Cancerify Logo
Log inSign up
Back to clinical trials
RecruitingInterventionalPhase 1

A Phase 1, Open-label, Multicenter Study to Assess Safety, Tolerability, PK, and Efficacy of MK-1084 as Monotherapy and as Part of Various Combination Therapies in Participants With KRAS G12C Mutant Advanced Solid Tumors

NCT ID: NCT05067283Sponsor: Merck Sharp & Dohme LLCLast updated: 2026-05-26

Summary

This is a study evaluating the safety, pharmacokinetics, and efficacy of calderasib alone, and calderasib plus other combination therapies in participants with advanced solid tumors with identified kirsten rat sarcoma viral oncogene homolog G12C (KRAS G12C) mutation.

Arms & interventions

  • DrugCalderasib

    Oral dose

  • BiologicalPembrolizumab

    Intravenous infusion of 200 mg

  • Drugcarboplatin

    Per label

  • Drugpemetrexed

    Per label

  • Biologicalcetuximab

    Per label

  • Drugoxaliplatin

    Per label

  • Drugleucovorin

    Per label

  • Drug5-fluorouracil

    Per label

Outcome measures

Primary

  • Number of Participants Who Experience a Dose-Limiting Toxicity (DLT)

    A DLT is defined as an event with toxicity including the type, severity, time of onset, time of resolution, and the probable association with study treatment that are not due to pre-existing conditions as defined by the Common Terminology Criteria for Adverse Events Version 5.0 (CTCAE 5.0). Number of participants who experience a DLT will be reported.

    Time frame: Up to ~21 days

  • Number of Participants Who Experience an Adverse Event (AE)

    An AE is any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product or protocol-specified procedure, whether or not considered related to the medicinal product or protocol-specified procedure. Any worsening of a preexisting condition that is temporally associated with the use of the Sponsor's product, is also an AE. The number of participants who experience an AE will be reported.

    Time frame: Up to ~56 months

  • Number of Participants Who Discontinue Study Treatment Due to an AE

    An AE is any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product or protocol-specified procedure, whether or not considered related to the medicinal product or protocol-specified procedure. Any worsening of a preexisting condition that is temporally associated with the use of the Sponsor's product, is also an AE. The number of participants who discontinue study treatment due to an AE will be reported.

    Time frame: Up to ~56 months

Secondary

  • Objective Response Rate (ORR)

    Time frame: Up to ~56 months

  • Duration of Response (DOR)

    Time frame: Up to ~56 months

  • Mean Plasma Concentration of calderasib

    Time frame: At designated timepoints during the study in Cycles 1, 2, 3, 5, 9, 13, 17, 21, 25, and every 6 weeks thereafter up to 56 months. Cycle=3 weeks (Arms 1-4) and 4 weeks (Arms 5-6)

  • Maximum Concentration (Cmax) of calderasib

    Time frame: At designated timepoints during the study in Cycles 1, 2, 3, 5, 9, 13, 17, 21, 25, and every 6 weeks thereafter up to 56 months. Cycle=3 weeks (Arms 1-4) and 4 weeks (Arms 5-6).

  • Time to Maximum Concentration (Tmax) of calderasib

    Time frame: At designated timepoints during the study in Cycles 1, 2, 3, 5, 9, 13, 17, 21, 25, and every 6 weeks thereafter up to 56 months. Cycle=3 weeks (Arms 1-4) and 4 weeks (Arms 5-6)

  • Minimum Concentration (Cmin) of calderasib

    Time frame: At designated timepoints during the study in Cycles 1, 2, 3, 5, 9, 13, 17, 21, 25, and every 6 weeks thereafter up to 56 months. Cycle=3 weeks (Arms 1-4) and 4 weeks (Arms 5-6)

  • Area Under the Concentration Time-Curve 0-12 Hours (AUC 0-12) of calderasib

    Time frame: At designated timepoint during the study in Cycle 1 Day 1: Predose and up to 12 hours postdose. Cycle=3 weeks (Arms 1-4) and 4 weeks (Arms 5-6)

  • Area Under the Concentration Time-Curve 0-24 Hours (AUC 0-24) of calderasib

    Time frame: At designated timepoint during the study in Cycle 1 Day 1: Predose and up to 24 hours postdose. Cycle=3 weeks (Arms 1-4) and 4 weeks (Arms 5-6)

  • Half-Life (t1/2) of calderasib

    Time frame: At designated timepoint during the study in Cycle 1 Day 1: Predose and up to 24 hours postdose. Cycle=3 weeks (Arms 1-4) and 4 weeks (Arms 5-6)

Eligibility criteria

Sex: AllAge: 18 Years and olderHealthy volunteers: No
Inclusion Criteria: For all participants: * Has measurable disease by RECIST 1.1 criteria * Has adequate organ function * Male participants agree to protocol-specified contraception requirements including refraining from donating sperm and using protocol-specified contraceptives unless confirmed to be azoospermic * Female participants must not be pregnant or breastfeeding, and must agree to protocol-specified contraceptive requirements and must have a negative highly sensitive pregnancy test within 24 hours (for a urine test) or 72 hours (for a serum test) before the first dose of study intervention For Arm 1 - Has locally advanced unresectable or metastatic solid-tumor malignancy with histologically OR blood-based confirmation of KRAS G12C mutation who has received at least 1 line of therapy for systemic disease For Arm 2 \- Has an untreated metastatic non-small cell lung cancer (NSCLC) with histologically OR blood-based confirmation of KRAS G12C mutation and histologic confirmation of programmed cell death ligand 1 (PD-L1) tumor proportion score (TPS) ≥1% For Arm 3 * Has locally advanced unresectable or metastatic solid-tumor malignancy with histologically or blood-based confirmation of KRAS G12C mutation who has received at least 1 line of therapy for systemic disease Expansion Group A: 2L+NSCLC * Has histologically or cytologically confirmed diagnosis of unresectable or metastatic NSCLC with histological or blood-based confirmation of KRAS G12C mutation and submits archival tumor sample * Previous treatment failure of at least 1 line of systemic therapy Expansion Group B * Has locally advanced unresectable or metastatic solid-tumor malignancy, excluding NSCLC or CRC, with histologically or blood- based confirmation of KRAS G12C mutation who has received at least 1 line of therapy for systemic disease Arm 4 only - Has an untreated advanced or metastatic nonsquamous NSCLC with histologically or blood-based confirmation of KRAS G12C mutation Arm 5 only * Histologically or cytologically confirmed diagnosis of locally advanced unresectable or metastatic colorectal adenocarcinoma and with histologically or blood-based confirmation of KRAS G12C mutation * Previous treatment failure of one or 2 previous line(s) of systemic therapy Arm 6 only \- Locally advanced unresectable or metastatic colorectal adenocarcinoma with histologically or blood-based confirmation of KRAS G12C mutation Exclusion Criteria: * Has received chemotherapy, definitive radiation, or biological cancer therapy within 4 weeks (2 weeks for palliative radiation) before first dose of study intervention * Has a history of second malignancy, unless potentially curative treatment has been completed with no evidence of malignancy for 5 years * Has clinically active central nervous system (CNS) metastases and/or carcinomatous meningitis * Has an active infection requiring systemic therapy * Known history of HIV infection or. has a known history of Hepatitis B virus or known active Hepatitis C virus infection * Has a history of interstitial lung disease, noninfectious pneumonitis requiring active steroid therapy, or ongoing pneumonitis * Has an active autoimmune disease requiring systemic therapy * Has not fully recovered from any effects of major surgical procedure without significant detectable infection * Has one or more of the following ophthalmological findings/conditions: intraocular pressure \>21 mm Hg and/or any diagnosis of glaucoma; diagnosis of central serous retinopathy, retinal vein occlusion, or retinal artery occlusion and/or a diagnosis of retinal degenerative disease * Has received live or live-attenuated vaccine within 4 weeks of study start Arm 4 Only * Is unable to interrupt aspirin or other nonsteroidal anti-inflammatories (NSAIDs), other than an aspirin dose ≤1.3 grams per day, for at least 2 days (5 days for long-acting agents \[for example, piroxicam\]) before, during, and for at least 2 days after administration of pemetrexed. * Is unable/unwilling to take folic acid, vitamin B12, and dexamethasone

Study locations (6)

Moffitt Cancer Center ( Site 0261)

Tampa, Florida, 33612

Recruiting
Study Coordinator · Contact

START Midwest ( Site 0267)

Grand Rapids, Michigan, 49546

Recruiting
Study Coordinator · Contact

John Theurer Cancer Center at Hackensack University Medical Center ( Site 0260)

Hackensack, New Jersey, 07601

Recruiting
Study Coordinator · Contact

Laura and Isaac Perlmutter Cancer Center ( Site 0270)

New York, New York, 10016

Completed

NEXT Virginia ( Site 0271)

Fairfax, Virginia, 22031

Recruiting
Study Coordinator · Contact

MEDICAL COLLEGE OF WISCONSIN-Cancer Center Clinical Trials Office ( Site 0262)

Milwaukee, Wisconsin, 53226

Recruiting
Study Coordinator · Contact

References

  • Ma X, Sloman DL, Duggal R, Anderson KD, Ballard JE, Bharathan I, Brynczka C, Gathiaka S, Henderson TJ, Lyons TW, Miller R, Munsell EV, Orth P, Otte RD, Palani A, Rankic DA, Robinson MR, Sather AC, Solban N, Song XS, Wen X, Xu Z, Yang Y, Yang R, Day PJ, Stoeck A, Bennett DJ, Han Y. Discovery of MK-1084: An Orally Bioavailable and Low-Dose KRASG12C Inhibitor. J Med Chem. 2024 Jul 11;67(13):11024-11052. doi: 10.1021/acs.jmedchem.4c00572. Epub 2024 Jun 26.(PubMed)