^
    2d
    KontRASt-06: Study of Efficacy and Safety of JDQ443 Single-agent as First-line Treatment for Patients With Locally Advanced or Metastatic KRAS G12C- Mutated Non-small Cell Lung Cancer With a PD-L1 Expression < 1% or a PD-L1 Expression ≥ 1% and an STK11 Co-mutation. (clinicaltrials.gov)
    P2, N=95, Active, not recruiting, Novartis Pharmaceuticals | Trial completion date: Nov 2027 --> Dec 2026
    Trial completion date • IO biomarker
    |
    PD-L1 (Programmed death ligand 1) • KRAS (KRAS proto-oncogene GTPase) • STK11 (Serine/threonine kinase 11)
    |
    PD-L1 expression • KRAS mutation • KRAS G12C • STK11 mutation • KRAS G12
    |
    opnurasib (JDQ443)
    3d
    Flourishing innovation in KRAS targeting: Recent advances in medicinal chemistry strategies and future perspectives. (PubMed, Bioorg Chem)
    The landmark approval of Sotorasib in 2021, the first covalent KRASG12C inhibitor, shattered this dogma, ushering in a new era of targeted therapy for KRAS-mutant cancers, which also has catalyzed an explosion of innovative strategies extending far beyond covalent G12C targeting...Additionally, it encompasses structure-activity relationship (SAR) investigations and activity optimization processes and pharmacokinetic properties studies of representative molecules. Furthermore, we critically evaluate existing challenges in developing small-molecule KRAS modulators while discussing emerging opportunities in overcoming on-target resistance, aiming to offer valuable insights and perspectives for future research in this rapidly evolving field.
    Review • Journal
    |
    KRAS (KRAS proto-oncogene GTPase)
    |
    KRAS mutation • KRAS G12D
    |
    Lumakras (sotorasib)
    4d
    KANDLELIT-014: A Clinical Study of MK-1084 in People With Advanced Solid Tumors (MK-1084-014) (clinicaltrials.gov)
    P2, N=150, Recruiting, Merck Sharp & Dohme LLC | Not yet recruiting --> Recruiting
    Enrollment open • Pan tumor
    |
    KRAS (KRAS proto-oncogene GTPase)
    |
    Erbitux (cetuximab) • MK-1084
    5d
    A Clinical Study of MK-1084 With Rosuvastatin and Metformin in Healthy People (MK-1084-016) (clinicaltrials.gov)
    P1, N=16, Active, not recruiting, Merck Sharp & Dohme LLC | Recruiting --> Active, not recruiting
    Enrollment closed
    |
    metformin • MK-1084
    6d
    Unlocking New Treatment Possibilities for Metastatic Endometrial Cancer With KRAS G12C Mutation. (PubMed, Case Rep Oncol Med)
    This case highlights the potential clinical utility of KRAS G12C inhibitors in EC and highlights the importance of molecular profiling in identifying actionable mutations that may guide treatment decisions. This report, contributing to the limited body of evidence that includes three prior cases evaluating the role of sotorasib and adagrasib across several solid malignancies, highlights the clinical and translational relevance of adagrasib in advancing precision-targeted therapy for KRAS G12C-mutated tumors.
    Journal
    |
    KRAS (KRAS proto-oncogene GTPase)
    |
    KRAS mutation • KRAS G12C • KRAS G12
    |
    Lumakras (sotorasib) • Krazati (adagrasib)
    9d
    A Study of MK-1084 in Participants With Hepatic Impairment and Healthy Volunteers (MK-1084-017) (clinicaltrials.gov)
    P1, N=58, Recruiting, Merck Sharp & Dohme LLC | Not yet recruiting --> Recruiting
    Enrollment open
    |
    MK-1084
    9d
    Krascendo 1: A Study Evaluating the Efficacy and Safety of Divarasib Versus Sotorasib or Adagrasib in Participants With Previously Treated KRAS G12C-positive Advanced or Metastatic Non-Small Cell Lung Cancer (clinicaltrials.gov)
    P3, N=320, Active, not recruiting, Hoffmann-La Roche | Recruiting --> Active, not recruiting
    Enrollment closed
    |
    Lumakras (sotorasib) • Krazati (adagrasib) • divarasib (RG6330)
    10d
    A Study to Evaluate the Pharmacokinetics of Divarasib in Healthy Participants and Participants With Impaired Hepatic Function (clinicaltrials.gov)
    P1, N=31, Completed, Genentech, Inc. | Active, not recruiting --> Completed | Trial completion date: Jun 2026 --> Nov 2025 | Trial primary completion date: May 2026 --> Nov 2025
    Trial completion • Trial completion date • Trial primary completion date
    |
    divarasib (RG6330)
    10d
    Efficacy and safety of garsorasib in patients with KRAS G12C-mutated advanced pancreatic cancer. (PubMed, Br J Cancer)
    Garsorasib demonstrated encouraging antitumor activity and a tolerable safety profile in patients with KRAS G12C-mutated advanced pancreatic cancer.
    Journal
    |
    KRAS (KRAS proto-oncogene GTPase)
    |
    KRAS mutation • KRAS G12C • KRAS G12
    |
    Anfangning (garsorasib)
    10d
    Glecirasib with or without cetuximab in previously treated locally advanced or metastatic colorectal cancer with KRASG12C mutation (JAB-21822-1002 and JAB-21822-1007): two open-label, non-randomised phase 1/2 trials. (PubMed, Lancet Gastroenterol Hepatol)
    Glecirasib monotherapy and its combination with cetuximab represent potential treatment options for patients with advanced, refractory colorectal cancer harbouring KRASG12C mutations. The promising efficacy and safety support further exploration of glecirasib-based combinations in earlier lines of treatment.
    P1/2 data • Journal
    |
    KRAS (KRAS proto-oncogene GTPase)
    |
    KRAS mutation • KRAS G12C • KRAS G12
    |
    Erbitux (cetuximab) • Airuikai (glecirasib)
    10d
    Activity of direct KRAS(G12C) inhibitors in preclinical models of pediatric cancer. (PubMed, Mol Cancer Ther)
    Here, we show that sotorasib, adagrasib, and the RAS-ON inhibitor RMC-6291 are effective in a neuroblastoma cell line altered by KRAS(G12C). Importantly, sotorasib also decreased ERK phosphorylation in a NRAS(G12C)-altered cell line xenograft model; however, this treatment did not prolong survival as a single agent. These results suggest that combinations of targeted agents that include sotorasib may be required for clinical benefit in pediatric patients with H- or NRAS(G12C)-altered malignancies in addition to those with KRAS(G12C)-altered malignancies.
    Preclinical • Journal
    |
    KRAS (KRAS proto-oncogene GTPase) • NRAS (Neuroblastoma RAS viral oncogene homolog)
    |
    KRAS mutation • NRAS G12
    |
    Lumakras (sotorasib) • Krazati (adagrasib) • elironrasib (RMC-6291)
    11d
    A Clinical Study of MK-1084 With Rosuvastatin and Metformin in Healthy People (MK-1084-016) (clinicaltrials.gov)
    P1, N=16, Recruiting, Merck Sharp & Dohme LLC | Not yet recruiting --> Recruiting
    Enrollment open
    |
    metformin • MK-1084