^
    10d
    KANDLELIT-001: A Study of Calderasib (MK-1084) in KRAS Mutant Advanced Solid Tumors (MK-1084-001) (clinicaltrials.gov)
    P1, N=167, Recruiting, Merck Sharp & Dohme LLC | N=126 --> 167
    Enrollment change
    |
    PD-L1 (Programmed death ligand 1) • KRAS (KRAS proto-oncogene GTPase)
    |
    KRAS mutation • KRAS G12C • KRAS G12
    |
    Keytruda (pembrolizumab) • Erbitux (cetuximab) • carboplatin • 5-fluorouracil • pemetrexed • oxaliplatin • leucovorin calcium • calderasib (MK-1084)
    14d
    From KRASG12D to Pan-KRAS Inhibitors─A Journey Enabled by Synthetic Innovation and Structure-Based Drug Design. (PubMed, J Med Chem)
    KRAS, a significant oncology target, has been challenging to develop drugs for until recent discoveries of KRASG12C mutant-specific covalent inhibitors, including MK-1084. This article describes efforts toward the discovery of KRASG12D mutant-specific inhibitors and how synthetic innovations and structure-based drug design were utilized to facilitate the discovery of pan-KRAS inhibitors.
    Journal
    |
    KRAS (KRAS proto-oncogene GTPase)
    |
    KRAS mutation • KRAS G12C • KRAS G12D
    |
    calderasib (MK-1084)
    21d
    KANDLELIT-013: MK-3475A±MK-1084 in Completely Resected Stage IIA-IIIB (N2) KRAS G12Cm NSCLC (MK-1084-013) (clinicaltrials.gov)
    P3, N=400, Recruiting, Merck Sharp & Dohme LLC | Not yet recruiting --> Recruiting
    Enrollment open
    |
    KRAS (KRAS proto-oncogene GTPase)
    |
    KRAS mutation • KRAS G12C • KRAS G12
    |
    Keytruda (pembrolizumab) • calderasib (MK-1084)
    22d
    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
    Trial initiation date
    |
    KRAS (KRAS proto-oncogene GTPase)
    |
    KRAS mutation • KRAS G12C • KRAS G12
    |
    Keytruda (pembrolizumab) • Erbitux (cetuximab) • carboplatin • pemetrexed • calderasib (MK-1084)
    1m
    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 | N=57 --> 190
    Enrollment change • Trial initiation 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)
    1m
    A Clinical Study of Calderasib (MK-1084) and Other Treatments for Participants With Non-Small Cell Lung Cancer (MK-1084-007/KANDLELIT-007) (clinicaltrials.gov)
    P3, N=675, Recruiting, Merck Sharp & Dohme LLC | N=218 --> 675
    Enrollment change • Trial initiation date
    |
    PD-L1 (Programmed death ligand 1) • KRAS (KRAS proto-oncogene GTPase)
    |
    Keytruda (pembrolizumab) • cisplatin • carboplatin • pemetrexed • calderasib (MK-1084)
    1m
    A Clinical Study of MK-1084 With Other Treatments for Non-small Cell Lung Cancer (MK-3475-01F) (clinicaltrials.gov)
    P1/2, N=57, Recruiting, Merck Sharp & Dohme LLC | N=32 --> 57
    Enrollment change
    |
    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)
    1m
    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 | N=32 --> 190
    Enrollment change • Trial initiation 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)
    1m
    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 | N=43 --> 130
    Enrollment change • Trial initiation date
    |
    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=32, Recruiting, Merck Sharp & Dohme LLC
    New P1/2 trial
    |
    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)
    2ms
    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)
    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=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)