82% objective response rate, median progression-free survival (PFS) not yet reached, and 9-month PFS-rate of 88% in patients with 2L/3L pancreatic cancer treated with vopimetostat plus daraxonrasib 

Vopimetostat combinations with RAS(ON) inhibitors daraxonrasib or zoldonrasib continued to be generally well-tolerated

Registrational Phase 3 study of vopimetostat plus daraxonrasib in front-line patients with MTAP-deleted pancreatic cancer expected to be initiated in 1H 2027

Tango Therapeutics, Inc. (NASDAQ: TNGX), a clinical-stage biotechnology company committed to delivering breakthrough targeted therapies that extend and improve the lives of patients with cancer, announced promising results 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) and non-small cell lung cancer (NSCLC). The results are being presented at the European Society for Medical Oncology (ESMO) 2026 Congress being held in Madrid.

As of the data cutoff date of August 20, 2026, updated data from the ongoing Phase 1/2 study demonstrated an 82% objective response rate (ORR), median PFS not yet reached, and a 9-month PFS rate of 88%, in 22 patients with 2L/3L MTAP-deleted/RAS-mutant PDAC who were efficacy-evaluable. The combination was generally well-tolerated in the 30 PDAC and NSCLC patients who received dose level 1.

“It is encouraging to see that the clinical activity and tolerability observed in our initial June 2026 dataset has been confirmed with longer follow-up and in a larger patient population, affirming our belief that the response rate and durability observed with vopimetostat plus daraxonrasib surpass any published PDAC datasets, even in front-line settings,” said Malte Peters, M.D., Chief Executive Officer and President of Tango Therapeutics. “Following discussions with the U.S. FDA, we are focused on initiating a planned registrational Phase 3 trial of vopimetostat with daraxonrasib in front-line patients with MTAP-deleted pancreatic cancer in the first half of 2027. Given the data generated to date, we view PRMT5 inhibition as an emerging backbone in combination treatment strategies in PDAC and beyond. As a leader in the development of PRMT5-targeted therapies, we are also encouraged by the potential combinations of vopimetostat with RAS inhibitors in MTAP wild-type tumors, which we believe could further expand the impact of PRMT5 inhibition across a broader population of patients with PDAC.”

"For patients with pancreatic cancer, a highly aggressive malignancy that often progresses despite prior treatment, achieving durable disease control remains a significant challenge," said Alexander Spira, M.D., Co-Director of the Virginia Cancer Specialists Research Institute, NEXT Oncology, an Avacare business, and a principal investigator of the study. “In this updated analysis, the large majority of patients remained progression-free at nine months despite being heavily pretreated, with more than half receiving the combination as third-line therapy. Achieving this level of durability with an oral, chemotherapy-free regimen is particularly meaningful for patients and highlights the potential of a vopimetostat combination to redefine the standard of care in a disease that has been notoriously difficult to treat.”

“The depth and durability of responses reported with the vopimetostat and daraxonrasib combination are encouraging, particularly for patients who had already received multiple lines of treatment. We are excited by the potential of this biomarker-driven, targeted therapy approach and believe these results warrant rapid evaluation in a larger, randomized Phase 3 trial,” said Anna Berkenblit, M.D., MMSc, Chief Scientific & Medical Officer of the Pancreatic Cancer Action Network (PanCAN). “The approval of daraxonrasib marked the beginning of a new era for the pancreatic cancer community after a long wait, and we are looking forward to the next major advance that will translate into meaningful progress for patients quickly.”

Regulatory Update
Following recent interactions with the U.S. Food and Drug Administration (FDA), Tango plans to initiate a global, randomized registrational trial evaluating the combination of vopimetostat with daraxonrasib in front-line patients with MTAP-deleted PDAC. The planned study will randomize patients 1:1 to receive either vopimetostat (200 mg once daily) plus daraxonrasib (100 mg once daily) or standard-of-care chemotherapy. The dual primary endpoints of the planned study are ORR and PFS, with overall survival as a key secondary endpoint. The Company anticipates initiating this study in the first half of 2027.

In addition, the Company intends to discuss the possibility of pursuing approval of this combination in patients with second-line PDAC with regulatory authorities.

Vopimetostat plus daraxonrasib data highlights
As of the data cutoff date of August 20, 2026, 34 patients with previously treated MTAP-deleted and RAS-mutant PDAC (n=29) or NSCLC (n=5) were treated with vopimetostat plus daraxonrasib. The majority of PDAC patients (13/22) who were efficacy-evaluable received the combination as third-line treatment. Efficacy-evaluable patients are those patients who received their first dose of treatment at least 14 weeks prior to the data cutoff date.

PDAC
In the vopimetostat plus daraxonrasib dose escalation arm, efficacy-evaluable patients received either vopimetostat 200 mg (n=19; dose level 1) or 250 mg (n=3; dose level 2) once daily (QD) plus daraxonrasib 100 mg QD. As of the data cutoff date of August 20, 2026, 22 patients were efficacy-evaluable, with median follow up of 7.1 months (range: 3.3-12.5 months).

Clinical activity, all dose levels:

• 82% ORR (18/22; 11 of 18 confirmed partial responses (cPRs), 7 unconfirmed partial responses; all unconfirmed responses confirmed after the data cutoff date)
• Median PFS not yet reached
• 88% 9-month PFS
• 100% disease control rate (DCR)

Safety and tolerability:

• Dose level 1 (n=25 safety-evaluable patients) was generally well-tolerated as of the data cutoff date:
  • There were no dose-limiting toxicities (DLTs)
  • There were no withdrawals due to treatment-related adverse events (TRAEs)
  • The rate of dose reduction was 20% (5/25)
  • There were no Grade 4 or 5 TRAEs
  • The rate of Grade 3 TRAEs was 40% (10/25)
  • The most common TRAEs were stomatitis (48%), rash (44%), and diarrhea (28%); all these events were Grade 1-2
• Dose level 2 (n=4 safety-evaluable patients) was not well-tolerated:
  • There were 3 DLTs in 2 patients

Safety-evaluable patients are those who received at least one dose of the applicable combination prior to the data cutoff date.

NSCLC

Clinical activity, dose level 1:

• 80% ORR (4/5 cPRs)
• 100% DCR

Safety and tolerability, dose level 1:

• There were no Grade 4 or 5 TRAEs
• The rate of Grade 3 TRAEs was 20% (1/5)
• The most common TRAEs were rash (100%), diarrhea (80%), stomatitis (40%), nausea (40%), and fatigue (40%); all these events were Grade 1-2.

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

In the vopimetostat plus zoldonrasib dose escalation arm, patients received vopimetostat 200 mg or 250 mg QD plus zoldonrasib 600 mg or 1200 mg QD across four dose levels (dose level 1: 200 mg/600 mg QD; dose level 2: 250 mg/600 mg QD; dose level 3: 250 mg/1200 mg QD; and dose level 4: 200 mg/1200 mg QD). As of the data cutoff date of August 20, 2026, 35 patients were efficacy-evaluable, meaning that they received their first dose of treatment at least 14 weeks prior to the data cutoff date. 39 patients were safety-evaluable, meaning they received at least one dose of this combination prior to the data cutoff date.

Data highlights include:

Clinical activity, all dose levels:

• 54% ORR (19/35; 18 cPRs,1 confirmed complete response)
• 61% 9-month PFS
• 97% DCR

Safety and tolerability, all dose levels:

Vopimetostat plus zoldonrasib was generally well-tolerated across dose levels:

• There were no DLTs
• There were no withdrawals due to TRAEs
• The rate of dose reduction was 15% (6/39)
• There were no Grade 5 TRAEs and there was one Grade 4 TRAE (3%)
• The rate of Grade 3 TRAEs was 28% (11/39)
• The most common TRAEs were nausea (39%), vomiting (39%), dysgeusia (28%) and fatigue (26%); all these events were Grade 1-2