^
    6d
    A Study to Evaluate the Pharmacokinetics of Divarasib in Healthy Participants and Participants With Impaired Hepatic Function (clinicaltrials.gov)
    P1, N=40, Active, not recruiting, Genentech, Inc. | Recruiting --> Active, not recruiting
    Enrollment closed
    |
    divarasib (RG6330)
    7d
    Krascendo 170: A Study Evaluating the Safety, Activity, and Pharmacokinetics of Divarasib as a Single Agent or in Combination With Other Anti-Cancer Therapies in Participants With Previously Untreated Advanced or Metastatic Non-Small Cell Lung Cancer With a KRAS G12C Mutation (clinicaltrials.gov)
    P1/2, N=320, Recruiting, Hoffmann-La Roche | N=240 --> 320
    Enrollment change
    |
    Keytruda (pembrolizumab) • cisplatin • carboplatin • pemetrexed • divarasib (RG6330)
    2ms
    NAUTIKA1: A Study of Multiple Therapies in Biomarker-selected Participants With Resectable Stages IB-III Non-small Cell Lung Cancer (NSCLC) (clinicaltrials.gov)
    P2, N=99, Recruiting, Genentech, Inc. | Trial completion date: Mar 2029 --> May 2030 | Trial primary completion date: Dec 2025 --> Nov 2026
    Trial completion date • Trial primary completion date
    |
    PD-L1 (Programmed death ligand 1) • KRAS (KRAS proto-oncogene GTPase) • BRAF (B-raf proto-oncogene) • ALK (Anaplastic lymphoma kinase) • RET (Ret Proto-Oncogene) • ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS) • NTRK1 (Neurotrophic tyrosine kinase, receptor, type 1) • NTRK3 (Neurotrophic tyrosine kinase, receptor, type 3) • NTRK2 (Neurotrophic tyrosine kinase, receptor, type 2)
    |
    PD-L1 expression • KRAS mutation • KRAS G12C • BRAF mutation • BRAF V600 • RET fusion • ALK fusion • RET mutation • ROS1 fusion • KRAS G12
    |
    Tecentriq (atezolizumab) • Zelboraf (vemurafenib) • Rozlytrek (entrectinib) • Alecensa (alectinib) • Cotellic (cobimetinib) • Gavreto (pralsetinib) • divarasib (RG6330)
    2ms
    GO42144: A Study to Evaluate the Safety, Pharmacokinetics, and Activity of GDC-6036 Alone or in Combination in Participants With Advanced or Metastatic Solid Tumors With a KRAS G12C Mutation (clinicaltrials.gov)
    P1, N=498, Active, not recruiting, Genentech, Inc. | Recruiting --> Active, not recruiting | Trial completion date: Feb 2026 --> Sep 2026 | Trial primary completion date: Feb 2026 --> Sep 2026
    Enrollment closed • Trial completion date • Trial primary completion date
    |
    KRAS (KRAS proto-oncogene GTPase)
    |
    KRAS mutation • KRAS G12C • KRAS G12
    |
    Avastin (bevacizumab) • Erbitux (cetuximab) • Tecentriq (atezolizumab) • erlotinib • divarasib (RG6330) • Itovebi (inavolisib) • migoprotafib (RLY-1971)
    3ms
    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, Recruiting, Hoffmann-La Roche | Trial primary completion date: Sep 2026 --> Sep 2027
    Trial primary completion date
    |
    Lumakras (sotorasib) • Krazati (adagrasib) • divarasib (RG6330)
    3ms
    Krascendo 170: A Study Evaluating the Safety, Activity, and Pharmacokinetics of Divarasib in Combination With Other Anti-Cancer Therapies in Participants With Previously Untreated Advanced or Metastatic Non-Small Cell Lung Cancer With a KRAS G12C Mutation (clinicaltrials.gov)
    P1/2, N=240, Recruiting, Hoffmann-La Roche | Trial completion date: May 2027 --> Jan 2032 | Trial primary completion date: Sep 2025 --> Jan 2032
    Trial completion date • Trial primary completion date
    |
    Keytruda (pembrolizumab) • cisplatin • carboplatin • pemetrexed • divarasib (RG6330)
    3ms
    Krascendo 2: A Study Evaluating the Efficacy and Safety of Divarasib and Pembrolizumab Versus Pembrolizumab and Pemetrexed and Carboplatin or Cisplatin in Participants With Previously Untreated, KRAS G12C-Mutated, Advanced or Metastatic Non-Squamous Non-Small Cell Lung Cancer (clinicaltrials.gov)
    P3, N=600, Recruiting, Hoffmann-La Roche | Not yet recruiting --> Recruiting
    Enrollment open
    |
    Keytruda (pembrolizumab) • cisplatin • carboplatin • pemetrexed • divarasib (RG6330)
    3ms
    BFAST: A Study to Evaluate the Efficacy and Safety of Multiple Targeted Therapies as Treatments for Participants With Non-Small Cell Lung Cancer (NSCLC) (clinicaltrials.gov)
    P2/3, N=1000, Active, not recruiting, Hoffmann-La Roche | Trial completion date: Aug 2028 --> Oct 2026 | Trial primary completion date: Aug 2028 --> Oct 2026
    Trial completion date • Trial primary completion date • Tumor mutational burden
    |
    BRAF (B-raf proto-oncogene)
    |
    Avastin (bevacizumab) • cisplatin • Tecentriq (atezolizumab) • Zelboraf (vemurafenib) • carboplatin • gemcitabine • Rozlytrek (entrectinib) • docetaxel • Alecensa (alectinib) • Cotellic (cobimetinib) • pemetrexed • divarasib (RG6330)
    4ms
    A Study to Evaluate the Pharmacokinetics of Divarasib in Healthy Participants and Participants With Impaired Hepatic Function (clinicaltrials.gov)
    P1, N=40, Recruiting, Genentech, Inc. | Trial completion date: Jan 2027 --> Jun 2026 | Trial primary completion date: Oct 2026 --> May 2026
    Trial completion date • Trial primary completion date
    |
    divarasib (RG6330)
    5ms
    Single-Agent Divarasib in Patients With KRAS G12C-Positive Non-Small Cell Lung Cancer: Long-Term Follow-Up of a Phase I Study. (PubMed, J Clin Oncol)
    The median progression-free survival was 13.8 months (95% CI, 9.8 to 25.4) in the overall population (N = 65) and 15.3 months (95% CI, 12.3 to 26.1) among patients assigned to the 400-mg dose level (n = 44). With extended follow-up, divarasib demonstrated long-term safety and antitumor activity in patients with advanced KRAS G12C-positive NSCLC.
    P1 data • Journal
    |
    KRAS (KRAS proto-oncogene GTPase)
    |
    KRAS G12C • KRAS G12
    |
    divarasib (RG6330)
    5ms
    RIT1M90I is a driver of lung adenocarcinoma tumorigenesis and resistance to targeted therapy. (PubMed, Cancer Res)
    Finally, RIT1M90I drove resistance to the KRASG12C inhibitor, divarasib, and the combination with migoprotafib reverted this phenotype. Together, our data shows that RIT1M90I is a bona fide oncogenic driver of lung cancer and mediator of targeted therapy resistance as a co-occurring mutation and suggests that RIT1-altered cancer patients may benefit from combination treatments with a SHP2 inhibitor.
    Journal
    |
    KRAS (KRAS proto-oncogene GTPase) • RIT1 (Ras Like Without CAAX 1)
    |
    KRAS mutation
    |
    divarasib (RG6330) • migoprotafib (RLY-1971)
    5ms
    The complex journey of targeting RAS in oncology. (PubMed, BMC Cancer)
    This breakthrough has led to the development of targeted therapeutics, such as sotorasib and adagrasib, for KRAS G12C-mutated non-small cell lung cancer (NSCLC)...New inhibitors, such as LY3537982 or GDC-6036, are promising, but achieving effective and selective RAS inhibition remains a significant challenge...Challenges such as off-target effects and delivery issues remain significant barriers in the introduction of effective therapies based on RAS inhibitors. This overview highlights the evolving nature of targeting RAS in cancer therapy.
    Review • Journal
    |
    KRAS (KRAS proto-oncogene GTPase) • TP53 (Tumor protein P53)
    |
    TP53 mutation • KRAS mutation • KRAS G12C • RAS mutation • KRAS G12
    |
    Lumakras (sotorasib) • Krazati (adagrasib) • divarasib (RG6330) • olomorasib (LY3537982)