^
    over2years
    Phase I Study of JNJ-74699157 in Patients with Advanced Solid Tumors Harboring the KRAS G12C Mutation. (PubMed, Oncologist)
    Based on dose-limiting skeletal muscle toxicities and the lack of efficacy at the 100 mg dose, further enrollment was stopped. The safety profile of JNJ-74699157 was not considered favorable for further clinical development.
    P1 data • Journal
    |
    KRAS (KRAS proto-oncogene GTPase)
    |
    KRAS mutation • KRAS G12C • KRAS G12
    |
    JNJ-74699157
    over3years
    KRAS G12C-mutant non-small-cell lung cancer: biology, developmental therapeutics, and molecular testing. (PubMed, J Mol Diagn)
    These agents include sotorasib (AMG 510), adagrasib (MRTX 849), and JNJ-74699157. In addition to testing for known actionable oncogenic driver alterations in EGFR, ALK, ROS1, BRAF, MET exon 14 skipping, RET, and NTRK and for expression of PD-L1, pathologists, medical oncologists, and community practitioners will need to incorporate routine testing for emerging biomarkers such as MET amplification, ERBB2 (HER2), and KRAS mutations, particularly KRAS G12C, considering the promising development of direct inhibitors of KRAS protein.
    Review • Journal • PD(L)-1 Biomarker • IO biomarker
    |
    HER-2 (Human epidermal growth factor receptor 2) • PD-L1 (Programmed death ligand 1) • KRAS (KRAS proto-oncogene GTPase) • BRAF (B-raf proto-oncogene) • ALK (Anaplastic lymphoma kinase) • MET (MET proto-oncogene, receptor tyrosine kinase) • ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS) • NTRK (Neurotrophic receptor tyrosine kinase)
    |
    PD-L1 expression • KRAS mutation • KRAS G12C • HER-2 amplification • HER-2 mutation • MET amplification • MET exon 14 mutation • KRAS G12 • HER-2 amplification + PD-L1 expression • RET expression • NTRK expression
    |
    Lumakras (sotorasib) • Krazati (adagrasib) • JNJ-74699157
    4years
    First-in-Human Study of JNJ-74699157 in Participants With Tumors Harboring the KRAS G12C Mutation (clinicaltrials.gov)
    P1, N=10, Completed, Janssen Research & Development, LLC | Active, not recruiting --> Completed | Trial completion date: Mar 2021 --> Jul 2020 | Trial primary completion date: Mar 2021 --> Jul 2020
    Clinical • Trial completion • Trial completion date • Trial primary completion date
    |
    KRAS (KRAS proto-oncogene GTPase)
    |
    KRAS G12C • KRAS G12
    |
    JNJ-74699157
    over4years
    First-in-Human Study of JNJ-74699157 in Participants With Tumors Harboring the KRAS G12C Mutation (clinicaltrials.gov)
    P1, N=10, Active, not recruiting, Janssen Research & Development, LLC | Trial completion date: Jul 2023 --> Mar 2021 | Trial primary completion date: Jul 2023 --> Mar 2021
    Clinical • Trial completion date • Trial primary completion date
    |
    KRAS (KRAS proto-oncogene GTPase)
    |
    KRAS G12C • KRAS G12
    |
    JNJ-74699157
    over4years
    First-in-Human Study of JNJ-74699157 in Participants With Tumors Harboring the KRAS G12C Mutation (clinicaltrials.gov)
    P1; Recruiting --> Active, not recruiting | N=140 --> 10
    Enrollment change • Enrollment closed • Clinical
    |
    KRAS (KRAS proto-oncogene GTPase)
    |
    KRAS G12C • KRAS G12
    |
    JNJ-74699157
    over4years
    KRAS G12C Game of Thrones, which direct KRAS inhibitor will claim the iron throne? (PubMed, Cancer Treat Rev)
    Both AMG 510 from Amgen and MRTX849 from Mirati Therapeutics covalently binds to KRAS at the cysteine at residue 12, keeping KRAS in its inactive GDP-bound state and inhibiting KRAS-dependent signaling...In addition, two novel KRAS G12C inhibitors JNJ-74699157 and LY3499446 will have entered phase 1 studies by the end of 2019. Given the rapid clinical development of 4 direct covalent KRAS G12C inhibitors within a short period of time, understanding the similarities and differences among these will be important to determine the best treatment option based on tumor specific response (NSCLC versus colorectal carcinoma), potential resistance mechanisms (i.e. anticipated acquired mutation at the cysteine 12 residue) and central nervous system (CNS) activity. Additionally, further investigation evaluating the efficacy and safety of combination therapies with agents such as immune checkpoint inhibitors will be important next steps.
    Review • Journal
    |
    KRAS (KRAS proto-oncogene GTPase)
    |
    KRAS mutation
    |
    Lumakras (sotorasib) • Krazati (adagrasib) • JNJ-74699157 • LY3499446
    5years
    First-in-Human Study of JNJ-74699157 in Participants With Tumors Harboring the KRAS G12C Mutation (clinicaltrials.gov)
    P1; Not yet recruiting --> Recruiting
    Enrollment open • Clinical
    |
    KRAS (KRAS proto-oncogene GTPase)
    |
    KRAS G12C • KRAS G12
    |
    JNJ-74699157
    over5years
    First-in-Human Study of JNJ-74699157 in Participants With Tumors Harboring the KRAS G12C Mutation (clinicaltrials.gov)
    P1; N=140; Not yet recruiting; Sponsor:Janssen Research & Development, LLC
    New P1 trial • Clinical
    |
    KRAS (KRAS proto-oncogene GTPase)
    |
    KRAS G12C • KRAS G12
    |
    JNJ-74699157