Tango Therapeutics reported a 92% response rate and 90% six-month PFS with vopimetostat-daraxonrasib in MTAP-deleted pancreatic cancer, advancing the chemotherapy-free regimen into Phase 3 development.
Written By: Farha Farheen, PharmD
Reviewed By: Pharmacally Editorial Team
Tango Therapeutics reported encouraging early Phase 1/2 (NCT06922591) results for its investigational PRMT5 inhibitor vopimetostat combined with Revolution Medicines’ RAS(ON) inhibitor daraxonrasib in patients with MTAP-deleted, RAS-mutant metastatic pancreatic ductal adenocarcinoma (PDAC). The study enrolled heavily pretreated patients with advanced disease, many of whom had received multiple prior therapies.
Among 12 response-evaluable PDAC patients, the combination achieved a 92% objective response rate, including nine confirmed responses, and a 100% disease control rate. Importantly, 90% of patients remained progression-free at six months, while median progression-free survival had not yet been reached as of the May 28, 2026 data cutoff, suggesting durable clinical benefit.
Comparative Combination Data
The strongest activity was observed with the daraxonrasib combination, prompting Tango to prioritize the regimen for Phase 3 development. In a separate cohort of patients with MTAP-deleted, KRAS G12D-mutant PDAC, vopimetostat plus zoldonrasib achieved a 52% objective response rate, a 96% disease control rate, and a 74% six-month progression-free survival rate. These findings support advancing the daraxonrasib combination toward registrational development.
Activity Beyond Pancreatic Cancer
Early signs of activity also emerged in non-small cell lung cancer (NSCLC). All three response-evaluable patients treated with vopimetostat and daraxonrasib achieved confirmed responses, providing preliminary evidence that the combination strategy may extend beyond pancreatic cancer.
Safety and Tolerability
Both combinations were generally well tolerated. Most treatment-related adverse events were Grade 1 or 2. In the daraxonrasib arm, the most common adverse events were rash, stomatitis or mucositis, and diarrhea. Investigators reported no treatment-related Grade 4 or 5 adverse events and no treatment discontinuations. Dose-limiting toxicities occurred only at the higher vopimetostat dose level and included Grade 3 rash, stomatitis, and fatigue.
The zoldonrasib combination showed a similarly favorable safety profile, with nausea and vomiting reported most frequently. No dose-limiting toxicities, Grade 4 or 5 treatment-related adverse events, or treatment discontinuations were observed.
Precision-Guided Strategy
Metastatic PDAC remains one of the deadliest solid tumors, with limited treatment options and poor outcomes despite advances in chemotherapy. Vopimetostat is an oral, once-daily MTA-cooperative PRMT5 inhibitor that selectively targets tumors with MTAP deletion, a genetic alteration found in approximately 40% of pancreatic cancers and 15% of lung cancers.
Preclinical studies have shown synergistic activity between PRMT5 and direct RAS inhibition, supporting a targeted, potentially chemotherapy-free treatment approach for MTAP-deleted, RAS-driven cancers.
Clinical Development Path Forward
Chief Executive Officer Malte Peters said the findings reinforce the potential of combining PRMT5 and RAS inhibition and support advancing vopimetostat plus daraxonrasib into first-line Phase 3 development. Subject to regulatory feedback, Tango plans to finalize the design of a randomized Phase 3 trial in MTAP-deleted pancreatic cancer during the second half of 2026.
Additional milestones this year include disclosure of vopimetostat monotherapy data in lung cancer, initial clinical results for TNG456 in glioblastoma, and presentation of updated combination data at a scientific conference.
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About the Writer
Farha Farheen, PharmD (LinkedIn) is a pharmacy professional with a strong interest in pharmacovigilance and clinical research. She has completed her Doctor of Pharmacy (Pharm.D) along with her internship as a Clinical Pharmacist. She has hands-on experience in adverse drug reaction (ADR) reporting, safety data documentation, and pharmacovigilance workflows, and is proficient in using VigiFlow. She is also a patent holder for an antibacterial formulation enriched with bioactive substances, granted by the German Patent and Trademark Office.