^
    16d
    A Study of the Effect of Itraconazole and Phenytoin on MK-1084 in Healthy Adults (MK-1084-008) (clinicaltrials.gov)
    P1, N=28, Completed, Merck Sharp & Dohme LLC
    New P1 trial
    |
    MK-1084 • itraconazole
    1m
    A Study of MK-1084 Human Absorption, Distribution, Metabolism, and Excretion in Healthy Adult Participants (MK-1084-006) (clinicaltrials.gov)
    P1, N=8, Completed, Merck Sharp & Dohme LLC
    New P1 trial
    |
    MK-1084
    1m
    CA43815: A Study of MK-1084 With Midazolam and Digoxin in Healthy Participants (MK-1084-009) (clinicaltrials.gov)
    P1, N=28, Completed, Merck Sharp & Dohme LLC | Active, not recruiting --> Completed
    Trial completion
    |
    MK-1084 • midazolam hydrochloride
    2ms
    A Study of MK-1084 in KRAS Mutant Advanced Solid Tumors (MK-1084-001) (clinicaltrials.gov)
    P1, N=830, Recruiting, Merck Sharp & Dohme LLC | Trial completion date: Aug 2026 --> Aug 2027 | Trial primary completion date: Aug 2026 --> Aug 2027
    Trial completion date • Trial primary completion date • Combination therapy • Metastases
    |
    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 • MK-1084
    3ms
    A Study to Evaluate the Effect of Food, Formulation, and a Proton Pump Inhibitor (PPI) on MK-1084 in Healthy Adult Participants (MK-1084-003) (clinicaltrials.gov)
    P1, N=56, Completed, Merck Sharp & Dohme LLC
    New P1 trial
    |
    MK-1084
    3ms
    CA43815: A Study of MK-1084 With Midazolam and Digoxin in Healthy Participants (MK-1084-009) (clinicaltrials.gov)
    P1, N=28, Active, not recruiting, Merck Sharp & Dohme LLC | Recruiting --> Active, not recruiting
    Enrollment closed
    |
    MK-1084 • midazolam hydrochloride
    3ms
    CA43815: A Study of MK-1084 With Midazolam and Digoxin in Healthy Participants (MK-1084-009) (clinicaltrials.gov)
    P1, N=28, Recruiting, Merck Sharp & Dohme LLC | Not yet recruiting --> Recruiting
    Enrollment open
    |
    MK-1084 • midazolam hydrochloride
    4ms
    A Study of MK-1084 With Midazolam and Digoxin in Healthy Participants (MK-1084-009) (clinicaltrials.gov)
    P1, N=28, Not yet recruiting, Merck Sharp & Dohme LLC
    New P1 trial
    |
    MK-1084 • midazolam hydrochloride
    6ms
    Discovery of MK-1084: An Orally Bioavailable and Low-Dose KRASG12C Inhibitor. (PubMed, J Med Chem)
    Herein, we disclose our journey toward the discovery of MK-1084, an orally bioavailable and low-dose KRASG12C covalent inhibitor currently in phase I clinical trials (NCT05067283). We leveraged structure-based drug design to identify a macrocyclic core structure, and hypothesis-driven optimization of biopharmaceutical properties to further improve metabolic stability and tolerability.
    Journal
    |
    KRAS (KRAS proto-oncogene GTPase)
    |
    MK-1084
    7ms
    Study of MK-0472 in Participants With Advanced/Metastatic Solid Tumors (MK-0472-001) (clinicaltrials.gov)
    P1, N=178, Recruiting, Merck Sharp & Dohme LLC | N=100 --> 178
    Enrollment change
    |
    Keytruda (pembrolizumab) • MK-1084 • MK-0472
    8ms
    A Study of MK-1084 Plus Pembrolizumab (MK-3475) in Participants With KRAS G12C Mutant, Metastatic Non-small Cell Lung Cancer (NSCLC) With Programmed Cell Death Ligand 1 (PD-L1) Tumor Proportion Score (TPS) ≥50% (MK-1084-004) (clinicaltrials.gov)
    P3, N=600, Recruiting, Merck Sharp & Dohme LLC | Not yet recruiting --> Recruiting
    Enrollment open • Combination therapy • Tumor proportion score • IO biomarker • Metastases
    |
    KRAS (KRAS proto-oncogene GTPase)
    |
    Keytruda (pembrolizumab) • MK-1084
    8ms
    A Study of MK-1084 in KRAS Mutant Advanced Solid Tumors (MK-1084-001) (clinicaltrials.gov)
    P1, N=830, Recruiting, Merck Sharp & Dohme LLC | N=450 --> 830
    Enrollment change • Combination therapy • Metastases
    |
    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 • MK-1084
    9ms
    A Study of MK-1084 Plus Pembrolizumab (MK-3475) in Participants With KRAS G12C Mutant, Metastatic Non-small Cell Lung Cancer (NSCLC) With Programmed Cell Death Ligand 1 (PD-L1) Tumor Proportion Score (TPS) ≥50% (MK-1084-004) (clinicaltrials.gov)
    P3, N=600, Not yet recruiting, Merck Sharp & Dohme LLC
    New P3 trial
    |
    KRAS (KRAS proto-oncogene GTPase)
    |
    Keytruda (pembrolizumab) • MK-1084
    1year
    A phase 1, open-label, multicenter study evaluating MK-1084 as monotherapy and in combination with other therapies in patients with KRAS G12C mutant advanced solid tumors. (ASCO-GI 2024)
    ESMO 2023; Abs 3156) indicated antitumor activity in pts with solid tumors receiving oral MK-1084 monotherapy QD or BID (25 to 800 mg total daily; arm 1) and pts with previously untreated non–small-cell lung cancer (NSCLC) with PD-L1 tumor proportion score ≥1% receiving MK-1084 from 25 to 400 mg total daily dose plus pembrolizumab 200 mg IV Q3W (arm 2)...Pts in arms 5 and 6 receive MK-1084 with one of the following: cetuximab 500 mg/m2 IV Q2W (arm 5); or cetuximab 500 mg/m2 IV Q2W, oxaliplatin 85 mg/m2, leucovorin 400 mg/m2, and 5-fluorouracil per label IV Q2W (arm 6)...Study enrollment began in December 2021. Clinical trial information: NCT05067283.
    Clinical • P1 data • Combination therapy • PD(L)-1 Biomarker • IO biomarker • Metastases
    |
    PD-L1 (Programmed death ligand 1) • KRAS (KRAS proto-oncogene GTPase)
    |
    KRAS mutation • KRAS G12C • KRAS G12
    |
    Keytruda (pembrolizumab) • Erbitux (cetuximab) • 5-fluorouracil • oxaliplatin • leucovorin calcium • MK-1084
    over1year
    A Study of MK-1084 as Monotherapy and in Combination With Pembrolizumab (MK-3475) in Participants With KRAS G12C Mutant Advanced Solid Tumors (MK-1084-001) (clinicaltrials.gov)
    P1, N=450, Recruiting, Merck Sharp & Dohme LLC | N=264 --> 450 | Trial completion date: Feb 2026 --> Aug 2026 | Trial primary completion date: Feb 2026 --> Aug 2026
    Enrollment change • Trial completion date • Trial primary completion date • Combination therapy • Metastases
    |
    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 • MK-1084
    over2years
    A Study of MK-1084 as Monotherapy and in Combination With Pembrolizumab (MK-3475) in Participants With KRASG12C Mutant Advanced Solid Tumors (MK-1084-001) (clinicaltrials.gov)
    P1, N=264, Recruiting, Merck Sharp & Dohme LLC | N=185 --> 264
    Enrollment change • Combination therapy
    |
    KRAS (KRAS proto-oncogene GTPase)
    |
    KRAS mutation • KRAS G12C • KRAS G12
    |
    Keytruda (pembrolizumab) • MK-1084