Following a primary readout of the phase 3 PEAK trial at ASCO in late May, Cogent Biosciences seems poised to receive its first FDA approval with highly-innovative bezuclastinib in 2L GIST (following 1L failure on imatinib) with a PDUFA goal date of November 30, 2026.
Imatinib, which has been off-patent since 2020, remains the standard of care (SOC) in 1L GIST and has brought 5 year survival for advanced GIST patients to 56%. [1] However, once patients reach second line, they are left with treatment options that leave plenty of room for improvement. Unlike the currently approved tyrosine kinase inhibitors (TKIs), bezuclastinib is a highly selective inhibitor of mutant KIT, an oncogene acting as the driver in over 75% of gastrointestinal stromal tumor (GIST) cases. [2] This selectivity, when combined with a multi-kinase inhibitor such as sunitinib, offers improved coverage of post-imatinib resistance mutations.
In the phase 3 PEAK trial, combining bezuclastinib with the 2L SOC sunitinib resulted in a 50% reduction in the risk of disease progression or death, with the median progression-free survival increasing from 9.2 months on sunitinib alone to 16.5 months on the combination regimen. Adding bezuclastinib also delivered a 20 percentage point-improvement in overall response rate. [3]
Although overall survival data are not yet mature, the progression-free survival data are strongly suggestive of an improvement in OS. Using our historical oncology database which explores the relationship between mOS and mPFS across tumor types, Equinox Group estimates the base case mOS to be 45.0 months with the upside case being 51.4 months. These represent a 22% and 32% improvement over sunitinib monotherapy, respectively.
If we assume that Cogent will price bezuclastinib similarly to Sanofi’s KIT TKI Ayvakit (approved in 2020), we can see that despite the substantial cost increase when compared with generic sunitinib, bezuclastinib offers strong Clinical Innovation scores of 6.8% and 9.4% in the base and upside cases.
Figure 1: Drivers of Clinical Innovation - Base Case
Figure 2: Drivers of Clinical Innovation - Upside Case
These percentages represent the reduction in unmet medical need that a drug offers when compared to the standard of care. Historically, a Clinical Innovation score >5% predicts that a drug will be commercially successful, with scores >10% being characteristic of a market dominator. Under this framework, it is clear that bezuclastinib is commercially promising and a noteworthy advancement in the GIST paradigm.
This readout comes at an advantageous time for Cogent. Its closest competitor, Qinlock (ripretinib, Deciphera Pharmaceuticals), which previously failed to differentiate itself against sunitinib in the second-line population, won't deliver its own phase 3 results until the primary readout of the INSIGHT trial in December 2027. [4] Importantly, this trial is exclusively looking at a subset of patients harboring co-occurring KIT exon 11 + 17 and/or 18 mutations, a strategy informed by a retrospective analysis of the previous phase 3 INTRIGUE trial’s failure. [5] Qinlock's fourth-line approval and established manufacturing, along with physician familiarity suggest it could scale quickly in this second line subset if the INSIGHT trial succeeds. Cogent's task is therefore to capitalize on its one to two year lead and entrench bezuclastinib + sunitinib as the broad second-line standard of care before Qinlock enters the space.
[1] BRF14 data demonstrate long-term efficacy of imatinib in advanced GIST. OncLive. August 22, 2025. Accessed July 6, 2026. https://www.onclive.com/view/brf14-data-demonstrate-long-term-efficacy-of-imatinib-in-advanced-gist.
[2] Helbing A, Menon G. Gastrointestinal Stromal Tumors. [Updated 2025 Sep 14]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2026 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK554541/
[3] Andrew J. Wagner et al. Primary results of the phase 3 peak study of bezuclastinib + sunitinib vs sunitinib monotherapy in advanced gastrointestinal stromal tumors (GIST). J Clin Oncol 44, 11500-11500(2026).DOI:10.1200/JCO.2026.44.16_suppl.11500
[4] National Library of Medicine (US). ClinicalTrials.gov. Published February 17, 2023. Updated December 2025. Accessed July 6, 2026. https://clinicaltrials.gov/study/NCT05734105
[5] Heinrich MC et al. Ripretinib versus sunitinib in gastrointestinal stromal tumor: ctDNA biomarker analysis of the phase 3 INTRIGUE trial. Nat Med. 2024 Feb;30(2):498-506. doi: 10.1038/s41591-023-02734-5. Epub 2024 Jan 5. PMID: 38182785; PMCID: PMC10878977.