Early-stage combination data from Boston-based Tango Therapeutics (Nasdaq: TNGX) reported a 92% objective response rate for vopimetostat, its oral MTA-cooperative PRMT5 inhibitor, combined with Revolution Medicines' (Nasdaq: RVMD) daraxonrasib in patients with MTAP-deleted, RAS-mutant metastatic pancreatic ductal adenocarcinoma — a signal that, if confirmed in randomized studies, could support a chemotherapy-free precision approach in a disease where cytotoxic regimens have long defined the standard of care. Vopimetostat exploits synthetic lethality in MTAP-deleted tumors, where accumulation of methylthioadenosine sensitizes cancer cells to PRMT5 inhibition; combining this mechanism with RAS(ON) suppression via daraxonrasib is designed to deliver deeper and more durable responses in the roughly 40% of pancreatic cancers harboring MTAP deletion.
Daraxonrasib is Revolution Medicines' pan-RAS(ON) inhibitor, designed to suppress active RAS signaling regardless of the specific KRAS mutation, and recently became one of the most closely watched pancreatic cancer programs after demonstrating an overall survival benefit in the Phase III RASolute 302 study.
Trial data
The data derive from an ongoing Phase I/II study evaluating vopimetostat-based combinations in MTAP-deleted, RAS-mutant solid tumors. As of a May 28, 2026 cutoff, 20 PDAC patients had been enrolled in the daraxonrasib arm; 12 were response-evaluable with at least 14 weeks of follow-up. Among these, 11 of 12 achieved an objective response (92% ORR), with 9 of 11 responses confirmed. A 100% disease control rate and a 90% six-month progression-free survival rate were also reported, with median PFS not yet reached. The patient population was heavily pretreated — more than half received the combination as third-line therapy — and 70% had liver metastases, underscoring the challenging clinical context. Three of five evaluable NSCLC patients also responded (100% ORR), though numbers remain too small for meaningful interpretation.
The combination was generally well tolerated at both dose levels tested (vopimetostat 200 mg or 250 mg plus daraxonrasib 100 mg once daily). Most adverse events were Grade 1 or 2; rash, stomatitis/mucositis, and diarrhea were the most common treatment-related events. Three dose-limiting toxicities were observed in two patients at the higher vopimetostat dose level, including Grade 3 rash and Grade 3 stomatitis with fatigue. No Grade 4 or 5 treatment-related adverse events and no discontinuations due to adverse events were reported.