bezuclastinib (PLX9486) / Daiichi Sankyo, Cogent Biosci - LARVOL DELTA

Peak part 1 summary: A phase 3, randomized, open-label, multicenter clinical study of bezuclastinib (CGT9486) and sunitinib combination versus sunitinib in patients with gastrointestinal stromal tumors (GIST). (ASCO-GI 2025) - P3 | "Funded by Cogent Biosciences Clinical Trial Registration Number: NCT05208047 Background: After initial response to first line therapy with imatinib, GISTs commonly progress due to secondary resistance mutations in KIT. Data from Peak Part 1 show an encouraging safety and tolerability profile generally consistent with published sunitinib monotherapy experience. ORR in evaluable pts from Part 1 was 20%; ORR in 2nd line pts was 33%. Part 2 of the Peak study is actively enrolling pts globally at the selected dose of bezuclastinib 600 mg QD + sunitinib 37.5 mg QD versus sunitinib 37.5 mg QD."

Clinical • P3 data • Stroma • Gastrointestinal Cancer • Oncology • KIT

Primary results of the phase 3 peak study of bezuclastinib + sunitinib vs sunitinib monotherapy in advanced gastrointestinal stromal tumors (GIST). (ASCO 2026) - P3 | "The Peak study evaluated efficacy and safety of bezuclastinib + sunitinib vs standard second-line sunitinib monotherapy in patients with advanced GIST who received prior imatinib therapy. Combined KIT inhibition with bezuclastinib + sunitinib significantly improved mPFS vs sunitinib monotherapy, reducing the risk of progression or death by 50% and increasing ORR from 26% to 46%. The combination was well tolerated with no new safety findings."

Metastases • Monotherapy • P3 data • Stroma • Gastrointestinal Disorder • Gastrointestinal Stromal Tumor • Neutropenia • Oncology • Sarcoma

Evaluating bezuclastinib for the treatment of advanced gastrointestinal stromal tumours. (PubMed, Expert Opin Pharmacother) - "After imatinib, several distinct secondary KIT-resistant clones may coexist within and between lesions, limiting the coverage of any single later-line inhibitor. This Drug Evaluation reviews the chemistry, active-state pharmacology, preclinical activity, pharmacokinetics, clinical efficacy, safety and regulatory status of bezuclastinib, with emphasis on its combination with sunitinib...Pending approval, it is likely to become a preferred second-line option for suitable patients with KIT-driven GIST. Mature survival, post-combination sequencing, resistance mechanisms, long-term patient-reported outcomes and real-world tolerability remain important evidence gaps."

Journal • Review • Gastrointestinal Stromal Tumor • Oncology • Sarcoma • PDGFRA

Phase 3 Peak Crossover: Bezuclastinib + Sunitinib Combination Following Sunitinib Monotherapy in Patients with GIST (ESMO 2026) - No abstract available

Clinical • Monotherapy • P3 data • Oncology • Sarcoma • Solid Tumor

Evaluation of Bone Formation Marker Changes in Summit, a Trial Assessing Bezuclastinib in Adults With Nonadvanced Systemic Mastocytosis: An Exploratory Analysis (SOHO 2026) - P2 | "Additionally, 26 patients had previously received treatment with bone-modifying agents, including denosumab (n = 7) and bisphosphonates (n = 19). Bezuclastinib appears to have a favorable impact on bone remodeling, with early stimulation of bone formation. These findings support its potential role in managing bone health in SM, where bone turnover is often disrupted. This is an encore abstract first presented at the American Academy of Allergy, Asthma & Immunology (AAAAI) 2026 annual meeting."

Clinical • Metastases • Oncology • COL1A2

Cogent Biosciences Announces FDA Acceptance of New Drug Application (NDA) for Bezuclastinib in Patients with Advanced Systemic Mastocytosis (AdvSM) (The Manila Times) - "PDUFA target action date set for June 29, 2027...In addition, the FDA communicated that at this time, there is no plan to hold an advisory committee, nor have they identified any potential review issues....The NDA acceptance is supported by data from the APEX pivotal trial..."

FDA filing • PDUFA • Hematological Malignancies

EFFICACY AND SAFETY OF BEZUCLASTINIB IN PATIENTS WITH ADVANCED SYSTEMIC MASTOCYTOSIS: PRIMARY RESULTS FROM THE APEX STUDY (EHA 2026) - "In the ITT population, median age (range) was 70 (43-87) years; 23 (28%) patients were female; 28 patients (35%; avapritinib, 7%; midostaurin, 30%) received prior KIT-targeted TKI therapy. Summary/Conclusion Bezuclastinib demonstrated high response rates, led to deep reductions in objective markers of MC burden, and was well-tolerated, with infrequent dose reductions and no discontinuations due to TRAEs. Positive results from Apex support bezuclastinib as a potential treatment for patients with AdvSM."

Clinical • Metastases • Aggressive Systemic Mastocytosis • Hematological Disorders • Hematological Malignancies • Leukemia • Mast Cell Leukemia • Myeloproliferative Neoplasm • Neutropenia • Thrombocytopenia

Cogent Biosciences establishes a long-term commercial supply arrangement with Hovione for manufacturing bezuclastinib formulations under a renewable multi-year agreement (StockTitan.net) - "Cogent will provide rolling quarterly forecasts and commit to purchase minimum percentages of its Product requirements from Hovione, with these percentages decreasing over time. The agreement has an initial five-year term and then renews automatically in successive two-year periods, unless either party gives written notice a specified time before a renewal."

Licensing / partnership • Aggressive Systemic Mastocytosis • Gastrointestinal Stromal Tumor

KIT D816V-Selective Tyrosine Kinase Inhibitors for the Treatment of Advanced Systemic Mastocytosis: A Systematic Review and Meta-Analysis of Efficacy and Safety Outcomes (SOHO 2026) - "Our findings reveal that avapritinib delivers the highest ORRs and deepest clinical remissions for AdvSM, reinforcing its role as a preferred frontline therapy. However, its significant association with severe neutropenia demands strict baseline patient selection and continuous hematologic monitoring. Alternatively, midostaurin and the investigational TKI bezuclastinib offer favorable safety profiles and may serve as preferable options for patients with a high baseline risk of hematologic toxicities."

Metastases • Retrospective data • Review • Oncology

The Effect of Bezuclastinib on the Pathobiology of Mastocytosis: Changes in Bone Marrow Mast Cells, Tryptase, and KIT p.D816V Variant Allele Frequency From the Pivotal Summit Trial (SOHO 2026) - "Substantial reductions of KIT p. D816V VAF, in some cases to undetectable levels, and normalization of ST and BM MC characteristics suggest a reversal of the underlying SM pathogenesis with bezuclastinib. KIT: KIT proto-oncogene, receptor tyrosine kinase."

Oncology

Urinary Mast Cell Metabolites Versus Serum Tryptase for Monitoring Clinical Response to Cytoreductive Therapy in Indolent Systemic Mastocytosis (SOHO 2026) - "Treatments included avapritinib (n = 27) and bezuclastinib (n = 2). Serum tryptase demonstrated the strongest association with clinical improvement and remains the most informative biomarker for monitoring CRT response in ISM. NMH also correlated with symptom improvement and may serve as a useful complementary biomarker, whereas 23-dinor-11β-PGF2α and LTE4 showed more variable changes and only limited correlation with clinical response. Although limited by the retrospective design and relatively small cohort size, these findings support the use of serum tryptase and NMH as the most clinically relevant biomarkers during CRT in ISM."

Clinical • Oncology

The Effect of Bezuclastinib on the Pathobiology of Advanced Systemic Mastocytosis: Results From the Pivotal APEX Trial (SOHO 2026) - "In the APEX trial, bezuclastinib demonstrated high response rates and significant changes in bone marrow MC burden, aggregation, immunophenotype, and morphology, as well as in serum tryptase and KIT p.D816V VAF. Substantial reductions in disease burden markers, to the extent of normalization/elimination in many cases, signifies modification of underlying AdvSM pathobiology with bezuclastinib. mIWG-MRT-ECNM: modified International Working Group–Myeloproliferative Neoplasms Research and Treatment–European Competence Network on Mastocytosis; ORR: overall response rate, TKI: tyrosine kinase inhibitor."

Metastases • Myeloproliferative Neoplasm • Oncology • IL2RA • TNFRSF8

Bezuclastinib Expanded Access Program for Patients With Systemic Mastocytosis (SOHO 2026) - P, P2 | "KIT: KIT proto-oncogene, receptor tyrosine kinase, WHO: World Health Organization. This is an encore abstract that was first presented at SOHO 2025."

Clinical • Aggressive Systemic Mastocytosis • Hematological Malignancies • Leukemia • Oncology

Expanded Results From the Phase 2 Summit Trial: Bezuclastinib in Adults With Nonadvanced Systemic Mastocytosis (SOHO 2026) - P2 | "Bezuclastinib demonstrated statistically and clinically significant improvements in MC disease and symptom burden vs placebo in patients with NonAdvSM. The treatment was generally well tolerated. This is an encore abstract first presented at the American Academy of Allergy, Asthma & Immunology (AAAAI) 2026 annual meeting."

Clinical • Metastases • P2 data • Oncology

Efficacy and Safety of Bezuclastinib in Patients With Advanced Systemic Mastocytosis: Results From the Apex Study (SOHO 2026) - "Bezuclastinib demonstrated high response rates, led to deep reductions in objective markers of MC burden, and was well-tolerated, supporting bezuclastinib as a potential treatment option in AdvSM. ALT: alanine aminotransferase, AST: aspartate aminotransferase, CR: complete response, CRh: CR with partial hematologic recovery, KIT: KIT proto-oncogene, receptor tyrosine kinase, mIWG-MRT-ECNM: modified International Working Group–Myeloproliferative Neoplasms Research and Treatment and European Competence Network on Mastocytosis. This is an encore abstract first presented at the European Hematology Association (EHA) 2026 Annual Meeting."

Clinical • Metastases • Hematological Malignancies • Myeloproliferative Neoplasm • Oncology

Anticipated Upcoming Milestones (Cogent Biosciences Press Release) - "(i) Potential FDA approval of bezuclastinib in GIST - PDUFA date of November 30, 2026; (ii) Potential FDA approval of bezuclastinib in NonAdvSM - PDUFA date of December 30, 2026."

PDUFA • Aggressive Systemic Mastocytosis

Cogent Biosciences…announced it has submitted its New Drug Application (NDA) to the U.S. Food and Drug Administration (FDA) for bezuclastinib in Advanced Systemic Mastocytosis (AdvSM). (StockTitan.net) - "The NDA submission is supported by data from the pivotal APEX trial, which were most recently presented at the 2026 European Hematology Association (EHA) Congress."

FDA filing • Aggressive Systemic Mastocytosis

Anticipated Upcoming Milestones (Cogent Biosciences Press Release) - "Announce top-line results from PEAK in November 2025. PEAK is a global, randomized Phase 3 clinical trial studying the combination of bezuclastinib and sunitinib versus sunitinib alone in patients with imatinib-resistant GIST; Announce top-line results from APEX in December 2025. APEX is a registration-directed, global, open-label trial in patients with AdvSM."

P2 data • P3 data: top line • Aggressive Systemic Mastocytosis • Gastrointestinal Stromal Tumor

Cogent Biosciences Announces Multiple Presentations at the European Hematology Association (EHA) 2026 Congress (Cogent Biosciences Press Release) - "Pivotal data from APEX trial in Advanced Systemic Mastocytosis accepted for oral presentation; Cogent’s third oral presentation of pivotal data with bezuclastinib at major medical meetings; Preclinical data from selective, potent JAK2 V617F program accepted for poster presentation."

JAK2V617F • P2 data • Preclinical • Aggressive Systemic Mastocytosis • Mast Cell Leukemia • Myeloproliferative Neoplasm

Cogent Biosciences Announces Detailed Data from APEX Pivotal Trial of Bezuclastinib in Patients with Advanced Systemic Mastocytosis at the 2026 European Hematology Association (EHA) Congress (GlobeNewswire) - "As of the updated data cutoff of March 31, 2026 in Part 2 of the APEX trial, 81 AdvSM patients were treated with 150 mg of bezuclastinib, including 57 patients with SM-AHN, 11 patients with ASM and 13 patients with MCL. The primary endpoint of response per mIWG-MRT-ECNM was assessed on 68 evaluable patients and showed 65% ORR (CR+CRh+PR+CI), including 57% of patients who achieved CR, CRh or PR as best response....Key secondary endpoint of response per pure pathological response (PPR) criteria was assessed on 81 patients which showed an 81% ORR (CR+CRh+PR)....Bezuclastinib demonstrated durable clinical activity and prolonged PFS with a 12-month PFS rate of 79% and a 12-month OS rate of 87%....APEX NDA to be submitted in June 2026."

FDA filing • P2 data • Aggressive Systemic Mastocytosis

(Peak) A Phase 3 Randomized Trial of CGT9486+Sunitinib vs. Sunitinib in Subjects With Gastrointestinal Stromal Tumors (clinicaltrials.gov) - P3 | N=482 | Recruiting | Sponsor: Cogent Biosciences, Inc. | Active, not recruiting ➔ Recruiting

Enrollment open • Gastrointestinal Stromal Tumor • Oncology • Sarcoma • KIT

THE EFFECT OF BEZUCLASTINIB ON THE PATHOBIOLOGY OF ADVANCED SYSTEMIC MASTOCYTOSIS: RESULTS FROM THE PIVOTAL APEX TRIAL (EHA 2026) - P2 | "Table 1: Reductions in BM Disease Markers Following Bezuclastinib Treatment Marker Baseline Bezuclastinib Cycle 3 Day 1 Bezuclastinib Cycle 6 Day 1 Mean [N] [N] BM MCs (biopsy), % 41 41 [81] 19 19 [74] 8 8 [61] BM MCs (aspirate), % 9 9 [67] 5 5 [46] 2 2 [32] CD25 Expression, % 88 88 [81] 53 53 [75] 31 31 [60] CD30 Expression, % 25 25 [80] 10 10 [75] 2 2 [60] Spindle-Shaped MCs (biopsy), % 59 59 [77] 34 34 [71] 30 30 [57] Spindle-Shaped MCs (aspirate), % 60 60 [43] 36 36 [24] 40 40 [17] Summary/Conclusion In patients with AdvSM from Apex, bezuclastinib demonstrated high response rates and significant changes in BM MC burden, aggregation, immunophenotype, and morphology, as well as in serum tryptase and KIT p.D816V VAF. Substantial reductions in objective markers of disease burden, to the extent of normalization/elimination in many cases, signifies modification of underlying AdvSM pathobiology with bezuclastinib treatment."

Metastases • Aggressive Systemic Mastocytosis • Hematological Malignancies • Leukemia • Mast Cell Leukemia • IL2RA • TNFRSF8

Industry Expert Theater: Efficacy and Safety From the Phase 3 PEAK Study in Advanced Gastrointestinal Stromal Tumors (GIST) (ASCO 2026) - "Review the novel combination of bezuclastinib + sunitinib from nonclinical TKI inhibition profiles and differentiated in vivo data through Peak trial results. Review efficacy & safety data and implications for how Peak may redefine the GIST treatment paradigm after decades of limited progress. Company: Cogent Biosciences Presenters: Dana Martin, PharmD, Senior Vice President, Global Medical Affairs, Cogent Biosciences John Robinson, PhD, Chief Scientific Officer, Cogent Biosciences Rachael Easton, MD, PhD, Senior Vice President, Clinical Development, Cogent Biosciences Location: Theater 2"

Clinical • Metastases • P3 data • Stroma • Gastrointestinal Stromal Tumor • Oncology • Sarcoma

Bezuclastinib Plus Sunitinib Meets PFS End Point in KIT-Mutant GIST (Cancer Network) - "The trial met its primary end point. Bezuclastinib plus sunitinib produced a median progression-free survival (PFS) of 16.5 months (95% CI, 13.8–19.2) compared with 9.2 months (95% CI, 7.2–11.0) for sunitinib alone, representing a 50% reduction in the risk of disease progression or death (HR, 0.50; 95% CI, 0.39–0.65; P <.0001)....The combination also demonstrated a significantly superior objective response rate (ORR) of 45.6% (95% CI, 38.6%–52.7%) vs 25.8% (95% CI, 20.0%–32.3%) for sunitinib monotherapy (P <.0001), with complete responses in 6.4% vs 1.9% of patients."

P3 data • Gastrointestinal Stromal Tumor

Cogent Biosciences Announces FDA Acceptance of New Drug Application (NDA) with Priority Review for Bezuclastinib in Combination with Sunitinib for Patients with GIST (GlobeNewswire) - "NDA acceptance with Priority Review builds upon previous assignment of Breakthrough Therapy Designation and Real-Time Oncology Review following Phase 3 PEAK results; PDUFA date set for November 30, 2026...In addition, the FDA communicated that at this time, there is no plan to hold an advisory committee, nor have they identified any potential review issues...Full results from the Phase 3 PEAK trial to be shared in oral presentation at ASCO on Saturday, May 30, 2026."

FDA filing • P3 data • PDUFA • Priority review • Gastrointestinal Stromal Tumor