9 responses). In this histology agnostic cohort:
  • ORR: 49%
  • DCR: 89%
  • mPFS: 9.1 months

Safety and Tolerability

Consistent with previously reported data, vopimetostat is generally well tolerated at 250 mg QD, the go-forward dose agreed with the FDA, with a potentially best-in-class safety profile. The most common treatment-related adverse events (TRAEs), predominantly grade 1, were nausea (26%), anemia (20%), fatigue (19%), dysgeusia (19%) and thrombocytopenia (13%). No treatment-related Grade 4 or 5 events occurred. Grade 3 events were rare, with the exception of anemia which was observed in 13% of patients. No drug related dose discontinuations have occurred as of September 1, 2025, and only 8% of patients treated at 250 mg QD required dose reduction to 200 mg QD.

Study Design

The Phase 1/2 study (NCT05732831) is a multicenter, open-label, first in human study in solid tumor patients whose tumor has a confirmed homozygous MTAP deletion. The first part of the study was an open-label, dose escalation and the second part is an open label dose expansion/optimization in specific MTAP-deleted tumor types. 

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