As of September 1, 2025, the trial had enrolled 179 patients across histologies, 154 of whom were treated with active doses of vopimetostat (defined as 200 mg and above). Among 94 tumor-evaluable patients across cancer types who were enrolled more than 6 months before the efficacy analysis, the overall response rate (ORR) was 27%, the disease control rate (DCR) was 78%, and the median progression-free survival (PFS) was 6.4 months. In total, 37 patients remained on treatment.
Among 64 patients with pancreatic cancer who were enrolled, 39 received active doses of the agent and were enrolled more than 6 months before the efficacy analysis. The median follow-up in this cohort was 7.8 months. In second-line patients with pancreatic cancer, the ORR was 25%, and the median PFS was 7.2 months. In all pancreatic cancer patients, the ORR was 15%, and the DCR was 71%. Among patients with pancreatic cancer who received vopimetostat in the third-line setting and beyond, the median PFS was 4.1 months.
“[The] current standard of care for patients with advanced pancreatic cancer is multi-agent chemotherapy that confers modest benefit along with adverse effects [AEs] that can adversely affect patient quality of life,” Brian Wolpin, MD, MPH, director of the Gastrointestinal Cancer Center and the Hale Family Center for Pancreatic Cancer Research at Dana-Farber Cancer Institute in Boston, Massachusetts, stated in a news release. “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.”
Additionally, as of September 1, 2025, the trial had enrolled 41 patients with second-line or later lung cancer, 12 of whom received active doses of the agent and were enrolled more than 6 months before this analysis. Data emerging from this cohort are consistent with efficacy expectations, according to the news release.
“Today, we are presenting a substantive dataset on our lead PRMT5 inhibitor vopimetostat, which has the potential to be a turning point for [management] of multiple difficult-to-treat MTAP-deleted cancers, beginning with pancreatic cancer,” Barbara Weber, MD, president and chief executive officer of Tango Therapeutics—the developer of vopimetostat—added in the news release. “Across the 16 cancer types enrolled in the trial, the ORR…supports the potential for vopimetostat as the best-in-class PRMT5 inhibitor. In [second-line] 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 [once daily], we anticipate that this study will enroll rapidly, underscoring the potential for vopimetostat to be the first MTAP-selective PRMT5 inhibitor to market.”
Moreover, the trial enrolled 41 patients with 13 different cancers (excluding pancreatic cancers, lung cancers, and sarcomas) to a histology-agnostic cohort. These patients received active doses of vopimetostat and had received their first dose of the agent more than 6 months before the analysis. In this cohort, the ORR was 49%, the DCR was 89%, and the median PFS was 9.1 months.
“The 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,” Weber continued in the news release. “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.”
What is the design of the phase 1/2 study of vopimetostat in solid tumors?
This multicenter, open-label, first-in-human trial is enrolling patients with solid tumors with a confirmed homozygous MTAP deletion. Part 1 of the study was an open-label, dose-escalation portion. Part 2 is an open-label dose-escalation/optimization portion among patients with specific MTAP-deleted tumor types. Patients needed to be at least 18 years of age; have an ECOG performance status of 0 or 1; have confirmed locally advanced, metastatic, and/or unresectable solid tumors; and have adequate organ, liver, and renal function.2
In part 2, the primary end point is anti-neoplastic activity. Secondary end points in part 2 include AEs and pharmacokinetics.
What is the safety profile of vopimetostat?
The news release noted that vopimetostat was generally well tolerated at the go-forward dose (250 mg daily) and has a potentially best-in-class safety profile.1 The most commonly reported treatment-related AEs (TRAEs) were nausea (26%), anemia (20%), fatigue (19%), dysgeusia (19%), and thrombocytopenia (13%); these were predominantly grade 1. No grade 4 or 5 TRAEs were observed. Although grade 3 AEs were rare, grade 3 anemia was reported in 13% of patients. As of September 1, 2025, no patients required drug-related dose discontinuations, and 8% of patients treated at the go-forward dose required dose reduction to 200 mg daily.
What are the next steps for evaluating vopimetostat in pancreatic cancer?
“Our ongoing study of vopimetostat in combination with 2 Revolution Medicines RAS(ON) inhibitors is enrolling rapidly, and we anticipate sharing safety and efficacy data from that study in 2026,” Weber noted in the news release.
This trial is investigating vopimetostat plus the RAS(ON) multi-selective inhibitor daraxonrasib (RMC-6236) or the RAS(ON) G12D-selective inhibitor zoldonrasib (RMC-9805) in previously treated patients with MTAP-deleted/RAS-mutant pancreatic and lung cancer. Notably, the first dose-escalation cohort is fully enrolled with 7 patients. Both study combinations have been reported to be well tolerated at active exposure levels for each agent. The second cohort began enrollment in early October 2025. An additional cohort of first-line patients is expected to begin enrolling after the selection of go-forward doses. These data may support a pivotal trial of vopimetostat in patients with first-line, MTAP-deleted/RAS-mutated pancreatic cancer.
Furthermore, another planned clinical trial will enroll approximately 300 patients with MTAP-deleted pancreatic cancer who have received 1 prior line of therapy. Patients will receive vopimetostat daily at 250 mg or 1 of 4 standard chemotherapy regimens. Enrollment for this trial is anticipated to begin in 2026.
References
- Tango Therapeutics reports positive data from ongoing phase 1/2 study with vopimetostat (TNG462) in patients with MTAP-deleted Cancers. News release. Tango Therapeutics, Inc. October 23, 2025. Accessed October 23, 2025. https://ir.tangotx.com/news-releases/news-release-details/tango-therapeutics-reports-positive-data-ongoing-phase-12-study
- Safety and tolerability of TNG462 in patients with MTAP-deleted solid tumors. ClinicalTrials.gov. Updated May 6, 2025. Accessed October 23, 2025. https://clinicaltrials.gov/study/NCT05732831?term=TNG462&rank=2
