^
    2d
    A Systematic Review of the Efficacy of KRAS p.G12C Inhibitors in Metastatic Colorectal Cancer: The Current State of Science. (PubMed, Cancer Invest)
    Adagrasib monotherapy yielded a median PFS of 4.4-5.6 months, an OS of 10-19.8 months, and an ORR of 19-23%, while its combination with cetuximab reported a PFS of 6.9 months, an OS of 13.4-15.9 months and an ORR of 34-46%...When combined with panitumumab, 960 mg sotorasib demonstrated better results with a PFS of 5.6-5.7 months, OS of 15.2 months and an ORR of 12.5-30%. Similarly, divarasib monotherapy led to a PFS of 5.6-6.9 months and an ORR of 20%, while its combination with cetuximab resulted in a PFS of 8.1 months and an ORR of 62.5%. Combination therapy of olomorasib and MK-1084, which are new-generation KRAS p.G12C (c.34G > T) inhibitors, with cetuximab also demonstrated highly promising efficacy with ORR of 38-44% and 50%, respectively...Initial results of KRAS-G12C inhibitors appear highly promising when they are combined with anti-EGFR therapy compared to historical therapeutic agents indicated for patients with chemotherapy-refractory CRC. Encouraging benefits warrant frontline trials with these novel therapeutics.
    Journal
    |
    KRAS (KRAS proto-oncogene GTPase)
    |
    KRAS mutation • KRAS G12C • KRAS G12
    |
    Erbitux (cetuximab) • Vectibix (panitumumab) • Lumakras (sotorasib) • Krazati (adagrasib) • divarasib (RG6330) • calderasib (MK-1084) • olomorasib (LY3537982)
    3d
    KEYMAKER-U01 Substudy 01J: A Study of Pembrolizumab Plus MK-1084 in Participants With Non-Small Cell Lung Cancer (NSCLC) With Kirsten Rat Sarcoma Viral Oncogene Homolog (KRAS) G12C Mutations (MK-3475-01J/KEYMAKER-U01J) (clinicaltrials.gov)
    P2, N=43, Recruiting, Merck Sharp & Dohme LLC | Not yet recruiting --> Recruiting | N=24 --> 43
    Enrollment open • Enrollment change
    |
    KRAS (KRAS proto-oncogene GTPase)
    |
    KRAS mutation • KRAS G12C • KRAS G12
    |
    Keytruda (pembrolizumab) • Erbitux (cetuximab) • carboplatin • pemetrexed • calderasib (MK-1084)
    7d
    A Clinical Study of MK-1084 With Other Treatments for Non-small Cell Lung Cancer (MK-3475-01F) (clinicaltrials.gov)
    P1/2, N=190, Recruiting, Merck Sharp & Dohme LLC | Not yet recruiting --> Recruiting | Trial completion date: Jul 2036 --> May 2037
    Enrollment open • Trial completion date
    |
    PD-L1 (Programmed death ligand 1) • KRAS (KRAS proto-oncogene GTPase)
    |
    KRAS mutation • KRAS G12C • KRAS G12
    |
    Keytruda (pembrolizumab) • Erbitux (cetuximab) • patritumab deruxtecan (U3-1402) • Jiataile (sacituzumab tirumotecan) • calderasib (MK-1084)
    9d
    KANDLELIT-013: MK-3475A±MK-1084 in Completely Resected Stage IIA-IIIB (N2) KRAS G12Cm NSCLC (MK-1084-013) (clinicaltrials.gov)
    P3, N=400, Not yet recruiting, Merck Sharp & Dohme LLC
    New P3 trial
    |
    KRAS (KRAS proto-oncogene GTPase)
    |
    KRAS mutation • KRAS G12C • KRAS G12
    |
    Keytruda (pembrolizumab) • calderasib (MK-1084)
    10d
    A clinical study of new treatments for non-small cell lung cancer (MK-3475-01J) (2025-521939-36-00)
    P1/2, N=15, Not yet recruiting, Merck Sharp & Dohme LLC
    New P1/2 trial
    |
    KRAS (KRAS proto-oncogene GTPase)
    |
    KRAS mutation • KRAS G12C • KRAS G12
    |
    Keytruda (pembrolizumab) • Erbitux (cetuximab) • carboplatin • pemetrexed • calderasib (MK-1084)
    17d
    A clinical study of MK-1084 with targeted therapy and chemotherapy in people with colorectal cancer (MK-1084-012). (2024-517232-22-00)
    P2/3, N=141, Recruiting, Merck Sharp & Dohme LLC
    New P2/3 trial
    |
    KRAS (KRAS proto-oncogene GTPase)
    |
    KRAS mutation • KRAS G12C • KRAS G12
    |
    Avastin (bevacizumab) • Erbitux (cetuximab) • 5-fluorouracil • oxaliplatin • leucovorin calcium • calderasib (MK-1084) • levoleucovorin calcium
    17d
    MK-1084-014: A clinical study of MK-1084 in people with advanced solid tumors (MK 1084-014) (2025-521737-91-00)
    P1/2, N=74, Recruiting, Merck Sharp & Dohme LLC
    New P1/2 trial • Pan tumor
    |
    KRAS (KRAS proto-oncogene GTPase)
    |
    KRAS mutation • KRAS G12C • KRAS G12
    |
    Erbitux (cetuximab) • calderasib (MK-1084)
    17d
    A clinical study of MK-1084 and other treatments for lung cancer (MK-1084-007) (2024-514500-14-00)
    P2/3, N=211, Recruiting, Merck Sharp & Dohme LLC
    New P2/3 trial
    |
    KRAS (KRAS proto-oncogene GTPase)
    |
    Keytruda (pembrolizumab) • cisplatin • carboplatin • pemetrexed • calderasib (MK-1084)
    21d
    A Clinical Study of Calderasib (MK-1084) in Participants With Renal Impairment (MK-1084-010) (clinicaltrials.gov)
    P1, N=34, Completed, Merck Sharp & Dohme LLC | Recruiting --> Completed
    Trial completion
    |
    calderasib (MK-1084)
    2ms
    A Clinical Study of MK-1084 With Rosuvastatin and Metformin in Healthy People (MK-1084-016) (clinicaltrials.gov)
    P1, N=16, Completed, Merck Sharp & Dohme LLC | Active, not recruiting --> Completed
    Trial completion
    |
    metformin • calderasib (MK-1084)
    2ms
    KEYMAKER-U01 Substudy 01J: A Study of Pembrolizumab Plus MK-1084 in Participants With Non-Small Cell Lung Cancer (NSCLC) With Kirsten Rat Sarcoma Viral Oncogene Homolog (KRAS) G12C Mutations (MK-3475-01J/KEYMAKER-U01J) (clinicaltrials.gov)
    P2, N=130, Recruiting, Merck Sharp & Dohme LLC | Not yet recruiting --> Recruiting
    Enrollment open
    |
    KRAS (KRAS proto-oncogene GTPase)
    |
    KRAS mutation • KRAS G12C • KRAS G12
    |
    Keytruda (pembrolizumab) • Erbitux (cetuximab) • carboplatin • pemetrexed • calderasib (MK-1084)
    2ms
    A Clinical Study of MK-1084 With Other Treatments for Non-small Cell Lung Cancer (MK-3475-01F) (clinicaltrials.gov)
    P1/2, N=190, Not yet recruiting, Merck Sharp & Dohme LLC | Trial completion date: Oct 2031 --> Jul 2036
    Trial completion date
    |
    Keytruda (pembrolizumab) • Erbitux (cetuximab) • patritumab deruxtecan (U3-1402) • Jiataile (sacituzumab tirumotecan) • calderasib (MK-1084)