Tango Therapeutics Reports Positive Data from Ongoing Phase 1/2 Study with Vopimetostat (TNG462) in Patients with MTAP-deleted Cancers

Rhea-AI Summary

Tango Therapeutics (NASDAQ: TNGX) reported positive Phase 1/2 data for vopimetostat (TNG462) in MTAP-deleted cancers dated October 23, 2025. Across 94 evaluable patients, the overall ORR is 27%, disease control rate 78%, and median PFS 6.4 months. In 2L MTAP-del pancreatic cancer (n=39 at active doses) ORR 25% and mPFS 7.2 months; company plans a ~300-patient global randomized pivotal trial in 2026 at the FDA-aligned dose 250 mg QD. A histology-agnostic cohort (excluding pancreatic, lung, sarcoma) showed ORR 49% and mPFS 9.1 months. Safety at 250 mg QD was generally tolerable; most common TRAEs were nausea, anemia, fatigue, dysgeusia, thrombocytopenia.

Positive

• Overall ORR of 27% across 94 evaluable patients
• 2L MTAP-del pancreatic cancer ORR 25% and mPFS 7.2 months
• Histology-agnostic cohort ORR 49% and mPFS 9.1 months
• FDA-aligned go-forward dose of 250 mg QD enabling pivotal plans
• Planned ~300-patient randomized pivotal pancreatic trial in 2026

Negative

• No responses observed in sarcoma cohort (0/9 responses)
• Grade 3 anemia occurred in 13% of patients
• mPFS in 3L+ pancreatic patients was only 4.1 months

Insights

Clinical Oncology Strategist

Phase 1/2 MTAP-deleted data show clear activity and a defined regulatory path toward a 2026 pivotal in 2L pancreatic cancer.

Vopimetostat produced measurable single-agent activity across tumor types with an overall ORR of 27% and mPFS of 6.4 months, and notable signals in specific cohorts: 2L MTAP-deleted pancreatic cancer mPFS 7.2 months with ORR 25%, and a histology‑agnostic cohort ORR 49% with mPFS 9.1 months (excluding sarcoma). The company reports FDA alignment on a go-forward dose of 250 mg QD and plans a global randomized pivotal study of ~300 patients beginning in 2026, which creates a clear, near-term clinical development milestone.

Key dependencies and risks include confirmatory outcomes in the planned pivotal trial, durability of responses beyond the median follow-ups reported (median follow-up ranged from 7.8 months to 9.4 months), and safety in broader populations despite a favorable tolerability profile reported at 250 mg QD (no drug-related Grade 4/5 events; Grade 3 anemia 13%; dose reductions 8%). Data readouts from the combination program with Revolution Medicines and the planned pivotal enrollment pace are concrete items to watch in 2026 and will materially affect regulatory and commercial prospects.

– 2L MTAP-del pancreatic cancer median progression free survival (mPFS) 7.2 months with an objective response rate (ORR) of 25% – 

– Combination studies with RAS(ON) inhibitors ongoing, data anticipated 2026 – 

– 49% ORR and mPFS 9.1 months in histology agnostic cohort of multiple late line, difficult to treat cancers provide further evidence of strong activity – 

– Company to hold conference call today at 8:30am ET – 

BOSTON, Oct. 23, 2025 (GLOBE NEWSWIRE) -- Tango Therapeutics, Inc. (NASDAQ: TNGX), a clinical-stage biotechnology company committed to discovering and delivering the next generation of precision cancer medicines, today announced positive data from its ongoing Phase 1/2 study of vopimetostat (TNG462) in patients with MTAP-deleted cancers.

“Today, we are presenting a substantive dataset on our lead PRMT5 inhibitor vopimetostat, which has the potential to be a turning point for treatment of multiple difficult-to-treat MTAP-del cancers, beginning with pancreatic cancer,” said Barbara Weber, M.D., President and CEO of Tango Therapeutics. “Across the 16 cancer types enrolled in the trial, the ORR is 27% in patients with a median follow-up of 9.4 months, which supports the potential for vopimetostat as the best-in-class PRMT5 inhibitor. In 2L 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 QD, we anticipate that this study will enroll rapidly, underscoring the potential for vopimetostat to be the first MTAP-selective PRMT5 inhibitor to market.”

Dr. Weber continued, “Our ongoing study of vopimetostat in combination with two Revolution Medicines (RVMD) RAS(ON) inhibitors is enrolling rapidly and we anticipate sharing safety and efficacy data from that study in 2026. Today, we also announced data from the histology-agnostic cohort of the vopimetostat phase 1/2 trial, where we observed a 49% ORR and mPFS of 9.1 months (excluding sarcoma). These 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. 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.”

“Current standard of care for patients with advanced pancreatic cancer is multi-agent chemotherapy that confers modest benefit along with side effects that can adversely affect patient quality of life,” said Brian Wolpin, M.D., M.P.H., Director, Gastrointestinal Cancer Center and Hale Family Center for Pancreatic Cancer Research, Dana-Farber Cancer Institute. “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.”

Efficacy Results Across Study Indications:

• As of September 1, 2025, 179 patients were enrolled across all histologies, with 154 at active doses (200 mg and above). Ninety-four tumor evaluable patients were enrolled more than 6 months prior to the efficacy analysis and included regardless of outcome. Across cancer types:
  • ORR: 27%
  • DCR: 78%
  • mPFS: 6.4 months
• 37/94 patients remained on treatment as of September 1, 2025.
  

Efficacy Results in Pancreatic Cancer Patients

• As of September 1, 2025, 64 patients with pancreatic cancer were enrolled. 39 of these patients received active doses and were enrolled more than 6 months prior to the analysis; in these patients:
  • ORR in 2L pancreatic cancer patients: 25%
  • ORR for all pancreatic cancer patients: 15%
  • DCR for all pancreatic cancer patients: 71%
  • mPFS in 2L patients: 7.2 months
  • mPFS in 3L+ patients: 4.1 months
• Median follow up: 7.8 months
  

Development Strategy in Pancreatic Cancer

• Following consultation with the FDA on the trial design scheduled later this quarter, the company plans to start a global, randomized, pivotal study in patients with MTAP-del pancreatic cancer who have received one prior line of therapy, comparing patients treated with 250 mg QD vopimetostat to patients treated with one of four standard chemotherapy regimens. The company anticipates this study will enroll approximately 300 patients and is intended to begin enrollment in 2026.
• The phase 1/2 combination study of vopimetostat with RAS(ON) multi-selective inhibitor daraxonrasib, and RAS(ON) G12D-selective inhibitor zoldonrasib (both from Revolution Medicines, RVMD), is ongoing with robust enrollment in previously treated MTAP-del/RAS mut pancreatic and lung cancer. The first dose escalation cohort of this study has been fully enrolled (n=7) and backfill is ongoing. Vopimetostat in combination with both daraxonrasib and zoldonrasib have been well-tolerated to date with exposures in the active range for each compound. The second cohort was initiated in early October. A cohort of 1L patients is expected to begin enrolling after go-forward doses have been selected. The data from this study have the potential to support a pivotal study in 1L MTAP-del/RAS mut pancreatic cancer. Initial data from the Phase 1/2 study are anticipated in 2026.

Enrollment in Lung Cancer

• As of September 1, 2025, 41 patients with 2L+ lung cancer were enrolled, 12 of whom had received active doses and were enrolled more than 6 months prior to the analysis.
• Emerging data are consistent with expectations, and the company anticipates providing a safety and efficacy update in 2026.

Efficacy Results in the Histology Agnostic Cohort:

• As of September 1, 2025, 41 patients with 13 different cancers were enrolled at active doses and had received a first dose more than 6 months prior to the analysis. This cohort excludes pancreatic and lung cancers (being evaluated in histology-specific cohorts) and sarcomas (where no activity was observed, n=0/9 responses). In this histology agnostic cohort:
  • ORR: 49%
  • DCR: 89%
  • mPFS: 9.1 months

Safety and Tolerability
Consistent with previously reported data, vopimetostat is generally well tolerated at 250 mg QD, the go-forward dose agreed with the FDA, with a potentially best-in-class safety profile. The most common treatment-related adverse events (TRAEs), predominantly grade 1, were nausea (26%), anemia (20%), fatigue (19%), dysgeusia (19%) and thrombocytopenia (13%). No treatment-related Grade 4 or 5 events occurred. Grade 3 events were rare, with the exception of anemia which was observed in 13% of patients. No drug related dose discontinuations have occurred as of September 1, 2025, and only 8% of patients treated at 250 mg QD required dose reduction to 200 mg QD.

Study Design
The Phase 1/2 study (NCT05732831) is a multicenter, open-label, first in human study in solid tumor patients whose tumor has a confirmed homozygous MTAP deletion. The first part of the study was an open-label, dose escalation and the second part is an open label dose expansion/optimization in specific MTAP-deleted tumor types. 

Investor Webcast and Conference Call Information
The company will host a conference call to discuss these data at 8:30 a.m. ET today, October 23, 2025. 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 35% of pancreatic cancer and 15% of lung cancer. Vopimetostat is being evaluated as a 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.

About Tango Therapeutics
Tango Therapeutics is a clinical-stage biotechnology company dedicated to discovering novel drug targets and delivering the next generation of precision medicine for the treatment of cancer. Using an approach that starts and ends with patients, Tango leverages the genetic principle of synthetic lethality to discover and develop therapies that take aim at critical targets in cancer. For more information, please visit www.tangotx.com.

Forward-Looking Statements
Certain statements in this press release may be considered forward-looking statements. Forward-looking statements generally relate to future events, Tango’s future operating performance and goals, the anticipated benefits of therapies and combination therapies (that include a Tango pipeline product), as well as the expectations, beliefs and development objectives for Tango’s product pipeline and clinical trials. In some cases, you can identify forward-looking statements by terminology such as “may”, “should”, “expect”, “intend”, “will”, “goal”, “estimate”, “anticipate”, “believe”, “predict”, “designed,” “potential” or “continue”, or the negatives of these terms or variations of them or similar terminology. For example, implicit or explicit statements concerning the following include or constitute forward-looking statements Dr. Weber's and Dr. Wolpin's statements in this press release and statements regarding....: (i) the potential of the Company’s PRMT5 molecules, as both standalone treatments and in combination with RAS(ON)-inhibitors, including the Company’s belief that vopimetostat (TNG462) has the potential to play a major role in treating patients with MTAP-del cancers; (ii) the preclinical research of the Company’s PRMT5 inhibitors, as a monotherapy and in combination, and the expectation that they may pave the way for future development opportunities, including expectations that the combination of vopimetostat with RAS(ON) inhibitors may be an important new therapy for RAS-mut, MTAP-del cancers; (iii) expectations regarding the anticipated benefits of the Company’s molecules, development candidates and product candidates; (iv) expectations for vopimetostat and the belief that vopimetostat has the potential to be a best-in-class PRMT5 inhibitor for the treatment of MTAP-del pancreatic and lung cancers and first-to-market; (v) beliefs regarding the ability of the ongoing vopimetostat clinical trial to inform the initiation of a registrational trial in pancreatic cancer next year and our development strategy in lung cancer; (vi) the Company’s plans and timing for combination trials, including the ongoing Phase 1/2 clinical trial of vopimetostat with each of two RAS(ON) inhibitors from Revolution Medicines; (vii) the timing of the Company’s Phase 1/2 clinical trial in TNG456; (viii) expectations regarding the planned study design and interactions with the FDA related thereto; and (ix) the expected timing of: (a) clinical trial initiation, enrollment, dose escalation and dose expansion (including for combination studies); and (b) disclosing initial, interim, updated, additional and final clinical trial results (including for combination studies). Such forward-looking statements are subject to risks, uncertainties, and other factors which could cause actual results to differ materially from those expressed or implied by such forward-looking statements. These forward-looking statements are based upon estimates and assumptions that, while considered reasonable by Tango and its management, are inherently uncertain. New risks and uncertainties may emerge from time to time, and it is not possible to predict all risks and uncertainties. Factors that may cause actual results to differ materially from current expectations include, but are not limited to: the benefits of product candidates seen in preclinical tests and analyses may not be evident when tested in later preclinical studies or in clinical trials or when used in broader patient populations (if approved for commercial sale); Tango has limited experience conducting clinical trials (and does and will continue to rely on a third party to operate its clinical trials) and may not be able to commence its clinical trials (including opening clinical trial sites, dosing the first patient, and continued enrollment and dosing of an adequate number of clinical trial participants) when expected, may not be able to continue dosing, initiate dose escalation and/or dose expansion on anticipated timelines, and may not generate or report clinical trial results (including final, initial, interim, updated clinical trial results or additional safety and efficacy data and the establishment of proof-of-mechanism and proof-of-concept) in the anticipated timeframe (or at all); future clinical trial data releases may differ materially from initial or interim data from our current and future clinical trials; Tango’s pipeline products may not be safe and/or effective in humans; Tango has a limited operating history and has not generated any revenue to date from product sales, and may never become profitable; other companies may be able to identify and develop product candidates more quickly than the Company and commercially introduce the product prior to the Company; the Company may not be able to identify development candidates on the schedule it anticipates due to technical, financial or other reasons; the Company may not be able to file INDs for development candidates on time, or at all, due to technical or financial reasons or otherwise; the Company may utilize cash resources more quickly than anticipated; the Company will need to raise capital in the future and if we are unable to raise capital when needed or on attractive terms, we would be forced to delay, scale back or discontinue some of our development programs or future commercialization efforts (which may delay filing of INDs, dosing patients, initiation of dose expansion, reporting clinical trial results and filing new drug applications); the Company may be unable to advance our preclinical development programs into and through the clinic for safety or efficacy reasons or commercialize our product candidates or we may experience significant delays in doing so as a result of factors beyond our control; the Company may not be able to realize the benefits of orphan drug or Fast Track designation (and such designations may not advance any anticipated approval timelines); the expected benefits of our product candidates in patients as single agents and/or in combination may not be realized; the Company may experience delays or difficulties in the initiation, enrollment, or dosing of patients in clinical trials or the announcement of clinical trial results, Tango may not identify or discover additional product candidates or may expend limited resources to pursue a particular product candidate or indication and fail to capitalize on product candidates or indications that may be more profitable or for which there is a greater likelihood of success; the Company’s product candidates may cause adverse or other undesirable side effects (or may not show requisite efficacy) that could, among other things, delay or prevent regulatory approval; our dependence on one or a limited number third parties for conducting clinical trials and producing drug substance and drug product (including drug substance, which is currently sole sourced); government regulation may negatively impact the Company’s business, including the potential approval of the BIOSECURE Act; the impact of trade restrictions such as sanctions or tariffs, legal actions or enforcement and inflation rates on our business, financial condition, and results of operations; inadequate funding for or disruptions at the U.S. Food and Drug Administration or other government agencies may slow the time necessary for new drugs to be reviewed and/or approved or prevent these agencies from performing business functions on which the operation of our business may rely (which could negatively impact our business); uncertainty around the U.S. presidential administration's approach to governmental agencies and/or product candidate approvals may present challenges for our business or create a more costly environment in which to pursue the development of new therapeutic candidates; our success depends on our ability to obtain and maintain patent and other proprietary protection for our technology and product candidates; and the scope of intellectual property protection obtained may not be sufficiently broad. Additional information concerning risks, uncertainties and assumptions can be found in Tango’s filings with the Securities and Exchange Commission (SEC), including the risk factors referenced in Tango’s Annual Report on Form 10-K for the fiscal year ended December 31, 2024, as supplemented and/or modified by its most recent Quarterly Report on Form 10-Q. You should not place undue reliance on forward-looking statements in this press release, which speak only as of the date they are made and are qualified in their entirety by reference to the cautionary statements herein. Tango specifically disclaims any duty to update these forward-looking statements.

Investors and Media:
Elizabeth Hickin
IR@tangotx.com
media@tangotx.com

FAQ

What are the key efficacy results for TNGX vopimetostat reported October 23, 2025?

Across 94 evaluable patients ORR 27%, DCR 78%, and overall mPFS 6.4 months.

What were the 2L MTAP-del pancreatic cancer results for TNGX (vopimetostat)?

ORR 25% and median PFS 7.2 months in 2L MTAP-del pancreatic patients at active doses.

What did the histology-agnostic cohort show for TNGX vopimetostat (excluding sarcoma)?

Histology-agnostic cohort reported ORR 49%, DCR 89%, and mPFS 9.1 months.

What safety issues were reported for TNGX vopimetostat at 250 mg QD?

Generally tolerable; most common TRAEs were nausea (26%), anemia (20%) and fatigue (19%); Grade 3 anemia in 13%.

What is Tango’s development plan and timeline for TNGX vopimetostat in pancreatic cancer?

Company plans a global randomized pivotal ~300-patient trial in MTAP-del 2L pancreatic cancer to begin enrollment in 2026.

Will Tango report combination data with RAS(ON) inhibitors and when?

Combination studies with Revolution Medicines RAS(ON) inhibitors are ongoing and safety/efficacy data are anticipated in 2026.