^
    28d
    CodeBreak101: Sotorasib Activity in Subjects With Advanced Solid Tumors With KRAS p.G12C Mutation (CodeBreak 101) (clinicaltrials.gov)
    P1, N=1200, Recruiting, Amgen | Trial completion date: Jun 2029 --> Mar 2028 | Trial primary completion date: Jan 2027 --> Apr 2026
    Trial completion date • Trial primary completion date • Combination therapy • Metastases
    |
    KRAS (KRAS proto-oncogene GTPase)
    |
    KRAS mutation • KRAS G12C • KRAS G12
    |
    Keytruda (pembrolizumab) • Mekinist (trametinib) • Tecentriq (atezolizumab) • Gilotrif (afatinib) • Ibrance (palbociclib) • carboplatin • paclitaxel • docetaxel • everolimus • Vectibix (panitumumab) • Lumakras (sotorasib) • pemetrexed • oxaliplatin • irinotecan • batoprotafib (TNO155) • vociprotafib (RMC-4630) • BI 1701963 • zeluvalimab (AMG 404)
    1m
    CodeBreak101: Sotorasib Activity in Subjects With Advanced Solid Tumors With KRAS p.G12C Mutation (CodeBreak 101) (clinicaltrials.gov)
    P1, N=1200, Recruiting, Amgen | Trial completion date: Mar 2028 --> Jun 2029 | Trial primary completion date: Sep 2025 --> Jan 2027
    Trial completion date • Trial primary completion date • Combination therapy • Metastases
    |
    KRAS (KRAS proto-oncogene GTPase)
    |
    KRAS mutation • KRAS G12C • KRAS G12
    |
    Keytruda (pembrolizumab) • Mekinist (trametinib) • Tecentriq (atezolizumab) • Gilotrif (afatinib) • Ibrance (palbociclib) • carboplatin • paclitaxel • docetaxel • everolimus • Vectibix (panitumumab) • Lumakras (sotorasib) • pemetrexed • oxaliplatin • irinotecan • batoprotafib (TNO155) • vociprotafib (RMC-4630) • BI 1701963 • zeluvalimab (AMG 404)
    4ms
    CodeBreak101: Sotorasib Activity in Subjects With Advanced Solid Tumors With KRAS p.G12C Mutation (CodeBreak 101) (clinicaltrials.gov)
    P1, N=1200, Recruiting, Amgen | Trial primary completion date: Dec 2026 --> Sep 2025
    Trial primary completion date • Combination therapy • Metastases
    |
    KRAS (KRAS proto-oncogene GTPase)
    |
    Keytruda (pembrolizumab) • Avastin (bevacizumab) • Mekinist (trametinib) • Tecentriq (atezolizumab) • Gilotrif (afatinib) • Ibrance (palbociclib) • carboplatin • paclitaxel • docetaxel • everolimus • Vectibix (panitumumab) • Lumakras (sotorasib) • pemetrexed • oxaliplatin • irinotecan • batoprotafib (TNO155) • vociprotafib (RMC-4630) • BI 1701963 • zeluvalimab (AMG 404)
    6ms
    CodeBreak101: Sotorasib Activity in Subjects With Advanced Solid Tumors With KRAS p.G12C Mutation (CodeBreak 101) (clinicaltrials.gov)
    P1, N=1200, Recruiting, Amgen | Phase classification: P1/2 --> P1
    Phase classification • Combination therapy • Metastases
    |
    KRAS (KRAS proto-oncogene GTPase)
    |
    Keytruda (pembrolizumab) • Avastin (bevacizumab) • Mekinist (trametinib) • Tecentriq (atezolizumab) • Gilotrif (afatinib) • Ibrance (palbociclib) • carboplatin • paclitaxel • docetaxel • everolimus • Vectibix (panitumumab) • Lumakras (sotorasib) • pemetrexed • oxaliplatin • irinotecan • batoprotafib (TNO155) • vociprotafib (RMC-4630) • BI 1701963 • zeluvalimab (AMG 404)
    7ms
    Safety and Efficacy Study of SAR442720 in Combination With Other Agents in Advanced Malignancies (clinicaltrials.gov)
    P1/2, N=65, Terminated, Sanofi | Active, not recruiting --> Terminated; Sponsor's decision not related to any safety concern
    Trial termination • Combination therapy • Metastases
    |
    KRAS (KRAS proto-oncogene GTPase) • BRAF (B-raf proto-oncogene) • NF1 (Neurofibromin 1)
    |
    KRAS mutation • KRAS G12C • BRAF mutation • NF1 mutation • KRAS G12 • BRAF amplification
    |
    Keytruda (pembrolizumab) • Krazati (adagrasib) • vociprotafib (RMC-4630)
    7ms
    CodeBreak101: Sotorasib Activity in Subjects With Advanced Solid Tumors With KRAS p.G12C Mutation (CodeBreak 101) (clinicaltrials.gov)
    P1/2, N=1126, Recruiting, Amgen | Trial primary completion date: Sep 2026 --> Dec 2026
    Trial primary completion date • Combination therapy • Metastases
    |
    KRAS (KRAS proto-oncogene GTPase)
    |
    KRAS mutation • KRAS G12C • KRAS G12
    |
    Keytruda (pembrolizumab) • Avastin (bevacizumab) • Mekinist (trametinib) • Tecentriq (atezolizumab) • Gilotrif (afatinib) • Ibrance (palbociclib) • carboplatin • paclitaxel • docetaxel • everolimus • Vectibix (panitumumab) • Lumakras (sotorasib) • pemetrexed • oxaliplatin • irinotecan • batoprotafib (TNO155) • vociprotafib (RMC-4630) • BI 1701963 • zeluvalimab (AMG 404)
    10ms
    Safety and Efficacy Study of SAR442720 in Combination With Other Agents in Advanced Malignancies (clinicaltrials.gov)
    P1/2, N=65, Active, not recruiting, Sanofi | Trial completion date: Jul 2024 --> Mar 2024 | Trial primary completion date: Jul 2024 --> Mar 2024
    Trial completion date • Trial primary completion date • Combination therapy • Metastases
    |
    KRAS (KRAS proto-oncogene GTPase) • BRAF (B-raf proto-oncogene) • NF1 (Neurofibromin 1)
    |
    KRAS mutation • KRAS G12C • BRAF mutation • NF1 mutation • KRAS G12 • BRAF amplification
    |
    Keytruda (pembrolizumab) • Krazati (adagrasib) • vociprotafib (RMC-4630)
    12ms
    CodeBreak101: Sotorasib Activity in Subjects With Advanced Solid Tumors With KRAS p.G12C Mutation (CodeBreak 101) (clinicaltrials.gov)
    P1/2, N=1143, Recruiting, Amgen | Trial primary completion date: Jun 2026 --> Sep 2026
    Trial primary completion date
    |
    KRAS (KRAS proto-oncogene GTPase)
    |
    KRAS mutation • KRAS G12C • KRAS G12
    |
    Keytruda (pembrolizumab) • Avastin (bevacizumab) • Mekinist (trametinib) • Tecentriq (atezolizumab) • Gilotrif (afatinib) • Ibrance (palbociclib) • carboplatin • paclitaxel • docetaxel • 5-fluorouracil • everolimus • Vectibix (panitumumab) • Lumakras (sotorasib) • pemetrexed • oxaliplatin • irinotecan • leucovorin calcium • batoprotafib (TNO155) • vociprotafib (RMC-4630) • BI 1701963 • zeluvalimab (AMG 404)
    12ms
    CodeBreak101: Sotorasib Activity in Subjects With Advanced Solid Tumors With KRAS p.G12C Mutation (CodeBreak 101) (clinicaltrials.gov)
    P1/2, N=1143, Recruiting, Amgen | Phase classification: P1b/2 --> P1/2
    Phase classification
    |
    KRAS (KRAS proto-oncogene GTPase)
    |
    KRAS mutation • KRAS G12C • KRAS G12
    |
    Keytruda (pembrolizumab) • Avastin (bevacizumab) • Mekinist (trametinib) • Tecentriq (atezolizumab) • Gilotrif (afatinib) • Ibrance (palbociclib) • carboplatin • paclitaxel • docetaxel • 5-fluorouracil • everolimus • Vectibix (panitumumab) • Lumakras (sotorasib) • pemetrexed • oxaliplatin • irinotecan • leucovorin calcium • batoprotafib (TNO155) • vociprotafib (RMC-4630) • BI 1701963 • zeluvalimab (AMG 404)
    1year
    CodeBreak101: Sotorasib Activity in Subjects With Advanced Solid Tumors With KRAS p.G12C Mutation (CodeBreak 101) (clinicaltrials.gov)
    P1b/2, N=1143, Recruiting, Amgen | Trial completion date: Jul 2027 --> Oct 2027
    Trial completion date • Combination therapy • Metastases
    |
    KRAS (KRAS proto-oncogene GTPase)
    |
    KRAS mutation • KRAS G12C • KRAS G12
    |
    Keytruda (pembrolizumab) • Avastin (bevacizumab) • Mekinist (trametinib) • Tecentriq (atezolizumab) • Gilotrif (afatinib) • Ibrance (palbociclib) • carboplatin • paclitaxel • docetaxel • 5-fluorouracil • everolimus • Vectibix (panitumumab) • Lumakras (sotorasib) • pemetrexed • oxaliplatin • irinotecan • leucovorin calcium • batoprotafib (TNO155) • vociprotafib (RMC-4630) • BI 1701963 • zeluvalimab (AMG 404)
    1year
    CodeBreak101: Sotorasib Activity in Subjects With Advanced Solid Tumors With KRAS p.G12C Mutation (CodeBreak 101) (clinicaltrials.gov)
    P1b/2, N=1143, Recruiting, Amgen | Trial primary completion date: Jan 2025 --> May 2026
    Trial primary completion date • Combination therapy • Metastases
    |
    KRAS (KRAS proto-oncogene GTPase)
    |
    KRAS mutation • KRAS G12C • KRAS G12
    |
    Keytruda (pembrolizumab) • Avastin (bevacizumab) • Mekinist (trametinib) • Tecentriq (atezolizumab) • Gilotrif (afatinib) • Ibrance (palbociclib) • carboplatin • paclitaxel • docetaxel • 5-fluorouracil • everolimus • Vectibix (panitumumab) • Lumakras (sotorasib) • pemetrexed • oxaliplatin • irinotecan • leucovorin calcium • batoprotafib (TNO155) • vociprotafib (RMC-4630) • BI 1701963 • zeluvalimab (AMG 404)
    over1year
    CodeBreak101: Sotorasib Activity in Subjects With Advanced Solid Tumors With KRAS p.G12C Mutation (CodeBreak 101) (clinicaltrials.gov)
    P1b/2, N=1143, Recruiting, Amgen | Trial completion date: Jan 2029 --> Jul 2027 | Trial primary completion date: Jul 2026 --> Jan 2025
    Trial completion date • Trial primary completion date • Combination therapy • Metastases
    |
    KRAS (KRAS proto-oncogene GTPase)
    |
    KRAS mutation • KRAS G12C • KRAS G12
    |
    Keytruda (pembrolizumab) • Avastin (bevacizumab) • Mekinist (trametinib) • Tecentriq (atezolizumab) • Gilotrif (afatinib) • Ibrance (palbociclib) • carboplatin • paclitaxel • docetaxel • 5-fluorouracil • everolimus • Vectibix (panitumumab) • Lumakras (sotorasib) • pemetrexed • oxaliplatin • irinotecan • leucovorin calcium • batoprotafib (TNO155) • vociprotafib (RMC-4630) • BI 1701963 • zeluvalimab (AMG 404)
    over1year
    Phase I/Ib study of SHP2-ERK inhibition in KRASm pancreatic cancer (SHERPA trial) and preclinical identification of potential resistance markers (ESMO 2023)
    The aim of this phase I/Ib trial is to assess safety and efficacy of treatment with SHP2 inhibitor RMC-4630 and ERK inhibitor LY3214996 in KRASm PDAC, non-small cell lung carcinoma (NSCLC) and colorectal carcinoma (CRC) patients. The RP2D has not been determined yet. Alterations in the PI3K/AKT/mTOR and the c-JUN pathways could be markers for drug resistance, which data are pending.
    P1 data • Preclinical
    |
    KRAS (KRAS proto-oncogene GTPase) • PTEN (Phosphatase and tensin homolog) • JUN (Jun proto-oncogene)
    |
    KRAS mutation
    |
    vociprotafib (RMC-4630) • temuterkib (LY3214996)
    over1year
    Dose-Esc/Exp RMC4630 & Cobi in Relapsed/Refractory Solid Tumors & RMC4630& Osi in EGFR+ Locally Adv/Meta NSCLC (clinicaltrials.gov)
    P1/2, N=113, Completed, Revolution Medicines, Inc. | Phase classification: P1b/2 --> P1/2
    Phase classification
    |
    EGFR (Epidermal growth factor receptor) • KRAS (KRAS proto-oncogene GTPase) • BRAF (B-raf proto-oncogene) • NF1 (Neurofibromin 1)
    |
    KRAS mutation • EGFR mutation • BRAF mutation • NF1 mutation • BRAF amplification
    |
    Tagrisso (osimertinib) • Cotellic (cobimetinib) • vociprotafib (RMC-4630)
    over1year
    RMC-4630-03: Combination Study of RMC-4630 and Sotorasib for NSCLC Subjects With KRASG12C Mutation After Failure of Prior Standard Therapies (clinicaltrials.gov)
    P2, N=47, Active, not recruiting, Revolution Medicines, Inc. | Recruiting --> Active, not recruiting | Trial primary completion date: Mar 2023 --> Sep 2023
    Enrollment closed • Trial primary completion date
    |
    KRAS (KRAS proto-oncogene GTPase)
    |
    Lumakras (sotorasib) • vociprotafib (RMC-4630)
    over1year
    CodeBreak101: Sotorasib Activity in Subjects With Advanced Solid Tumors With KRAS p.G12C Mutation (CodeBreak 101) (clinicaltrials.gov)
    P1b/2, N=1143, Recruiting, Amgen | Trial completion date: Apr 2028 --> Jan 2029 | Trial primary completion date: Feb 2026 --> Jul 2026
    Trial completion date • Trial primary completion date • Combination therapy • Metastases
    |
    KRAS (KRAS proto-oncogene GTPase)
    |
    KRAS mutation • KRAS G12C • KRAS G12
    |
    Keytruda (pembrolizumab) • Avastin (bevacizumab) • Mekinist (trametinib) • Tecentriq (atezolizumab) • Gilotrif (afatinib) • Ibrance (palbociclib) • carboplatin • paclitaxel • docetaxel • 5-fluorouracil • everolimus • Vectibix (panitumumab) • Lumakras (sotorasib) • pemetrexed • oxaliplatin • irinotecan • leucovorin calcium • batoprotafib (TNO155) • vociprotafib (RMC-4630) • BI 1701963 • zeluvalimab (AMG 404)
    over1year
    A next-generation KRASG12C inhibitor ABSK071 demonstrated broad synergy with other therapeutic agents in KRASG12C mutated cancer models (AACR 2023)
    A set of immuno-oncology reagents, including anti-PD-1/L1, CSF-1R inhibitor (ABSK021) and CD73 inhibitor (ABSK051) were also tested in combination with ABSK071 in vivo using mouse syngeneic models. ABSK071 demonstrated much stronger inhibitory activity than sotorasib and adagrasib against a variety of cell lines harboring KRASG12C, as well as significantly better in vivo anti-tumor efficacy in xenograft models that were less sensitive to sotorasib. Synergistic effects on cell growth inhibition were observed in vitro with ABSK071 in combination with several agents including cetuximab, afatinib, AZD4547, TNO-155, RMC-4630 and BI3406... ABSK071 is a next-generation KRASG12C inhibitor with greater activity and anti-tumor efficacy in vitro and in vivo. It also demonstrated broad synergistic effects with a large set of targeted agents and immuno-oncology agents, indicating its strong potential in combinatory therapy in treating a wider range of KRASG12C-dependent cancers.
    Preclinical • Late-breaking abstract • PD(L)-1 Biomarker • IO biomarker
    |
    KRAS (KRAS proto-oncogene GTPase)
    |
    KRAS mutation
    |
    Erbitux (cetuximab) • Gilotrif (afatinib) • Lumakras (sotorasib) • Krazati (adagrasib) • fexagratinib (ABSK091) • BI-3406 • batoprotafib (TNO155) • vociprotafib (RMC-4630) • ABSK071 • pimicotinib (ABSK021) • ABSK051
    over1year
    Safety and Efficacy Study of SAR442720 in Combination With Other Agents in Advanced Malignancies (clinicaltrials.gov)
    P1/2, N=65, Active, not recruiting, Sanofi | Recruiting --> Active, not recruiting | N=133 --> 65 | Trial completion date: Jan 2025 --> Jul 2024 | Trial primary completion date: Jan 2025 --> Jul 2024
    Enrollment closed • Enrollment change • Trial completion date • Trial primary completion date • Combination therapy • Metastases
    |
    KRAS (KRAS proto-oncogene GTPase) • BRAF (B-raf proto-oncogene) • NF1 (Neurofibromin 1)
    |
    KRAS mutation • KRAS G12C • BRAF mutation • NF1 mutation • KRAS G12 • BRAF amplification
    |
    Keytruda (pembrolizumab) • Krazati (adagrasib) • vociprotafib (RMC-4630)
    almost2years
    CodeBreak101: Sotorasib Activity in Subjects With Advanced Solid Tumors With KRAS p.G12C Mutation (CodeBreak 101) (clinicaltrials.gov)
    P1b/2, N=1143, Recruiting, Amgen | Trial completion date: Jun 2027 --> Apr 2028 | Trial primary completion date: Dec 2024 --> Feb 2026
    Trial completion date • Trial primary completion date • Combination therapy • Metastases
    |
    KRAS (KRAS proto-oncogene GTPase)
    |
    KRAS mutation • KRAS G12C • KRAS G12
    |
    Keytruda (pembrolizumab) • Avastin (bevacizumab) • Mekinist (trametinib) • Tecentriq (atezolizumab) • Gilotrif (afatinib) • Ibrance (palbociclib) • carboplatin • paclitaxel • docetaxel • 5-fluorouracil • everolimus • Vectibix (panitumumab) • Lumakras (sotorasib) • pemetrexed • oxaliplatin • irinotecan • leucovorin calcium • batoprotafib (TNO155) • vociprotafib (RMC-4630) • BI 1701963 • zeluvalimab (AMG 404)
    almost2years
    CodeBreak101: Sotorasib Activity in Subjects With Advanced Solid Tumors With KRAS p.G12C Mutation (CodeBreak 101) (clinicaltrials.gov)
    P1b/2, N=1143, Recruiting, Amgen | Trial completion date: Oct 2026 --> Jun 2027 | Trial primary completion date: Aug 2024 --> Dec 2024
    Trial completion date • Trial primary completion date • Combination therapy • Metastases
    |
    KRAS (KRAS proto-oncogene GTPase)
    |
    KRAS mutation • KRAS G12C • KRAS G12
    |
    Keytruda (pembrolizumab) • Avastin (bevacizumab) • Mekinist (trametinib) • Tecentriq (atezolizumab) • Gilotrif (afatinib) • Ibrance (palbociclib) • carboplatin • paclitaxel • docetaxel • 5-fluorouracil • everolimus • Vectibix (panitumumab) • Lumakras (sotorasib) • pemetrexed • oxaliplatin • irinotecan • leucovorin calcium • batoprotafib (TNO155) • vociprotafib (RMC-4630) • BI 1701963 • zeluvalimab (AMG 404)
    almost2years
    Safety and Efficacy Study of SAR442720 in Combination With Other Agents in Advanced Malignancies (clinicaltrials.gov)
    P1/2, N=133, Recruiting, Sanofi | Trial completion date: Dec 2025 --> Dec 2024 | Trial primary completion date: Dec 2025 --> Dec 2024
    Trial completion date • Trial primary completion date • Combination therapy • Metastases
    |
    KRAS (KRAS proto-oncogene GTPase) • BRAF (B-raf proto-oncogene) • NF1 (Neurofibromin 1)
    |
    KRAS mutation • KRAS G12C • BRAF mutation • NF1 mutation • KRAS G12 • BRAF amplification
    |
    Keytruda (pembrolizumab) • Krazati (adagrasib) • vociprotafib (RMC-4630)
    almost2years
    Safety and Efficacy Study of SAR442720 in Combination With Other Agents in Advanced Malignancies (clinicaltrials.gov)
    P1/2, N=133, Recruiting, Sanofi | Trial completion date: Jul 2025 --> Dec 2025 | Trial primary completion date: Jul 2025 --> Dec 2025
    Trial completion date • Trial primary completion date • Combination therapy • Metastases
    |
    KRAS (KRAS proto-oncogene GTPase) • BRAF (B-raf proto-oncogene) • NF1 (Neurofibromin 1)
    |
    KRAS mutation • KRAS G12C • BRAF mutation • NF1 mutation • KRAS G12 • BRAF amplification
    |
    Keytruda (pembrolizumab) • Krazati (adagrasib) • vociprotafib (RMC-4630)
    2years
    Dose Escalation of RMC-4630 Monotherapy in Relapsed/Refractory Solid Tumors (clinicaltrials.gov)
    P1, N=133, Active, not recruiting, Revolution Medicines, Inc. | Recruiting --> Active, not recruiting | Trial completion date: Nov 2022 --> May 2023 | Trial primary completion date: Jul 2022 --> Mar 2023
    Enrollment closed • Trial completion date • Trial primary completion date
    |
    KRAS (KRAS proto-oncogene GTPase) • BRAF (B-raf proto-oncogene) • NF1 (Neurofibromin 1)
    |
    KRAS G12C • BRAF mutation • KRAS G12 • KRAS amplification • BRAF amplification
    |
    vociprotafib (RMC-4630)
    2years
    Dose-Escalation/Expansion of RMC-4630 and Cobimetinib in Relapsed/Refractory Solid Tumors and RMC-4630 and Osimertinib in EGFR Positive Locally Advanced/Metastatic NSCLC (clinicaltrials.gov)
    P1b/2, N=113, Completed, Revolution Medicines, Inc. | Active, not recruiting --> Completed | N=168 --> 113
    Trial completion • Enrollment change
    |
    EGFR (Epidermal growth factor receptor) • KRAS (KRAS proto-oncogene GTPase) • BRAF (B-raf proto-oncogene) • NF1 (Neurofibromin 1)
    |
    KRAS mutation • EGFR mutation • BRAF mutation • NF1 mutation • BRAF amplification
    |
    Tagrisso (osimertinib) • Cotellic (cobimetinib) • vociprotafib (RMC-4630)
    over2years
    RMC-4630, a SHP2 Inhibitor, in Combination with Sotorasib for Advanced KRASG12C NSCLC After Failure of Prior Standard Therapies: A Phase 2 Trial (IASLC-WCLC 2022)
    Emerging clinical data from sotorasib and adagrasib monotherapy studies in KRASG12C NSCLC has revealed heterogeneity in the response of subpopulations defined by co-mutations in associated targets such as KEAP1 and STK11. This trial is currently enrolling in the United States and additional sites will also be open in Europe, UK, Australia, and Asia in 2022. The first patient was enrolled at the end of 2021 and enrollment is ongoing.
    P2 data • Combination therapy
    |
    KRAS (KRAS proto-oncogene GTPase) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • STK11 (Serine/threonine kinase 11) • KEAP1 (Kelch Like ECH Associated Protein 1)
    |
    KRAS mutation • KRAS G12C • STK11 mutation • KRAS G12
    |
    Lumakras (sotorasib) • Krazati (adagrasib) • vociprotafib (RMC-4630)
    over2years
    Sotorasib in Combination with RMC-4630, a SHP2 Inhibitor, in KRAS p.G12C-Mutated NSCLC and Other Solid Tumors (IASLC-WCLC 2022)
    As of January 17, 2022, 21 patients (11-NSCLC, 6-CRC, and 4-other solid tumors) who had received a median of 2 prior lines of therapy (range, 1-6) were enrolled; 10 patients (48%) had received prior KRASG12C inhibitor therapy (8-sotorasib, 2-adagrasib). The combination of sotorasib with RMC-4630 was safe and tolerable in patients with KRAS p.G12C-mutated solid tumors. Promising clinical activity was observed in KRAS p.G12C-mutated NSCLC patients, most notably in those KRASG12C inhibitor-naïve. Dose expansion is underway to further define efficacy and safety in both KRASG12C inhibitor-naïve and KRASG12C inhibitor-exposed NSCLC patients.
    Combination therapy
    |
    KRAS (KRAS proto-oncogene GTPase)
    |
    KRAS mutation • KRAS G12C • KRAS G12
    |
    Lumakras (sotorasib) • Krazati (adagrasib) • vociprotafib (RMC-4630)
    over2years
    SHERPA: Combination Therapy of RMC-4630 and LY3214996 in Metastatic KRAS Mutant Cancers (clinicaltrials.gov)
    P1, N=55, Recruiting, The Netherlands Cancer Institute | Not yet recruiting --> Recruiting
    Enrollment open • Combination therapy
    |
    EGFR (Epidermal growth factor receptor) • KRAS (KRAS proto-oncogene GTPase) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • MET (MET proto-oncogene, receptor tyrosine kinase) • PTEN (Phosphatase and tensin homolog) • HRAS (Harvey rat sarcoma viral oncogene homolog)
    |
    vociprotafib (RMC-4630) • temuterkib (LY3214996)
    over2years
    Safety and Efficacy Study of SAR442720 in Combination With Other Agents in Advanced Malignancies (clinicaltrials.gov)
    P1/2, N=133, Recruiting, Sanofi | Trial primary completion date: Nov 2024 --> Jul 2025 | Trial completion date: Nov 2024 --> Jul 2025
    Trial completion date • Trial primary completion date
    |
    KRAS (KRAS proto-oncogene GTPase) • BRAF (B-raf proto-oncogene) • NF1 (Neurofibromin 1)
    |
    KRAS mutation • KRAS G12C • BRAF mutation • NF1 mutation • KRAS G12 • BRAF amplification
    |
    Keytruda (pembrolizumab) • Krazati (adagrasib) • vociprotafib (RMC-4630)
    over2years
    Safety and Efficacy Study of SAR442720 in Combination With Other Agents in Advanced Malignancies (clinicaltrials.gov)
    P1/2, N=133, Recruiting, Sanofi | Trial completion date: Jul 2025 --> Nov 2024 | Trial primary completion date: Jul 2025 --> Nov 2024
    Trial completion date • Trial primary completion date • Combination therapy
    |
    KRAS (KRAS proto-oncogene GTPase) • BRAF (B-raf proto-oncogene) • NF1 (Neurofibromin 1)
    |
    KRAS mutation • KRAS G12C • BRAF mutation • NF1 mutation • KRAS G12 • BRAF amplification
    |
    Keytruda (pembrolizumab) • Krazati (adagrasib) • vociprotafib (RMC-4630)
    over2years
    CodeBreak101: Sotorasib Activity in Subjects With Advanced Solid Tumors With KRAS p.G12C Mutation (CodeBreak 101) (clinicaltrials.gov)
    P1b/2, N=1054, Recruiting, Amgen | Trial completion date: Jan 2027 --> Aug 2026 | Trial primary completion date: Jan 2024 --> Aug 2024
    Trial completion date • Trial primary completion date • Combination therapy
    |
    KRAS (KRAS proto-oncogene GTPase)
    |
    KRAS mutation • KRAS G12C • KRAS G12
    |
    Keytruda (pembrolizumab) • Avastin (bevacizumab) • Mekinist (trametinib) • Tecentriq (atezolizumab) • Gilotrif (afatinib) • Ibrance (palbociclib) • carboplatin • docetaxel • 5-fluorouracil • everolimus • Vectibix (panitumumab) • Lumakras (sotorasib) • pemetrexed • oxaliplatin • irinotecan • leucovorin calcium • batoprotafib (TNO155) • vociprotafib (RMC-4630) • zeluvalimab (AMG 404)
    over2years
    Safety and Efficacy Study of SAR442720 in Combination With Other Agents in Advanced Malignancies (clinicaltrials.gov)
    P1/2, N=133, Recruiting, Sanofi | N=88 --> 133
    Enrollment change • Combination therapy
    |
    KRAS (KRAS proto-oncogene GTPase) • BRAF (B-raf proto-oncogene) • NF1 (Neurofibromin 1)
    |
    KRAS mutation • KRAS G12C • BRAF mutation • NF1 mutation • KRAS G12 • BRAF amplification
    |
    Keytruda (pembrolizumab) • Krazati (adagrasib) • vociprotafib (RMC-4630)
    over2years
    RMC-4630 and sotorasib for advanced KRASG12C NSCLC after failure of prior standard therapies: A phase II trial (ELCC 2022)
    Emerging clinical data from sotorasib and adagrasib monotherapy studies in KRASG12C NSCLC reveal heterogeneity in the response of subpopulations defined by co-mutations in associated targets such as KEAP1 and STK11. Secondary endpoints include DOR, DCR, PFS, OS, safety/tolerability, and PK of RMC-4630 in combination with sotorasib. This trial is currently enrolling in the United States and will also be open at sites in Europe, UK, Australia, and Asia.
    P2 data
    |
    KRAS (KRAS proto-oncogene GTPase) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • STK11 (Serine/threonine kinase 11) • KEAP1 (Kelch Like ECH Associated Protein 1)
    |
    KRAS mutation • KRAS G12C • STK11 mutation • KRAS G12
    |
    Lumakras (sotorasib) • Krazati (adagrasib) • vociprotafib (RMC-4630)
    almost3years
    SHERPA: Combination Therapy of RMC-4630 and LY3214996 in Metastatic KRAS Mutant Cancers (clinicaltrials.gov)
    P1, N=55, Not yet recruiting, The Netherlands Cancer Institute | Trial completion date: Oct 2023 --> Jul 2024 | Initiation date: Oct 2021 --> Feb 2022 | Trial primary completion date: Oct 2023 --> Jan 2024
    Trial completion date • Trial initiation date • Trial primary completion date • Combination therapy
    |
    EGFR (Epidermal growth factor receptor) • KRAS (KRAS proto-oncogene GTPase) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • MET (MET proto-oncogene, receptor tyrosine kinase) • PTEN (Phosphatase and tensin homolog) • HRAS (Harvey rat sarcoma viral oncogene homolog)
    |
    vociprotafib (RMC-4630) • temuterkib (LY3214996)
    almost3years
    Dose Escalation of RMC-4630 Monotherapy in Relapsed/Refractory Solid Tumors (clinicaltrials.gov)
    P1, N=175, Recruiting, Revolution Medicines, Inc. | Trial completion date: Oct 2021 --> Nov 2022 | Trial primary completion date: Oct 2021 --> Jul 2022
    Trial completion date • Trial primary completion date
    |
    KRAS (KRAS proto-oncogene GTPase) • BRAF (B-raf proto-oncogene) • NF1 (Neurofibromin 1)
    |
    KRAS G12C • BRAF mutation • KRAS G12 • KRAS amplification • BRAF amplification
    |
    vociprotafib (RMC-4630)
    almost3years
    CodeBreak101: Sotorasib Activity in Subjects With Advanced Solid Tumors With KRAS p.G12C Mutation (CodeBreak 101) (clinicaltrials.gov)
    P1b/2, N=1280, Recruiting, Amgen | Trial completion date: Jan 2026 --> Jan 2027
    Trial completion date • Combination therapy
    |
    KRAS (KRAS proto-oncogene GTPase)
    |
    KRAS mutation • KRAS G12C • KRAS G12
    |
    Keytruda (pembrolizumab) • Avastin (bevacizumab) • Mekinist (trametinib) • Tecentriq (atezolizumab) • Gilotrif (afatinib) • Ibrance (palbociclib) • carboplatin • docetaxel • 5-fluorouracil • everolimus • Vectibix (panitumumab) • Lumakras (sotorasib) • pemetrexed • oxaliplatin • irinotecan • leucovorin calcium • batoprotafib (TNO155) • vociprotafib (RMC-4630) • zeluvalimab (AMG 404)
    3years
    Combination Study of RMC-4630 and Sotorasib for NSCLC Subjects With KRASG12C Mutation After Failure of Prior Standard Therapies (clinicaltrials.gov)
    P2, N=46, Recruiting, Revolution Medicines, Inc. | Not yet recruiting --> Recruiting
    Clinical • Enrollment open
    |
    KRAS (KRAS proto-oncogene GTPase)
    |
    Lumakras (sotorasib) • vociprotafib (RMC-4630)
    3years
    Combination Study of RMC-4630 and Sotorasib for NSCLC Subjects With KRASG12C Mutation After Failure of Prior Standard Therapies (clinicaltrials.gov)
    P2, N=46, Not yet recruiting, Revolution Medicines, Inc.
    Clinical • New P2 trial
    |
    KRAS (KRAS proto-oncogene GTPase)
    |
    Lumakras (sotorasib) • vociprotafib (RMC-4630)
    3years
    Safety and Efficacy Study of SAR442720 in Combination With Pembrolizumab in Advanced Malignancies (clinicaltrials.gov)
    P1/2, N=88, Recruiting, Sanofi | Trial completion date: May 2024 --> Jul 2025 | Trial primary completion date: May 2024 --> Jul 2025
    Clinical • Trial completion date • Trial primary completion date • Combination therapy
    |
    KRAS (KRAS proto-oncogene GTPase) • BRAF (B-raf proto-oncogene) • NF1 (Neurofibromin 1)
    |
    KRAS mutation • BRAF mutation • NF1 mutation • BRAF amplification
    |
    Keytruda (pembrolizumab) • vociprotafib (RMC-4630)
    3years
    Dose-Escalation/Expansion of RMC-4630 and Cobimetinib in Relapsed/Refractory Solid Tumors and RMC-4630 and Osimertinib in EGFR Positive Locally Advanced/Metastatic NSCLC (clinicaltrials.gov)
    P1b/2, N=168, Active, not recruiting, Revolution Medicines, Inc. | Recruiting --> Active, not recruiting
    Clinical • Enrollment closed
    |
    EGFR (Epidermal growth factor receptor) • KRAS (KRAS proto-oncogene GTPase) • BRAF (B-raf proto-oncogene) • NF1 (Neurofibromin 1)
    |
    KRAS mutation • EGFR mutation • BRAF mutation • NF1 mutation • BRAF amplification
    |
    Tagrisso (osimertinib) • Cotellic (cobimetinib) • vociprotafib (RMC-4630)
    3years
    CodeBreak101: Sotorasib Activity in Subjects With Advanced Solid Tumors With KRAS p.G12C Mutation (CodeBreak 101) (clinicaltrials.gov)
    P1b/2, N=1113, Recruiting, Amgen | Trial completion date: Feb 2028 --> Oct 2025
    Clinical • Trial completion date • Combination therapy
    |
    KRAS (KRAS proto-oncogene GTPase)
    |
    KRAS mutation • KRAS G12C • KRAS G12
    |
    Keytruda (pembrolizumab) • Avastin (bevacizumab) • Mekinist (trametinib) • Tecentriq (atezolizumab) • Gilotrif (afatinib) • Ibrance (palbociclib) • carboplatin • docetaxel • 5-fluorouracil • everolimus • Vectibix (panitumumab) • Lumakras (sotorasib) • pemetrexed • oxaliplatin • irinotecan • leucovorin calcium • batoprotafib (TNO155) • vociprotafib (RMC-4630) • zeluvalimab (AMG 404)
    over3years
    [VIRTUAL] Next generation sequencing reveals the genetic landscape of PTPN11 in Chinese lung cancer patients (ESMO 2021)
    Several SHP2 allosteric inhibitors, such as ICP-189 and RMC-4630, have been entered into clinical trials. The mutational characteristics of PTPN11 in Chinese lung cancer population was first revealed in this study, which provides a broad range of scenarios for the future clinical application of SHP2 inhibitors in lung cancer.
    Clinical • Next-generation sequencing
    |
    EGFR (Epidermal growth factor receptor) • HER-2 (Human epidermal growth factor receptor 2) • KRAS (KRAS proto-oncogene GTPase) • BRAF (B-raf proto-oncogene) • ALK (Anaplastic lymphoma kinase) • ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS) • FGFR1 (Fibroblast growth factor receptor 1) • MAP2K1 (Mitogen-activated protein kinase kinase 1) • PTPN11 (Protein Tyrosine Phosphatase Non-Receptor Type 11) • NTRK (Neurotrophic receptor tyrosine kinase)
    |
    ROS1 fusion • NTRK fusion
    |
    vociprotafib (RMC-4630) • ICP-189
    over3years
    Safety and Efficacy Study of SAR442720 in Combination With Pembrolizumab in Advanced Malignancies (clinicaltrials.gov)
    P1/2, N=88, Recruiting, Sanofi | Phase classification: P1 --> P1/2 | N=24 --> 88
    Clinical • Phase classification • Enrollment change • Combination therapy
    |
    KRAS (KRAS proto-oncogene GTPase) • BRAF (B-raf proto-oncogene) • NF1 (Neurofibromin 1)
    |
    KRAS mutation • BRAF mutation • NF1 mutation • BRAF amplification
    |
    Keytruda (pembrolizumab) • vociprotafib (RMC-4630)