Phase Ib Trial of the KRAS G12C Inhibitor Adagrasib (MRTX849) in Combination With the PARP Inhibi… (NCT06130254) | Clinical Trial Compass
TerminatedPhase 1
Phase Ib Trial of the KRAS G12C Inhibitor Adagrasib (MRTX849) in Combination With the PARP Inhibitor Olaparib in Patients With KRAS G12C Mutated Advanced Solid Tumors, With a Focus on Gynecological, Breast, Pancreatic and KEAP1 Mutated Non-small Cell Lung Cancers
Stopped: Sponsor discontinued the trial
United States1 participantsStarted 2024-01-30
Plain-language summary
Evaluate safety and tolerability, while establishing the recommended dose of the investigational drug combination of adagrasib and olaparib that can be given to participants with advanced solid tumor(s) with a KRAS G12C and/or KEAP1 mutation.
Who can participate
Age range18 Years
SexALL
See this in plain English?
AI-rewrites the medical criteria so a patient or caregiver can understand them. Always confirm with the trial site.
Inclusion criteria
✓. Dose escalation cohort: Histologically confirmed diagnosis of a solid tumor malignancy with a KRAS G12C mutation. Participants are eligible based on detection of these mutations in tumor tissue or plasma circulating tumor DNA (ctDNA) with a minimum VAF of 1%.
✓. Dose expansion cohort 1: Histologically confirmed diagnosis advanced pancreatic cancer with KRAS G12C mutation. Participants must have progressed on at least 1 prior line of standard systemic therapy and must be eligible based on detection of KRAS G12C mutation in tumor tissue or ctDNA with a minimum VAF of 1%.
✓. Dose expansion cohort 2: Histologically confirmed diagnosis of advanced breast cancer with KRAS G12C mutation. Participants must have progressed on at least 1 prior line of standard systemic therapy and must be eligible based on detection of KRAS G12C mutation in tumor tissue or ctDNA with a minimum VAF of 1%.
✓. Dose expansion cohort 3: Histologically confirmed diagnosis of advanced uterine or epithelial ovarian cancer with KRAS G12C mutation. Participants must have progressed on at least 1 prior line of standard systemic therapy and must be eligible based on detection of KRAS G12C mutation in tumor tissue or ctDNA with a minimum VAF of 1%.
✓. Dose expansion cohort 4: Histologically confirmed diagnosis of NSCLC with KRAS G12C and KEAP1 co-mutations. Participants must have progressed on at least 1 prior line of standard systemic therapy and must be eligible based on detection of KRAS G12C and KEAP1 co-mutations in tumor tissue or plasma circulating tumor DNA (ctDNA) with a minimum VAF of 1%.
What they're measuring
1
Incidence of Adverse Events, Graded According to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version (v) 5.0
Timeframe: through study completion; an average of 1 year.
✓. Unresectable or metastatic disease and for which standard curative or palliative measures do not exist or are no longer effective.
✓. Participants must have evaluable or measurable disease per RECIST v1.1 for the dose escalation cohort and must have measurable disease per RECIST v1.1 for dose expansion cohorts 1-4.
✓. Participants with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial.
Exclusion criteria
✕4. Men treated or enrolled on this protocol must also agree to use adequate contraception and avoid donating sperm prior to the study, for the duration of study participation, and 6 months after completion of the trial.
✕5. Prior treatment with a therapy targeting PARP or KRAS G12C mutation is permitted.
✕6. Ability to understand and the willingness to sign a written informed consent document.
✕7. Willing to comply with clinical trial instructions and requirements.
✕. Active brain metastases. Patients are eligible if brain metastases are adequately treated and patients are neurologically stable (which is assessed in a case-by-case by the treating physician based on the likelihood of central nervous system (CNS) activity - except for residual signs or symptoms related to the CNS treatment- and by the lack of corticosteroid dosing or by having a stable or decreasing dose of ≤ 10 mg daily prednisone, or equivalent) for at least 2 weeks prior to enrollment.
✕. Participants with carcinomatous meningitis.
✕. Participants with myelodysplastic syndrome/acute myeloid leukemia or with features suggestive of MDS/AML.
✕. Participants who have not recovered from adverse events due to prior anti-cancer therapy (i.e., have residual toxicities \> Grade 1), excluding alopecia.