^
    21d
    Study to Evaluate the Safety, Pharmacokinetics, and Activity of GDC-1971 in Combination With Either Osimertinib in Participants With Unresectable, Locally Advanced, or Metastatic Non-Small Cell Lung Cancer, or With Cetuximab in Participants With Metastatic Colorectal Cancer (clinicaltrials.gov)
    P1, N=10, Completed, Genentech, Inc. | Active, not recruiting --> Completed | N=172 --> 10 | Trial completion date: Dec 2026 --> Sep 2025 | Trial primary completion date: Dec 2026 --> Sep 2025
    Trial completion • Enrollment change • Trial completion date • Trial primary completion date
    |
    KRAS (KRAS proto-oncogene GTPase) • BRAF (B-raf proto-oncogene) • NRAS (Neuroblastoma RAS viral oncogene homolog)
    |
    BRAF V600E • EGFR mutation • BRAF V600 • EGFR L858R • EGFR exon 19 deletion • EGFR positive
    |
    Erbitux (cetuximab) • Tagrisso (osimertinib) • migoprotafib (RLY-1971)
    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)
    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
    A Study to Evaluate the Safety, Pharmacokinetics, and Activity of GDC-1971 in Combination With Atezolizumab in Participants With Locally Advanced or Metastatic Solid Tumors (clinicaltrials.gov)
    P1, N=57, Completed, Genentech, Inc. | Active, not recruiting --> Completed | N=232 --> 57 | Trial completion date: Mar 2026 --> Jun 2025 | Trial primary completion date: Mar 2026 --> Jun 2025
    Trial completion • Enrollment change • Trial completion date • Trial primary completion date
    |
    EGFR (Epidermal growth factor receptor) • BRAF (B-raf proto-oncogene) • ALK (Anaplastic lymphoma kinase)
    |
    PD-L1 expression • BRAF wild-type
    |
    Tecentriq (atezolizumab) • migoprotafib (RLY-1971)
    10ms
    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, Recruiting, Genentech, Inc. | Trial primary completion date: Mar 2025 --> Feb 2026
    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)
    11ms
    A Study to Evaluate the Safety, Pharmacokinetics, and Activity of GDC-1971 in Combination With Atezolizumab in Participants With Locally Advanced or Metastatic Solid Tumors (clinicaltrials.gov)
    P1, N=232, Active, not recruiting, Genentech, Inc. | Trial completion date: May 2025 --> Mar 2026 | Trial primary completion date: May 2025 --> Mar 2026 | Recruiting --> Active, not recruiting
    Enrollment closed • Trial completion date • Trial primary completion date
    |
    EGFR (Epidermal growth factor receptor) • BRAF (B-raf proto-oncogene) • ALK (Anaplastic lymphoma kinase)
    |
    PD-L1 expression • BRAF wild-type
    |
    Tecentriq (atezolizumab) • migoprotafib (RLY-1971)
    12ms
    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, Recruiting, Genentech, Inc. | Trial completion date: Nov 2024 --> Mar 2026 | Trial primary completion date: Nov 2024 --> Mar 2025
    Trial completion date • Trial primary completion date • Combination therapy • Metastases
    |
    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)
    1year
    A Study to Evaluate the Safety, Pharmacokinetics, and Activity of GDC-1971 in Combination With Atezolizumab in Participants With Locally Advanced or Metastatic Solid Tumors (clinicaltrials.gov)
    P1, N=232, Recruiting, Genentech, Inc. | Active, not recruiting --> Recruiting
    Enrollment open
    |
    EGFR (Epidermal growth factor receptor) • BRAF (B-raf proto-oncogene) • ALK (Anaplastic lymphoma kinase)
    |
    PD-L1 expression • BRAF wild-type
    |
    Tecentriq (atezolizumab) • migoprotafib (RLY-1971)
    over1year
    Study to Evaluate the Safety, Pharmacokinetics, and Activity of GDC-1971 in Combination With Either Osimertinib in Participants With Unresectable, Locally Advanced, or Metastatic Non-Small Cell Lung Cancer, or With Cetuximab in Participants With Metastatic Colorectal Cancer (clinicaltrials.gov)
    P1, N=172, Active, not recruiting, Genentech, Inc. | Recruiting --> Active, not recruiting
    Enrollment closed • Combination therapy • Metastases
    |
    KRAS (KRAS proto-oncogene GTPase) • BRAF (B-raf proto-oncogene) • NRAS (Neuroblastoma RAS viral oncogene homolog)
    |
    Erbitux (cetuximab) • Tagrisso (osimertinib) • migoprotafib (RLY-1971)
    over1year
    A Study to Evaluate the Safety, Pharmacokinetics, and Activity of GDC-1971 in Combination With Atezolizumab in Participants With Locally Advanced or Metastatic Solid Tumors (clinicaltrials.gov)
    P1, N=232, Active, not recruiting, Genentech, Inc. | Recruiting --> Active, not recruiting
    Enrollment closed • Combination therapy • Metastases
    |
    EGFR (Epidermal growth factor receptor) • BRAF (B-raf proto-oncogene) • ALK (Anaplastic lymphoma kinase)
    |
    Tecentriq (atezolizumab) • migoprotafib (RLY-1971)
    2years
    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, Recruiting, Genentech, Inc. | Phase classification: P1a/1b --> P1
    Phase classification • Combination therapy • Metastases
    |
    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)
    2years
    Identification of GDC-1971 (RLY-1971), a SHP2 Inhibitor Designed for the Treatment of Solid Tumors. (PubMed, J Med Chem)
    We were drawn to the pharmacological potential of SHP2 inhibition, especially following the initial observation that drug-like compounds could bind an allosteric site and enforce a closed, inactive state of the enzyme. Here, we describe the identification and characterization of GDC-1971 (formerly RLY-1971), a SHP2 inhibitor currently in clinical trials in combination with KRAS G12C inhibitor divarasib (GDC-6036) for the treatment of solid tumors driven by a KRAS G12C mutation.
    Journal
    |
    KRAS (KRAS proto-oncogene GTPase)
    |
    KRAS mutation
    |
    divarasib (RG6330) • migoprotafib (RLY-1971)