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About
This research study is examining merestinib (a targeted therapy) as a possible treatment for non-small cell lung cancer (NSCLC) that was found to have a specific change in the MET gene (a MET exon 14 mutation); or as a treatment for solid tumors that have an alteration in the NTRK gene (an NTRK1, 2, or 3 rearrangement).
Full description
This is an open-label, phase II study of merestinib in patients with advanced NSCLC with a MET exon 14 mutation or patients with advanced cancer harboring an NTRK1, 2, or 3 rearrangement. Twenty patients with a MET mutation will be evaluated in a single-arm design. A small separate cohort of 5 NTRK patients will be evaluated for exploratory purposes.
Merestinib (LY2801653) is a small molecule that has been shown in vitro to be a reversible type II ATP-competitive inhibitor of MET. Pre-clinical testing also has shown merestinib to inhibit several other receptor tyrosine oncokinases including MST1R, FLT3, AXL, MERTK, TEK, ROS1, NTRK1/2/3, and DDR1/2 and the serine/threonine kinases MKNK1/2.
Enrollment
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Inclusion criteria
Baseline evaluations are to be conducted within 14 days prior to start of protocol therapy, with the exception of the informed consent and baseline tumor imaging which may be obtained up to 28 days prior to the start of protocol therapy.
For enrollment into the MET cohort: Participants must have a histologically or cytologically confirmed advanced NSCLC and must have received at least one prior line of therapy in the metastatic setting.
For enrollment into the NTRK cohort: Participants must have a histologically or cytologically confirmed advanced solid tumor and must have received at least one prior line of therapy in the metastatic setting.
Participants enrolling into the MET cohort must have a MET exon 14 mutation as confirmed by targeted NextGen Sequencing using the DFCI/BWH OncoPanel or another CLIA-certified method. Participants whose NSCLC specimens contain actionable genetic mutations/alterations (e.g. ALK/EGFR) should receive appropriate targeted therapies prior to enrollment in the trial.
Participants enrolling into the NTRK cohort must have an NTRK1, 2, or 3 rearrangement as confirmed by targeted NextGen Sequencing using the DFCI/BWH OncoPanel or another CLIA-certified method.
Participants must have measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded for non-nodal lesions and short axis for nodal lesions) as ≥ 20 mm with conventional techniques or as ≥ 10 mm with spiral CT scan, MRI, or calipers by clinical exam.
Participants enrolling to the MET cohort who have received treatment with a prior MET inhibitor must be able and willing to undergo a baseline tumor biopsy.
Participants enrolling to the NTRK cohort who have received treatment with a prior NTRK inhibitor must be able and willing to undergo a baseline tumor biopsy.
Age ≥ 18 years. As no dosing or adverse event data are currently available in participants < 18 years of age, children are excluded from this study but will be eligible for future pediatric trials.
ECOG performance status ≤ 1 (see Appendix A).
Participants must have normal organ and marrow function as defined below:
The effects of merestinib on the developing human fetus are unknown. For this reason and because MET inhibitor agents are known to be teratogenic, women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately. Men treated or enrolled on this protocol must also agree to use adequate contraception prior to the study, for the duration of study participation, and 4 months after completion of merestinib administration.
Ability to understand and the willingness to sign a written informed consent document.
Participants must be able to swallow and retain oral medication or have an enteral feeding tube in place for study drug administration.
Participants who have received prior oral tyrosine kinase inhibitors (TKIs) will be allowed on study if at least 5 half-lives have elapsed since the date of their last dose of TKI.
Exclusion criteria
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12 participants in 2 patient groups
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Data sourced from clinicaltrials.gov
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