On June 8, 2026 Tango Therapeutics, Inc. (NASDAQ: TNGX), a clinical-stage biotechnology company committed to discovering and delivering the next generation of precision cancer medicines, reported positive initial data from its ongoing Phase 1/2 study of vopimetostat, an investigational PRMT5 inhibitor with first- and best-in-class potential, in combination with Revolution Medicines’ RAS(ON) inhibitors in patients with MTAP-deleted and RAS-mutant metastatic pancreatic ductal adenocarcinoma (PDAC).

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"In the first reported data from the clinical combinations of our PRMT5 inhibitor vopimetostat and RAS(ON) inhibitors, we saw extremely encouraging early results, with 92% of patients with PDAC in the vopimetostat plus daraxonrasib arm achieving an objective response, supporting the preclinical data showing synergistic activity of PRMT5 + RAS inhibition," said Malte Peters, MD, Chief Executive Officer of Tango Therapeutics. "Equally important, we are seeing encouraging signals of durability, with 90% of PDAC patients still progression free at 6 months of follow up. In addition, both combinations were generally well tolerated. Our primary focus is now to bring forward the PRMT5 plus RAS inhibitor combination approach in pancreatic cancer, while also looking toward important upcoming data readouts for vopimetostat single agent in lung cancer and TNG456 in GBM which we believe represents significant long-term opportunity for our company."

Dr. Peters continued, "These compelling results reinforce our belief that a vopimetostat-based combination with RAS inhibitors may be a path to a chemotherapy-free option for patients with MTAP-deleted pancreatic cancer. Given these data, we intend to prioritize advancement of the vopimetostat plus daraxonrasib combination into Phase 3 development in first-line, MTAP- deleted pancreatic cancer."

"Pancreatic cancer remains a largely intractable disease and an area where patients desperately need new therapies," said Brian Wolpin, MD, Director of the Hale Family Center for Pancreatic Cancer Research, Dana-Farber Cancer Institute. "In the front-line setting, chemotherapy has long been the standard of care, yet it presents significant tolerability challenges and overall limited efficacy against this aggressive disease. Building on the monotherapy activity already shown by these investigational PRMT5 and RAS(ON) targeted therapies, these early combination data demonstrated the potential to meaningfully reshape how we treat this disease with a precision-guided, chemotherapy-free approach."

Topline Phase 1/2 Clinical Data Highlights

As of a data cutoff date of May 28, 2026, 59 patients with previously treated MTAP-deleted and RAS-mutant pancreatic ductal adenocarcinoma (PDAC) or non-small cell lung cancer (NSCLC) were treated with a vopimetostat-based combination with either daraxonrasib (n=20 PDAC; n=5 NSCLC) or zoldonrasib (n=34 PDAC). All patients had advanced disease, including 70% with liver metastases in the daraxonrasib PDAC arm and 77% with liver metastases in the zoldonrasib arm, and were generally heavily pre-treated, with more than half receiving the combinations as third-line treatment.

Vopimetostat plus daraxonrasib combination

In the vopimetostat plus daraxonrasib dose escalation arm, patients received either vopimetostat 200 mg or 250 mg once daily (QD) plus daraxonrasib 100 mg QD. As of the data cutoff, 12 patients with PDAC and 3 patients with NSCLC were response evaluable with at least 14 weeks of follow up.

Data highlights include:

PDAC:
92% objective response rate (ORR) (11/12; 9 of 11 responses confirmed)
90% 6-month PFS rate
100% disease control rate (DCR)
NSCLC: 100% ORR, 3 of 3 responses confirmed
The vopimetostat + daraxonrasib was generally well tolerated across all dose levels with no new safety signals observed
Most adverse events were Grade 1 or 2 in severity. The most common treatment-related adverse events (TRAEs) were rash, stomatitis/mucositis and diarrhea.
There were no related Grade 4 or 5 adverse events
There were no dose-limiting toxicities (DLTs) at dose level 1 (vopimetostat 200 mg/daraxonrasib 100 mg). Three DLTs were reported in two patients at dose level 2 (vopimetostat 250 mg/daraxonrasib 100 mg), including one case of Grade 3 rash and one case of Grade 3 stomatitis and fatigue.
There were two dose reductions at dose level 1 and one dose reduction at dose level 2
There were no discontinuations due to adverse events

Development strategy:
Based on these data, Tango intends to rapidly advance this combination approach into Phase 3 development for patients with MTAP-deleted pancreatic cancer. Subject to feedback from regulatory authorities, the Company plans to initiate a Phase 3 randomized-controlled trial in front-line pancreatic cancer and evaluate opportunities to advance the second line combination towards registration phase.

Vopimetostat plus zoldonrasib combination (PDAC with MTAP deletion and KRAS G12D mutation)

In the vopimetostat plus zoldonrasib dose escalation arm, patients with PDAC received vopimetostat 200 mg or 250 mg QD plus zoldonrasib 600 mg or 1200 mg QD. As of the data cutoff date of May 28, 2026, 27 patients were response evaluable with at least 14 weeks of follow-up.

Data highlights include:

52% ORR (14/27; 10 of 14 responses confirmed)
74% 6-month PFS rate
96% DCR
The vopimetostat plus zoldonrasib combination was generally well tolerated at all dose levels with no new safety signals observed
Most adverse events were Grade 1 or 2. The most common TRAEs were nausea and vomiting.
There were no related Grade 4 or 5 adverse events
There were no DLTs
There was one dose reduction
There were no discontinuations due to adverse events

Upcoming Anticipated Milestones

Finalize design of Phase 3 randomized-controlled trial of the combination approach in front-line pancreatic cancer in 2H 2026
Disclose vopimetostat lung cancer monotherapy data in 2H 2026
Release initial TNG456 glioblastoma data 2H 2026
Present 2/3L PDAC vopimetostat + RAS(ON) inhibitors combination data at a scientific conference 2H 2026
Initiate Phase 1/2 vopimetostat + ERAS-0015 combination study 2H 2026

Investor Webcast and Conference Call Information
The Company will host a conference call to discuss these data at 8:00 a.m. ET today, June 8, 2026. The live webcast can be accessed under "Events & Presentations" in the Investors section of the company’s website at www.tangotx.com. The webcast will be available for replay for at least 30 days on the company website. Analysts who wish to join the teleconference and participate in Q&A should register here.

About Vopimetostat
Vopimetostat is a potentially best-in-class oral, once-daily, MTA-cooperative PRMT5 inhibitor that works selectively in cancer cells with MTAP (methylthioadenosine phosphorylase) deletion. MTAP deletions occur in 10-15% of all human cancers, including approximately 40% of pancreatic cancer and 15% of lung cancer. Vopimetostat is being evaluated as monotherapy and in combination clinical studies. In ongoing clinical studies, vopimetostat has demonstrated a favorable safety and tolerability profile to date and shown durable activity in multiple tumor types.

(Press release, Tango Therapeutics, JUN 8, 2026, View Source [SID1234666500])