Cogent Biosciences Reports Positive Results from Bezuclastinib PEAK Phase 3 Trial in Gastrointestinal Stromal Tumors (GIST)

Rhea-AI Summary

Cogent Biosciences (Nasdaq: COGT) reported positive Phase 3 PEAK results for bezuclastinib + sunitinib in imatinib-resistant or intolerant GIST on Nov 10, 2025. The combination achieved mPFS 16.5 months vs 9.2 months for sunitinib (HR=0.50; 95% CI: 0.39–0.65; p<0.0001) and ORR 46% vs 26% (p<0.0001). Safety was generally tolerable; no new combination-specific risks identified. Cogent plans an NDA submission in 1H 2026, will present full PEAK data at a scientific conference in 1H 2026, and is hosting an investor webcast Nov 10, 2025 at 8:00 a.m. ET.

Positive

• mPFS 16.5 months vs 9.2 months (HR 0.50)
• Objective Response Rate 46% vs 26% (p<0.0001)
• Planned NDA submission in 1H 2026

Negative

• Grade 3+ ALT/AST increases 10.8% vs 1.4%
• Treatment discontinuations 7.4% vs 3.8% (combination vs mono)
• Overall survival data remain immature

Insights

Clinical oncology analyst

Phase 3 PEAK shows large PFS and ORR improvements for the bezuclastinib+sunitinib combination; NDA planned in 1H 2026.

Cogent demonstrated a median progression‑free survival of 16.5 months versus 9.2 months with monotherapy, a hazard ratio implying a 50% reduction in risk (HR=0.50, 95% CI: 0.39–0.65; p<0.0001). The trial also reported an objective response rate of 46% versus 26% (p<0.0001). These are clear, measurable efficacy gains on the trial's primary endpoint and a key secondary endpoint as stated.

The safety profile, as reported, showed higher rates of some Grade 3+ events on the combination (notably ALT/AST increases at 10.8% vs 1.4%) and higher discontinuations (7.4% vs 3.8%), but the company reports no unique risks beyond the known sunitinib profile and that most hepatic events were transient and resolved. Dependence on ongoing overall survival maturity and detailed safety tables remains; the company explicitly states survival data are immature and full data presentation is planned in 1H 2026.

Watch for the NDA submission in 1H 2026, the upcoming detailed PEAK data at a scientific conference in 1H 2026, and full safety and OS breakdowns upon presentation. Also note the announced APEX top‑line timing in December 2025 and other regulatory filings tied to bezuclastinib described in the release.

16.5 months median progression free survival (mPFS) for bezuclastinib plus sunitinib compared to 9.2 months mPFS for sunitinib monotherapy (HR=0.50, CI: 0.39-0.65; p<0.0001)

46% Objective Response Rate (ORR) reported for bezuclastinib combination compared to 26% ORR for sunitinib monotherapy (p<0.0001)

Safety profile of bezuclastinib combination was well tolerated with no unique risks observed with the combination when compared to the known safety profile of sunitinib

First positive Phase 3 trial in second-line GIST patients in over 20 years; Plan to submit NDA in 1H 2026 and present full PEAK results at a scientific conference in 1H 2026

Cogent to host investor webcast today at 8:00 am ET

WALTHAM, Mass. and BOULDER, Colo., Nov. 10, 2025 (GLOBE NEWSWIRE) -- Cogent Biosciences, Inc. (Nasdaq: COGT), a biotechnology company focused on developing precision therapies for genetically defined diseases, today reported positive data from its Phase 3 PEAK trial of bezuclastinib plus sunitinib in patients with imatinib-resistant or intolerant Gastrointestinal Stromal Tumors (GIST). The combination reached a median progression free survival (mPFS) of 16.5 months compared to sunitinib monotherapy, which reached a mPFS of 9.2 months (HR=0.50, CI: 0.39-0.65; p<0.0001). In addition, the combination of bezuclastinib with sunitinib resulted in a 46% objective response rate (ORR) compared to 26% with sunitinib monotherapy (p<0.0001). Based on these data, Cogent is on track to submit a new drug application (NDA) to the U.S. Food and Drug Administration (FDA) for bezuclastinib in GIST in the first half of 2026. Cogent also plans to present detailed results from the PEAK trial at an upcoming scientific conference in the first half of 2026.

“It is a historic day for Cogent Biosciences and the GIST patient community,” said Andrew Robbins, Cogent’s President and Chief Executive Officer. “We are extremely excited to announce positive results from the Phase 3 PEAK trial of bezuclastinib plus sunitinib, which have far surpassed our expectations for the activity of this combination in patients with imatinib-resistant or intolerant GIST. With these incredible results, including a greater than seven-month improvement on mPFS – reducing the rate of progression or death by half – the bezuclastinib combination is poised to become the new standard of care for treatment of second-line GIST patients. We are pleased to have an existing Expanded Access Program available to GIST patients who have an urgency to access this novel treatment immediately and look forward to partnering with regulatory agencies to make this combination broadly available to patients as soon as possible.” 

“The results from the PEAK trial are truly transformative and practice changing,” said Neeta Somaiah, M.D., Professor and Department Chair, Department of Sarcoma Medical Oncology, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX. “Following regulatory approval, I expect the bezuclastinib combination to be rapidly adopted as the new standard of care treatment for the majority of patients in the second-line GIST setting.”

“Imatinib-resistant or intolerant GIST patients have waited nearly 20 years for a new second-line treatment option. The remarkable results of the PEAK study suggest that wait has come to an end,” said Sara Rothschild, Executive Director, The Life Raft Group. “Like so many in the GIST community, we’ve actively followed this trial with real anticipation. On behalf of GIST patients around the world, we share our excitement for the hope that the bezuclastinib combination may bring these patients and their families.”

PEAK Phase 3 Trial Results

PEAK is a global, randomized Phase 3 clinical trial evaluating bezuclastinib in combination with sunitinib vs. sunitinib monotherapy in patients with imatinib-resistant or intolerant GIST. In the top-line results, as of the cutoff date, September 30, 2025, the bezuclastinib combination demonstrated a substantial and highly statistically significant clinical benefit on the primary endpoint of progression free survival (PFS), reducing risk of disease progression or death compared to the current standard of care by 50% (hazard ratio of 0.50, 95% CI: 0.39 – 0.65). mPFS, as assessed by blinded independent central review, was 16.5 months for the bezuclastinib combination vs. 9.2 months for sunitinib monotherapy. Additionally, the bezuclastinib combination demonstrated an unprecedented ORR in imatinib-resistant patients, with 46% of patients treated with the bezuclastinib combination achieving an objective response compared to 26% of patients treated with sunitinib. At the time of this analysis, data for overall survival remains immature.

Based on these data, and the number of ongoing patients receiving treatment on the bezuclastinib arm, the estimated mean duration of treatment for the bezuclastinib combination is projected to exceed 19 months.

Safety Data

As of the data cutoff, the bezuclastinib combination was generally well tolerated, and no unique risks were observed with the novel combination when compared to the known safety profile of sunitinib. The most commonly reported Grade 3+ treatment emergent adverse events in either arm (bezuclastinib combination vs. sunitinib) included: Hypertension (29.4% vs. 27.4%), Neutropenia (15.2% vs. 15.4%), ALT/AST increased (10.8% vs. 1.4%), Anemia (9.3% vs. 4.8%) and Diarrhea (7.8% vs. 7.2%). 7.4% of patients on the bezuclastinib combination and 3.8% of patients on sunitinib monotherapy discontinued study treatment(s) due to treatment related adverse events. Hepatic adverse events were predominantly transient and manageable lab abnormalities; the majority of which were low grade, non-serious, reversible and asymptomatic. In the combination arm, ALT/AST elevations led to bezuclastinib dose reductions in 12.7% of patients with only 3 subjects (1.5%) discontinuing bezuclastinib for ALT/AST elevations. All Grade 3 ALT/AST elevations resolved, and no Grade 4 elevations were reported across the study.

Complete analysis of the Phase 3 PEAK data is ongoing, and Cogent plans to present detailed results at a major medical conference in the first half of 2026. 

Anticipated Upcoming Milestones 

• Announce top-line results from the pivotal APEX trial in December 2025. APEX is a registration-directed, global, open-label trial in patients with Advanced Systemic Mastocytosis (AdvSM)
  

• Present multiple bezuclastinib presentations at the 67^th Annual Meeting of the American Society of Hematology (ASH), including two oral presentations from the pivotal SUMMIT trial in NonAdvanced Systemic Mastocytosis (NonAdvSM) patients

• Present initial data from Cogent’s novel JAK2 V617F inhibitor at ASH, showcasing its best-in-class potential
  

• Submit Cogent’s first NDA for bezuclastinib in NonAdvSM patients by the end of 2025
  

• Submit NDA for bezuclastinib in imatinib-resistant or intolerant GIST patients in the first half of 2026 

Webcast Information
Cogent will host a live webcast today, November 10, 2025 at 8:00 a.m. ET to discuss these results from PEAK with participation from Neeta Somaiah, M.D., Professor and Department Chair, Department of Sarcoma Medical Oncology, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX. The live event can be accessed on the Investors & Media page of Cogent’s website at investors.cogentbio.com. A replay of the webcast will be available approximately two hours after the completion of the event and will be archived for up to 30 days.

About Cogent Biosciences, Inc.
Cogent Biosciences is a biotechnology company focused on developing precision therapies for genetically defined diseases. The most advanced clinical program, bezuclastinib, is a selective tyrosine kinase inhibitor that is designed to potently inhibit key driver mutations in the KIT gene. One such mutation, KIT D816V, is responsible for driving systemic mastocytosis, a serious disease caused by unchecked proliferation of mast cells. Other KIT mutations, including several found on exon 17, are responsible for driving tumor growth in patients with advanced gastrointestinal stromal tumors (GIST). In addition to bezuclastinib, the Cogent Research Team is developing a portfolio of novel targeted therapies to help patients fighting serious, genetically driven diseases initially targeting mutations in FGFR2/3, ErbB2, PI3Kα, KRAS and JAK2. Cogent Biosciences is based in Waltham, MA and Boulder, CO. Visit our website for more information at www.cogentbio.com. Follow Cogent Biosciences on social media: X (formerly known as Twitter) and LinkedIn. Information that may be important to investors will be routinely posted on our website and X.

Forward Looking Statements
This press release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995, including, but not limited to, statements regarding: plans to submit an NDA for bezuclastinib in NonAdvSM patients by the end of 2025; plans to submit an NDA for bezuclastinib in imatinib-resistant GIST patients in the first half of 2026; plans to present full PEAK results at a scientific conference in the first half of 2026; the expectation that the bezuclastinib plus sunitinib combination is poised to become the new standard of care for second line GIST patients; plans to partner with regulatory agencies to make this combination broadly available to patients as soon as possible; the company’s projection that the estimated mean duration of treatment for the bezuclastinib combination will exceed 19 months; plans to announce top-line results from the APEX trial in December 2025; and plans to present multiple bezuclastinib presentations and initial data from Cogent’s novel JAK2 V617F inhibitor (including its best-in-class potential) at the 2025 ASH meeting. The use of words such as, but not limited to, “anticipate,” “believe,” “continue,” “could,” “estimate,” “expect,” “intend,” “may,” “might,” “plan,” “potential,” “predict,” “project,” “should,” “target,” “will,” or “would” and similar words expressions are intended to identify forward-looking statements. Forward-looking statements are neither historical facts nor assurances of future performance. Instead, they are based on our current beliefs, expectations and assumptions regarding the future of our business, future plans and strategies, our clinical results, the rate of enrollment in our clinical trials and other future conditions. New risks and uncertainties may emerge from time to time, and it is not possible to predict all risks and uncertainties. No representations or warranties (expressed or implied) are made about the accuracy of any such forward-looking statements. We may not actually achieve the forecasts or milestones disclosed in our forward-looking statements, and you should not place undue reliance on our forward-looking statements. Such forward-looking statements are subject to a number of material risks and uncertainties including but not limited to those set forth under the caption “Risk Factors” in Cogent's most recent Annual Report on Form 10-K, as supplemented by Quarterly Reports on Form 10-Q and other filings Cogent makes with the SEC from time to time. Any forward-looking statement speaks only as of the date on which it was made. Neither we, nor our affiliates, advisors or representatives, undertake any obligation to publicly update or revise any forward-looking statement, whether as a result of new information, future events or otherwise, except as required by law. These forward-looking statements should not be relied upon as representing our views as of any date subsequent to the date hereof.

Contact:
Christi Waarich
Senior Director, Investor Relations
christi.waarich@cogentbio.com
617-830-1653

FAQ

What were the PEAK trial mPFS results for COGT bezuclastinib plus sunitinib on Nov 10, 2025?

Median PFS was 16.5 months for the combination vs 9.2 months for sunitinib (HR=0.50; 95% CI: 0.39–0.65; p<0.0001).

How did objective responses compare in the PEAK trial for COGT (bezuclastinib) vs sunitinib?

ORR was 46% with the bezuclastinib combination vs 26% with sunitinib (p<0.0001).

When will Cogent (COGT) submit the NDA for bezuclastinib in GIST?

Cogent expects to submit the NDA for bezuclastinib in imatinib-resistant or intolerant GIST in 1H 2026.

Were there new safety risks reported for COGT bezuclastinib plus sunitinib in PEAK?

No unique combination-specific risks were reported; most common Grade 3+ events included hypertension and ALT/AST increases.

What hepatic safety signals occurred in the PEAK trial for COGT bezuclastinib?

Grade 3+ ALT/AST increases were 10.8% with the combination vs 1.4% with sunitinib; most were reversible and resolved.

Is overall survival (OS) mature in the PEAK trial for bezuclastinib (COGT)?

No; the company reported that OS data remain immature at the time of the top-line analysis.