A Study of Calderasib (MK-1084) in KRAS Mutant Advanced Solid Tumors (MK-1084-001)
ConditionAdvanced Solid Tumors
Trial statusRecruiting
Trial phasePhase 1
Trial typeInterventional
Biological sexAll
Age18+
SponsorMerck Sharp & Dohme LLC
About this trial
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.
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
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
Disqualifiers
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
Trial design
Design model
Parallel
Treatments tested in this trial
Calderasib
DrugOral dose
Pembrolizumab
Biological/VaccineIntravenous infusion of 200 mg
carboplatin
DrugPer label
pemetrexed
DrugPer label
cetuximab
Biological/VaccinePer label
oxaliplatin
DrugPer label
leucovorin
DrugPer label
5-fluorouracil
DrugPer label
Treatment groups
830 Participants
are divided into 6 treatment groups6
Treatment groupsSee each treatment group below.
Group A: Arm 1Experimental treatment 1 intervention
Group B: Arm 2Experimental treatment 2 interventions
Group C: Arm 3Experimental treatment 1 intervention
Group D: Arm 4Experimental treatment 4 interventions
Group E: Arm 5Experimental treatment 2 interventions
Group F: Arm 6Experimental treatment 5 interventions
Trial outcomes
Primary outcomes
1
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 days2
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 months3
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 monthsSecondary outcomes
1
Objective Response Rate (ORR)
ORR is defined as the percentage of participants who have a Complete Response (CR: Disappearance of all target lesions) or a Partial Response (PR: At least a 30% decrease in the sum of diameters of target lesions) per Response Evaluation Criteria in Solid Tumors 1.1 (RECIST 1.1). The percentage of participants who experience a CR or PR as assessed by the investigator based on RECIST 1.1 will be reported.
Time frame
Up to ~56 months2
Duration of Response (DOR)
DOR is defined as the time from first documented evidence of CR or PR until progressive disease (PD) or death. Per RECIST 1.1, PD is defined as at least a 20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. The appearance of one or more new lesions is also considered PD. The DOR as assessed by the investigator will be reported.
Time frame
Up to ~56 months3
Mean Plasma Concentration of calderasib
Mean Plasma Concentration of calderasib determined by blood samples collected pre-dose and at designated timepoints post-dose will be reported.
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)4
Maximum Concentration (Cmax) of calderasib
Cmax of calderasib determined by blood samples collected pre-dose and at designated timepoints post-dose will be reported.
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).Sponsors and contacts
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Source ClinicalTrials.gov