^
    2d
    A Systematic Review of the Efficacy of KRAS p.G12C Inhibitors in Metastatic Colorectal Cancer: The Current State of Science. (PubMed, Cancer Invest)
    Adagrasib monotherapy yielded a median PFS of 4.4-5.6 months, an OS of 10-19.8 months, and an ORR of 19-23%, while its combination with cetuximab reported a PFS of 6.9 months, an OS of 13.4-15.9 months and an ORR of 34-46%...When combined with panitumumab, 960 mg sotorasib demonstrated better results with a PFS of 5.6-5.7 months, OS of 15.2 months and an ORR of 12.5-30%. Similarly, divarasib monotherapy led to a PFS of 5.6-6.9 months and an ORR of 20%, while its combination with cetuximab resulted in a PFS of 8.1 months and an ORR of 62.5%. Combination therapy of olomorasib and MK-1084, which are new-generation KRAS p.G12C (c.34G > T) inhibitors, with cetuximab also demonstrated highly promising efficacy with ORR of 38-44% and 50%, respectively...Initial results of KRAS-G12C inhibitors appear highly promising when they are combined with anti-EGFR therapy compared to historical therapeutic agents indicated for patients with chemotherapy-refractory CRC. Encouraging benefits warrant frontline trials with these novel therapeutics.
    Journal
    |
    KRAS (KRAS proto-oncogene GTPase)
    |
    KRAS mutation • KRAS G12C • KRAS G12
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    Erbitux (cetuximab) • Vectibix (panitumumab) • Lumakras (sotorasib) • Krazati (adagrasib) • divarasib (RG6330) • calderasib (MK-1084) • olomorasib (LY3537982)
    7d
    A Study of Olomorasib (LY3537982) in Healthy Participants (clinicaltrials.gov)
    P1, N=15, Not yet recruiting, Eli Lilly and Company
    New P1 trial
    |
    olomorasib (LY3537982)
    25d
    Therapeutic advances with KRASG12C inhibitors and combination strategies in non-small cell lung cancer brain metastases. (PubMed, Cancer Gene Ther)
    This article examines the clinical and translational application of specific next-generation blood-brain barrier penetrant KRASG12C inhibitors, such as sotorasib, adagrasib, olomorasib, RMC-6236, and D3S-001, and their rational integration with radiation therapy, targeted therapies, and immunotherapies to overcome therapeutic resistance in patients with NSCLC brain metastases. This review summarizes recent advances aimed at enhancing intracranial tumor control and overall survival in patients with NSCLC brain metastases through the use of next-generation KRASG12C inhibitors and multimodal therapies.
    Review • Journal • IO biomarker
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    KRAS (KRAS proto-oncogene GTPase)
    |
    KRAS mutation
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    Lumakras (sotorasib) • Krazati (adagrasib) • daraxonrasib (RMC-6236) • elisrasib (D3S-001) • olomorasib (LY3537982)
    2ms
    A Study of Olomorasib (LY3537982) in Healthy Japanese Participants (clinicaltrials.gov)
    P1, N=191, Completed, Eli Lilly and Company | Recruiting --> Completed
    Trial completion
    |
    olomorasib (LY3537982)
    3ms
    KaRAnaSa: A Study of Amivantamab and Olomorasib Combination Therapy in Participants With Metastatic Non-Small Cell Lung Cancer (clinicaltrials.gov)
    P1/2, N=60, Recruiting, Janssen Research & Development, LLC | Not yet recruiting --> Recruiting
    Enrollment open
    |
    KRAS (KRAS proto-oncogene GTPase)
    |
    Rybrevant (amivantamab-vmjw) • olomorasib (LY3537982)
    3ms
    Efficacy and Safety of Olomorasib in Combination with Pembrolizumab in Treatment of Patients with KRAS G12C-Mutant Advanced NSCLC. (PubMed, J Thorac Oncol)
    Olomorasib + pembrolizumab demonstrated manageable safety and promising antitumor activity in patients with KRAS G12C-mutant advanced NSCLC across PD-L1 expression levels, especially in the high PD-L1 first-line setting.
    Journal • PD(L)-1 Biomarker • IO biomarker
    |
    KRAS (KRAS proto-oncogene GTPase)
    |
    PD-L1 expression • KRAS mutation • KRAS G12C • KRAS G12
    |
    Keytruda (pembrolizumab) • olomorasib (LY3537982)
    4ms
    A Study of Olomorasib (LY3537982) in Healthy Japanese Participants (clinicaltrials.gov)
    P1, N=188, Recruiting, Eli Lilly and Company | Not yet recruiting --> Recruiting
    Enrollment open
    |
    olomorasib (LY3537982)
    4ms
    KaRAnaSa: A Study of Amivantamab and Olomorasib Combination Therapy in Participants With Metastatic Non-Small Cell Lung Cancer (clinicaltrials.gov)
    P1/2, N=60, Not yet recruiting, Janssen Research & Development, LLC
    New P1/2 trial
    |
    KRAS (KRAS proto-oncogene GTPase)
    |
    Rybrevant (amivantamab-vmjw) • olomorasib (LY3537982)
    4ms
    A Phase 3, Multicenter, Double-Blind, Placebo-controlled Study Assessing the Efficacy and Safety of Olomorasib in Combination with Standard of Care Immunotherapy in Participants with Resected or Unresectable KRAS G12C-Mutant, Non-Small Cell Lung Cancer - SUNRAY-02 (ChiCTR2500111173)
    P3, N=700, Not yet recruiting, Guangdong Provincial People's Hospital(Guangdong Academy of Medical Sciences); Guangdong Provincial People's Hospital(Guangdong Academy of Medical Sci
    New P3 trial • IO biomarker
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    PD-L1 (Programmed death ligand 1) • KRAS (KRAS proto-oncogene GTPase)
    |
    PD-L1 expression • KRAS mutation • KRAS G12C • KRAS G12
    |
    Keytruda (pembrolizumab) • Imfinzi (durvalumab) • olomorasib (LY3537982)
    5ms
    A Study of LY3537982 in Participants With Kidney Problems Compared With Participants With Normal Kidney Function (clinicaltrials.gov)
    P1, N=32, Recruiting, Eli Lilly and Company | Not yet recruiting --> Recruiting
    Enrollment open
    |
    olomorasib (LY3537982)
    5ms
    A Study of Multiple Olomorasib (LY3537982) Capsules in Healthy Participants (clinicaltrials.gov)
    P1, N=120, Recruiting, Eli Lilly and Company | Not yet recruiting --> Recruiting
    Enrollment open
    |
    olomorasib (LY3537982)
    6ms
    A Study of Olomorasib (LY3537982) in Participants With Hepatic Impairment and Healthy Participants (clinicaltrials.gov)
    P1, N=46, Completed, Eli Lilly and Company | Recruiting --> Completed
    Trial completion
    |
    olomorasib (LY3537982)