^
    17d
    StrateGIST 1: First-in-human Study of IDRX-42 in Participants With Metastatic and/or Unresectable Gastrointestinal Stromal Tumors (clinicaltrials.gov)
    P1, N=278, Recruiting, IDRx Inc. - A GSK Company | Trial primary completion date: Mar 2027 --> Nov 2027
    Trial primary completion date • First-in-human
    |
    PDGFRA (Platelet Derived Growth Factor Receptor Alpha)
    |
    KIT mutation • PDGFRA mutation • PDGFRA exon 18 mutation
    |
    sunitinib • GSK6042981
    1m
    A Study of IDRX-42 (GSK6042981) Versus (vs) Sunitinib in Participants With Gastrointestinal Stromal Tumors After Imatinib Therapy (clinicaltrials.gov)
    P3, N=450, Not yet recruiting, GlaxoSmithKline
    New P3 trial
    |
    imatinib • sunitinib • GSK6042981
    3ms
    StrateGIST 1: First-in-human Study of IDRX-42 in Participants With Metastatic and/or Unresectable Gastrointestinal Stromal Tumors (clinicaltrials.gov)
    P1, N=269, Recruiting, IDRx Inc. - A GSK Company | Trial completion date: Sep 2026 --> Nov 2027 | Trial primary completion date: Apr 2026 --> Mar 2027
    Trial completion date • Trial primary completion date • First-in-human
    |
    PDGFRA (Platelet Derived Growth Factor Receptor Alpha)
    |
    KIT mutation • PDGFRA mutation • PDGFRA exon 18 mutation
    |
    sunitinib • GSK6042981
    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)
    over1year
    A First-in-human (FIH) Study of IDRX-42 in Participants With Metastatic and/or Unresectable Gastrointestinal Stromal Tumors (GIST) [Study ID: StrateGIST 1] (clinicaltrials.gov)
    P1, N=240, Recruiting, IDRx, Inc. | N=143 --> 240
    Enrollment change • Stroma • Metastases
    |
    PDGFRA (Platelet Derived Growth Factor Receptor Alpha)
    |
    KIT mutation • PDGFRA mutation • PDGFRA exon 18 mutation
    |
    sunitinib • GSK6042981
    almost2years
    KIT/PDGFRA inhibitors for the treatment of gastrointestinal stromal tumors: getting to the gist of the problem. (PubMed, Expert Opin Investig Drugs)
    Despite the outstanding results of first-line imatinib in advanced GIST, resistance ultimately occurs mainly through secondary mutations in KIT/PDGFRA...However, it is now recognized that the situation is more intricate, with various factors interacting with KIT and PDGFRA, playing a crucial role in the response and resistance to treatments. Future strategies in the management of advanced GIST should integrate driver inhibition with the blockade of other molecules to enhance cell death and establish enduring responses in patients.
    Journal • Stroma
    |
    KIT (KIT proto-oncogene, receptor tyrosine kinase) • PDGFRA (Platelet Derived Growth Factor Receptor Alpha)
    |
    KIT mutation • PDGFRA mutation
    |
    imatinib • Ayvakit (avapritinib) • Qinlock (ripretinib) • GSK6042981 • bezuclastinib (PLX9486)
    over2years
    Anti-tumor efficacy of the novel KIT inhibitor IDRX-42 (formerly M4205) in patient- and cell line-derived xenograft models of gastrointestinal stromal tumor (GIST). (PubMed, Clin Cancer Res)
    IDRX-42 showed significant antitumor activity in patient- and cell line-derived GIST xenograft models. The novel kinase inhibitor induced volumetric responses, decreased mitotic activity and had antiproliferative effects. In models with KIT exon 13 mutation IDRX-42 induced characteristic myxoid degeneration.
    Preclinical • Journal • Stroma
    |
    PDGFRA (Platelet Derived Growth Factor Receptor Alpha)
    |
    KIT mutation • PDGFRA mutation • KIT exon 13 mutation • KIT K642E • KIT D820G • KIT W557
    |
    imatinib • sunitinib • Ayvakit (avapritinib) • GSK6042981
    3years
    FIRST-IN-HUMAN PHASE 1/1B STUDY OF IDRX-42, A NOVEL ORAL TYROSINE KINASE KIT INHIBITOR, IN PARTICIPANTS WITH METASTATIC AND/OR UNRESECTABLE GASTROINTESTINAL STROMAL TUMORS (CTOS 2022)
    Objective: The majority of gastrointestinal stromal tumors (GISTs) are driven by constitutively activated kinases, either KIT or PDGFRA, and respond to treatment with tyrosine kinase inhibitors (TKI) such as imatinib, sunitinib, regorafenib, and ripretinib. Not applicable
    P1 data
    |
    KIT (KIT proto-oncogene, receptor tyrosine kinase) • PDGFRA (Platelet Derived Growth Factor Receptor Alpha)
    |
    KIT mutation • PDGFRA mutation • PDGFRA exon 18 mutation
    |
    imatinib • sunitinib • Stivarga (regorafenib) • Qinlock (ripretinib) • GSK6042981
    over3years
    A First-in-human (FIH) Study of IDRX-42 in Participants With Metastatic and/or Unresectable Gastrointestinal Stromal Tumors (clinicaltrials.gov)
    P1, N=143, Recruiting, IDRx, Inc. | Not yet recruiting --> Recruiting
    Enrollment open
    |
    PDGFRA (Platelet Derived Growth Factor Receptor Alpha)
    |
    KIT mutation • PDGFRA mutation • PDGFRA exon 18 mutation
    |
    sunitinib • GSK6042981
    over3years
    A First-in-human (FIH) Study of IDRX-42 in Participants With Metastatic and/or Unresectable Gastrointestinal Stromal Tumors (clinicaltrials.gov)
    P1, N=143, Not yet recruiting, IDRx, Inc.
    New P1 trial
    |
    PDGFRA (Platelet Derived Growth Factor Receptor Alpha)
    |
    KIT mutation • PDGFRA mutation • PDGFRA exon 18 mutation
    |
    sunitinib • GSK6042981