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
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
Study locations (6)
Moffitt Cancer Center ( Site 0261)
Tampa, Florida, 33612
START Midwest ( Site 0267)
Grand Rapids, Michigan, 49546
John Theurer Cancer Center at Hackensack University Medical Center ( Site 0260)
Hackensack, New Jersey, 07601
Laura and Isaac Perlmutter Cancer Center ( Site 0270)
New York, New York, 10016
NEXT Virginia ( Site 0271)
Fairfax, Virginia, 22031
MEDICAL COLLEGE OF WISCONSIN-Cancer Center Clinical Trials Office ( Site 0262)
Milwaukee, Wisconsin, 53226
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)