^
    10d
    (Peak) A Phase 3 Randomized Trial of CGT9486+Sunitinib vs. Sunitinib in Subjects With Gastrointestinal Stromal Tumors (clinicaltrials.gov)
    P3, N=442, Active, not recruiting, Cogent Biosciences, Inc. | Trial primary completion date: Jul 2025 --> Sep 2025
    Trial primary completion date
    |
    sunitinib • bezuclastinib (PLX9486) • midazolam hydrochloride
    1m
    SARC044: A Phase II Trial of Bezuclastinib in Combination With Sunitinib in Patients With GIST (clinicaltrials.gov)
    P2, N=40, Active, not recruiting, Sarcoma Alliance for Research through Collaboration | Recruiting --> Active, not recruiting
    Enrollment closed
    |
    sunitinib • bezuclastinib (PLX9486)
    1m
    (Summit) A Study to Evaluate the Efficacy and Safety of CGT9486 Versus Placebo in Patients With Indolent or Smoldering Systemic Mastocytosis (clinicaltrials.gov)
    P2, N=237, Active, not recruiting, Cogent Biosciences, Inc. | Trial primary completion date: Sep 2025 --> May 2025
    Trial primary completion date
    |
    bezuclastinib (PLX9486)
    4ms
    Tyrosine Kinase Inhibitors for Gastrointestinal Stromal Tumor After Imatinib Resistance. (PubMed, Pharmaceutics)
    Sunitinib, regorafenib, and ripretinib are currently approved as standard second-, third-, and fourth-line therapies, each demonstrating efficacy against distinct mutational profiles. Avapritinib, notably effective against PDGFRA D842V mutations, represents a milestone for previously untreatable subgroups. Several alternative agents-such as nilotinib, masitinib, sorafenib, dovitinib, pazopanib, and ponatinib-have shown varying degrees of success in refractory cases or specific genotypes. Investigational compounds, including crenolanib, bezuclastinib, famitinib, motesanib, midostaurin, IDRX-42, and olverembatinib, are under development to address resistant or wild-type GISTs...Future strategies include precision medicine approaches such as ctDNA-guided therapy, rational drug combinations, and novel drug delivery systems to optimize bioavailability and reduce toxicity. Ongoing research will be crucial for refining treatment sequencing and expanding therapeutic options, especially for rare GIST subtypes.
    Review • Journal
    |
    KIT (KIT proto-oncogene, receptor tyrosine kinase) • PDGFRA (Platelet Derived Growth Factor Receptor Alpha)
    |
    KIT mutation • PDGFRA D842V • PDGFRA mutation
    |
    sorafenib • imatinib • sunitinib • Iclusig (ponatinib) • pazopanib • Tasigna (nilotinib) • Stivarga (regorafenib) • midostaurin • crenolanib (ARO-002) • Ayvakit (avapritinib) • Nailike (olverembatinib) • Qinlock (ripretinib) • dovitinib (TKI258) • famitinib (SHR 1020) • motesanib (AMG 706) • GSK6042981 • bezuclastinib (PLX9486) • Kinaction (masitinib)
    6ms
    New treatments for systemic mastocytosis in 2025. (PubMed, Curr Opin Allergy Clin Immunol)
    Despite the considerable therapeutic progress in recent years, systemic mastocytosis is an incurable disease. In the last 20 years, the management of systemic mastocytosis has transformed from a one-size-fits-all approach, characterized by nonspecific cytoreductive drugs, to a tailored strategy focused on increasingly precise molecular targets, with the most notable example being the KIT inhibitors. Recently, the FDA and EMA have approved two drugs for treating systemic mastocytosis: avapritinib and midostaurin. Moreover, numerous trials are currently assessing the efficacy of new molecules: most are testing new-generation KIT inhibitors (ripretinib, bezuclastinib, elenestinib, masitinib, nintedanib), others focusing on Bruton's kinase (TL-895), interleukin-6 (sarilumab), sialic acid-binding immunoglobulin-like lectin-8 (lirentelimab), mTOR and CD33, among others. Real-life data are needed to confirm preliminary preclinical results.
    Journal
    |
    IL6 (Interleukin 6) • CD33 (CD33 Molecule)
    |
    KIT mutation
    |
    imatinib • midostaurin • nintedanib • Ayvakit (avapritinib) • Qinlock (ripretinib) • bezuclastinib (PLX9486) • Kevzara (sarilumab) • Kinaction (masitinib) • elenestinib (BLU-263)
    7ms
    (Peak) A Phase 3 Randomized Trial of CGT9486+Sunitinib vs. Sunitinib in Subjects With Gastrointestinal Stromal Tumors (clinicaltrials.gov)
    P3, N=442, Active, not recruiting, Cogent Biosciences, Inc. | Recruiting --> Active, not recruiting
    Enrollment closed
    |
    sunitinib • bezuclastinib (PLX9486) • midazolam hydrochloride
    7ms
    Expanded Access to Bezuclastinib to be Coadministered With Sunitinib for Patients With Gastrointestinal Stromal Tumors (clinicaltrials.gov)
    P=N/A, N=0, Available, Cogent Biosciences, Inc.
    New trial
    |
    sunitinib • bezuclastinib (PLX9486)
    8ms
    Expanded Access to Bezuclastinib for Patients With NonAdvanced Systemic Mastocytosis or Advanced Systemic Mastocytosis (clinicaltrials.gov)
    P=N/A, N=0, Available, Cogent Biosciences, Inc.
    New trial
    |
    bezuclastinib (PLX9486)
    10ms
    CGT9486 (Formerly Known as PLX9486) as a Single Agent and in Combination With PLX3397 (Pexidartinib) or Sunitinib in Participants With Advanced Solid Tumors (clinicaltrials.gov)
    P1/2, N=51, Completed, Cogent Biosciences, Inc. | Phase classification: P1b --> P1/2
    Phase classification
    |
    KIT mutation
    |
    imatinib • sunitinib • Turalio (pexidartinib) • bezuclastinib (PLX9486)
    11ms
    (Summit) a Study to Evaluate the Efficacy and Safety of CGT9486 Versus Placebo in Patients with Indolent or Smoldering Systemic Mastocytosis (clinicaltrials.gov)
    P2, N=207, Active, not recruiting, Cogent Biosciences, Inc. | Recruiting --> Active, not recruiting
    Enrollment closed
    |
    bezuclastinib (PLX9486)
    1year
    (Summit) A Study to Evaluate the Efficacy and Safety of CGT9486 Versus Placebo in Patients With Indolent or Smoldering Systemic Mastocytosis (clinicaltrials.gov)
    P2, N=207, Recruiting, Cogent Biosciences, Inc. | N=138 --> 207
    Enrollment change • Metastases
    |
    bezuclastinib (PLX9486)
    1year
    CGT9486-20-201: (Apex) Bezuclastinib in Patients With Advanced Systemic Mastocytosis (clinicaltrials.gov)
    P2, N=140, Recruiting, Cogent Biosciences, Inc. | Trial completion date: Sep 2025 --> Jul 2026 | Trial primary completion date: Jan 2025 --> Jul 2025
    Trial completion date • Trial primary completion date • Metastases
    |
    bezuclastinib (PLX9486)