^
    1d
    KontRASt-R: Rollover Study for Participants Who Have Been Treated With and Are Continuing to Benefit From Opnurasib as a Single Agent or in Combination With Other Study Treatments (clinicaltrials.gov)
    P1/2, N=40, Recruiting, Novartis Pharmaceuticals | Not yet recruiting --> Recruiting
    Enrollment open
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    Erbitux (cetuximab) • Mekinist (trametinib) • Tevimbra (tislelizumab-jsgr) • batoprotafib (TNO155) • opnurasib (JDQ443)
    2d
    Combining the KRASG12C inhibitor adagrasib with anti-PD-1 immunotherapy improves overall survival and prevents recurrence in preclinical models of brain metastasis. (PubMed, Neurooncol Adv)
    Adagrasib with ICI improved long-term survival and blocked CNS progression in dual extra- and intracranial BM models.  These findings support investigation of adagrasib with ICI in patients with KRASG12C-mutant BM.
    Preclinical • Journal • PD(L)-1 Biomarker • IO biomarker
    |
    KRAS (KRAS proto-oncogene GTPase)
    |
    KRAS mutation
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    Krazati (adagrasib)
    2d
    KRAS Inhibitor Induced Cancer Cell Death Enhances Sensitivity to Immune-Mediated Bystander Killing of Drug-Resistant Subclones. (PubMed, Cancer Res)
    To investigate this, we developed a preclinical model that mimics the development of resistance to KRAS-G12C inhibitors (G12Ci), such as adagrasib and RMC-4998...Mechanistically, these combination therapies led to profound remodeling of the tumor immune microenvironment, making it less immunosuppressive, and promoted cancer cell death that primed an immune response, with an influx of cytotoxic T lymphocytes recognizing tumor associated antigens shared between G12Ci resistant and sensitive cancer cells. Promotion of immune-mediated bystander elimination of drug-resistant cells may provide a paradigm for tackling the problem of drug resistance in cancer more broadly.
    Journal • PD(L)-1 Biomarker • IO biomarker
    |
    KRAS (KRAS proto-oncogene GTPase)
    |
    KRAS mutation
    |
    Krazati (adagrasib) • RM-029
    5d
    Development and in vivo evaluation of 18F-labeled PET tracers covalently targeting KRAS-G12C for noninvasive cancer diagnosis and therapy monitoring. (PubMed, Theranostics)
    [18F]KRAS490 showed specific, blockable tumor uptake and favorable pharmacokinetics, making it a promising tracer for noninvasive imaging of KRAS-G12C mutant tumors. Its ability to penetrate the CNS supports potential application in imaging both peripheral and brain lesions.
    Preclinical • Journal
    |
    KRAS (KRAS proto-oncogene GTPase)
    |
    KRAS mutation • KRAS G12C • KRAS G12
    |
    Krazati (adagrasib)
    7d
    A Clinical Trial of Calderasib (MK-1084) and Durvalumab in People With Non-Small Cell Lung Cancer (MK-1084-015/KANDLELIT-015) (clinicaltrials.gov)
    P3, N=310, Recruiting, Merck Sharp & Dohme LLC | Not yet recruiting --> Recruiting
    Enrollment open
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    PD-L1 (Programmed death ligand 1) • KRAS (KRAS proto-oncogene GTPase)
    |
    KRAS mutation • KRAS G12C • KRAS G12
    |
    Imfinzi (durvalumab) • calderasib (MK-1084)
    8d
    Monoclonal antibodies targeting PCDH7 inhibit tumor growth and enhance immune responses in KRAS-mutant non-small cell lung cancer. (PubMed, Sci Adv)
    A lead mAb (mAb7) sensitized tumors to the US Food and Drug Administration-approved MAPK kinase inhibitor trametinib and the KRASG12C inhibitor adagrasib. Moreover, a murinized antibody (Ms-mAb7) improved antitumor immunity in a KrasG12D syngeneic tumor model by enhancing infiltration and activation of cytotoxic immune cells. These findings provide an important advance in the clinical development of PCDH7-targeting antibodies for lung cancer treatment.
    Journal
    |
    KRAS (KRAS proto-oncogene GTPase) • CDH23 (Cadherin Related 23)
    |
    KRAS mutation • KRAS G12D
    |
    Mekinist (trametinib) • Krazati (adagrasib)
    8d
    Real-world comparative effectiveness of sotorasib versus docetaxel monotherapy in second line and beyond for advanced or metastatic non-small cell lung cancer: A national database analysis from England. (PubMed, Lung Cancer)
    Sotorasib was associated with significantly improved OS, TTNTD, and TTDD compared with docetaxel in 2 L+ for locally advanced or metastatic NSCLC under real-world conditions in England.
    Journal • HEOR • Real-world evidence
    |
    KRAS (KRAS proto-oncogene GTPase)
    |
    KRAS mutation • KRAS G12C • KRAS G12
    |
    docetaxel • Lumakras (sotorasib)
    9d
    Standard Versus Reduced Sotorasib Dosing in KRAS G12C-Mutated Non-Small Cell Lung Cancer: A Systematic Review and Meta-Analysis-Have We Answered the Dosing Question? (PubMed, JCO Oncol Pract)
    The labeled 960 mg dose did not demonstrate meaningful improvement in efficacy, while toxicity remained substantial. These findings support efforts under Project Optimus to identify the lowest effective dose. Lower doses, including 240 mg, may provide comparable outcomes while reducing toxicity, pill burden, and treatment costs.
    Retrospective data • Journal
    |
    KRAS (KRAS proto-oncogene GTPase)
    |
    KRAS mutation • KRAS G12C • KRAS G12
    |
    Lumakras (sotorasib)
    12d
    LOXO-RAS-20001: Study of LY3537982 in Cancer Patients With a Specific Genetic Mutation (KRAS G12C) (clinicaltrials.gov)
    P1/2, N=540, Active, not recruiting, Eli Lilly and Company | Recruiting --> Active, not recruiting
    Enrollment closed
    |
    KRAS (KRAS proto-oncogene GTPase)
    |
    KRAS mutation • KRAS G12C • KRAS G12
    |
    Keytruda (pembrolizumab) • Erbitux (cetuximab) • cisplatin • carboplatin • pemetrexed • olomorasib (LY3537982)
    12d
    A Study of LY3537982 in Chinese Participants With Advanced Solid Tumors (clinicaltrials.gov)
    P1, N=12, Completed, Eli Lilly and Company | Active, not recruiting --> Completed | Trial completion date: Apr 2027 --> Mar 2026 | Trial primary completion date: Apr 2026 --> Jul 2025
    Trial completion • Trial completion date • Trial primary completion date
    |
    KRAS (KRAS proto-oncogene GTPase)
    |
    KRAS mutation • KRAS G12C • KRAS G12
    |
    olomorasib (LY3537982)
    13d
    A Study of Multiple Olomorasib (LY3537982) Capsules in Healthy Participants (clinicaltrials.gov)
    P1, N=120, Completed, Eli Lilly and Company | Recruiting --> Completed
    Trial completion
    |
    olomorasib (LY3537982)
    14d
    An Open-label, Multicenter, Phase II Clinical Study to Evaluate HRS-7058 in Patients With Pancreatic Cancer (clinicaltrials.gov)
    P2, N=92, Recruiting, Shandong Suncadia Medicine Co., Ltd. | Not yet recruiting --> Recruiting
    Enrollment open