^
    12ms
    SHP2 Inhibitor BBP-398 in Combination With Nivolumab in Patients With Advanced Non-Small Cell Lung Cancer With a KRAS Mutation (clinicaltrials.gov)
    P1, N=21, Terminated, Navire Pharma Inc., a BridgeBio company | N=45 --> 21 | Trial completion date: Jan 2025 --> Jul 2024 | Recruiting --> Terminated; Business reasons
    Enrollment change • Trial completion date • Trial termination • Combination therapy • Metastases
    |
    KRAS (KRAS proto-oncogene GTPase)
    |
    KRAS mutation
    |
    Opdivo (nivolumab) • BMS-986466
    12ms
    First-in-Human Study of the SHP2 Inhibitor BBP-398 in Patients With Advanced Solid Tumors (clinicaltrials.gov)
    P1, N=72, Terminated, Navire Pharma Inc., a BridgeBio company | N=130 --> 72 | Trial completion date: Feb 2025 --> Jul 2024 | Active, not recruiting --> Terminated; Business decision
    Enrollment change • Trial completion date • Trial termination • Metastases
    |
    EGFR (Epidermal growth factor receptor) • KRAS (KRAS proto-oncogene GTPase) • BRAF (B-raf proto-oncogene)
    |
    KRAS mutation • EGFR mutation • KRAS G12C • KRAS G12
    |
    BMS-986466
    12ms
    Argonaut: SHP2 Inhibitor BBP-398 in Combination With Sotorasib in Patients With Advanced Solid Tumors and a KRAS-G12C Mutation (clinicaltrials.gov)
    P1, N=28, Terminated, Navire Pharma Inc., a BridgeBio company | N=85 --> 28 | Trial completion date: Jun 2025 --> Aug 2024 | Recruiting --> Terminated; Business Reasons
    Enrollment change • Trial completion date • Trial termination • Combination therapy • Metastases
    |
    KRAS (KRAS proto-oncogene GTPase)
    |
    KRAS mutation • KRAS G12C • KRAS G12
    |
    Lumakras (sotorasib) • BMS-986466
    over1year
    BBP-398 in Combination With Osimertinib in Locally Advanced or Metastatic NSCLC Patients With EGFR Mutations (clinicaltrials.gov)
    P1, N=4, Terminated, LianBio LLC | Phase classification: P1a/1b --> P1 | N=52 --> 4 | Trial completion date: Jul 2026 --> Mar 2024 | Recruiting --> Terminated | Trial primary completion date: Dec 2025 --> Mar 2024; Business reason
    Phase classification • Enrollment change • Trial completion date • Trial termination • Trial primary completion date • Combination therapy • Metastases
    |
    Tagrisso (osimertinib) • BMS-986466
    over1year
    Phase I Study of the BBP-398 in Patients With Advance Solid Tumors (clinicaltrials.gov)
    P1, N=7, Terminated, LianBio LLC | N=28 --> 7 | Trial completion date: Sep 2024 --> Mar 2024 | Recruiting --> Terminated; Business reason
    Enrollment change • Trial completion date • Trial termination • Metastases
    |
    EGFR (Epidermal growth factor receptor)
    |
    BMS-986466
    over1year
    A Study of BMS-986466 With Adagrasib With or Without Cetuximab in Participants With Kirsten Rat Sarcoma Virus Glycine 12 to Cysteine (KRAS G12C)-Mutant Solid Tumors (clinicaltrials.gov)
    P1/2, N=5, Terminated, Bristol-Myers Squibb | N=410 --> 5 | Active, not recruiting --> Terminated; Business objectives have changed
    Enrollment change • Trial termination • Combination therapy • Metastases
    |
    KRAS (KRAS proto-oncogene GTPase)
    |
    Erbitux (cetuximab) • Krazati (adagrasib) • BMS-986466
    over1year
    A Study of BMS-986466 With Adagrasib With or Without Cetuximab in Participants With Kirsten Rat Sarcoma Virus Glycine 12 to Cysteine (KRAS G12C)-Mutant Solid Tumors (clinicaltrials.gov)
    P1/2, N=410, Active, not recruiting, Bristol-Myers Squibb | Recruiting --> Active, not recruiting | Trial completion date: Jul 2029 --> May 2024 | Trial primary completion date: Aug 2027 --> May 2024
    Enrollment closed • Trial completion date • Trial primary completion date • Combination therapy • Metastases
    |
    KRAS (KRAS proto-oncogene GTPase)
    |
    KRAS mutation • KRAS G12C • KRAS G12
    |
    Erbitux (cetuximab) • Krazati (adagrasib) • BMS-986466
    over1year
    First-in-Human Study of the SHP2 Inhibitor BBP-398 in Patients With Advanced Solid Tumors (clinicaltrials.gov)
    P1, N=130, Active, not recruiting, Navire Pharma Inc., a BridgeBio company | Recruiting --> Active, not recruiting
    Enrollment closed • Metastases
    |
    EGFR (Epidermal growth factor receptor) • KRAS (KRAS proto-oncogene GTPase) • BRAF (B-raf proto-oncogene)
    |
    KRAS mutation • EGFR mutation • KRAS G12C • KRAS G12
    |
    BMS-986466
    almost2years
    Discovery of 1H-pyrazolo[3,4-b]pyrazine derivatives as selective allosteric inhibitor of protein tyrosine phosphatase SHP2 for the treatment of KRAS-mutant non-small cell lung cancer. (PubMed, J Biomol Struct Dyn)
    In this study, we used the previously reported SHP2 allosteric inhibitor IACS-13909 as a lead drug for structural derivation and modification, and synthesized three SHP2 inhibitors...Furthermore, the combination therapy of compound 4b and KRAS inhibitor sotorasib would play a strong synergistic effect against NCI-H358 cells...Molecular docking study predicted that compound 4b bound to the allosteric site of SHP2 and formed H-bond interactions with key residues Thr108, Glu110, Arg111, and Phe113. In summary, this study aims to provide new ideas for the development of SHP2 allosteric inhibitors for the treatment of KRAS mutant non-small cell lung cancer.Communicated by Ramaswamy H. Sarma.
    Journal
    |
    KRAS (KRAS proto-oncogene GTPase)
    |
    KRAS mutation
    |
    Lumakras (sotorasib) • BMS-986466
    2years
    A Study of BMS-986466 With Adagrasib With or Without Cetuximab in Participants With Kirsten Rat Sarcoma Virus Glycine 12 to Cysteine (KRAS G12C)-Mutant Solid Tumors (clinicaltrials.gov)
    P1/2, N=410, Recruiting, Bristol-Myers Squibb | Not yet recruiting --> Recruiting
    Enrollment open • Combination therapy • Metastases
    |
    KRAS (KRAS proto-oncogene GTPase)
    |
    KRAS mutation • KRAS G12C • KRAS G12
    |
    Erbitux (cetuximab) • Krazati (adagrasib) • BMS-986466
    2years
    A Study of BMS-986466 With Adagrasib With or Without Cetuximab in Participants With Kirsten Rat Sarcoma Virus Glycine 12 to Cysteine (KRAS G12C)-Mutant Solid Tumors (clinicaltrials.gov)
    P1/2, N=410, Not yet recruiting, Bristol-Myers Squibb
    New P1/2 trial • Combination therapy • Metastases
    |
    KRAS (KRAS proto-oncogene GTPase)
    |
    KRAS mutation • KRAS G12C • KRAS G12
    |
    Erbitux (cetuximab) • Krazati (adagrasib) • BMS-986466
    over2years
    First-in-Human Study of the SHP2 Inhibitor BBP-398 in Patients With Advanced Solid Tumors (clinicaltrials.gov)
    P1, N=130, Recruiting, Navire Pharma Inc., a BridgeBio company | Trial completion date: Oct 2023 --> Feb 2025 | Trial primary completion date: Apr 2023 --> May 2024
    Trial completion date • Trial primary completion date • Metastases
    |
    EGFR (Epidermal growth factor receptor) • KRAS (KRAS proto-oncogene GTPase) • BRAF (B-raf proto-oncogene)
    |
    KRAS mutation • EGFR mutation • KRAS G12C • KRAS G12
    |
    BMS-986466