Advanced Cancer
Conditions
Keywords
MGCD516, MET, AXL, RET, TRK, NTRK, DDR2, KDR, VEGFR, PDGFRA, KIT, Tyrosine kinase inhibitor, NSCLC, Non-small cell lung cancer, Head and neck cancer, Renal cell carcinoma, Prostate cancer, Phase 1, CBL, Sitravatinib
Brief summary
MGCD516 is a receptor tyrosine kinase (RTK) inhibitor shown in preclinical models to inhibit a closely related spectrum of RTKs including MET, AXL, MER, and members of the VEGFR, PDGFR, DDR2, TRK and Eph families. In this study, MGCD516 is orally administered to patients with advanced solid tumor malignancies to evaluate its safety, pharmacokinetic, metabolism, pharmacodynamic and clinical activity profiles. During the Phase 1 segment, the dose and regimen of MGCD516 will be assessed; during the Phase 1b segment, the clinical activity of MGCD516 will be evaluated in selected patient populations. Patients anticipated to be enrolled in Phase 1b will be selected based upon having a tumor type, including but not limited to, non small cell lung cancer and head and neck cancer positive for specific activating MET, NTRK2, NTRK3, or DDR2 mutations, MET or KIT/PDGFRA/KDR gene amplification, selected gene rearrangements involving the MET, RET, AXL, NTRK1, or NTRK3 gene loci, or having loss of function mutations in the CBL gene. In addition patients with clear cell renal cell carcinoma refractory to angiogenesis inhibitors or metastatic prostate cancer with bone metastasis will be enrolled.
Detailed description
During the Phase 1 segment, the dose and regimen of MGCD516 will be assessed. During the Phase 1b segment, the clinical activity of MGCD516 will be evaluated in selected patient populations. Patients anticipated to be enrolled in Phase 1b will be selected based upon the following cancer diagnosis: Non-small cell lung cancer with genetic alterations in MET, AXL, RET, TRK, DDR2, KDR, PDGFRA, KIT or CBL. Head and neck squamous cell carcinoma with genetic alterations in MET. Clear cell renal cell carcinoma refractory to angiogenesis inhibitors. Metastatic prostate cancer with bone metastases. Other cancer diagnosis having a selected genetic alteration in MGCD516 target RTKs.
Interventions
DRUGMGCD516
MGCD516 is a small molecule inhibitor of several closely related receptor tyrosine kinases. MGCD516 capsules will be taken with water.
Sponsors
Mirati Therapeutics Inc.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Metastatic or unresectable solid tumor malignancy * Standard treatment is not available * Adequate bone marrow and organ function
Exclusion criteria
* History of a significant cardiovascular illness * Prolonged corrected QT (QTc) interval * Left ventricular ejection fraction \< 40% * Symptomatic or uncontrolled brain metastases * Other active cancer
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Type of dose limiting adverse event | Up to 3 weeks on treatment |
| Area under the plasma concentration versus time curve (AUC) of MGCD516 | Up to 72 hours |
| Peak Plasma Concentration (Cmax) of MGCD516 | Up to 72 hours |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Kind of metabolites of MGCD516 in blood plasma | Up to 9 weeks on treatment | — |
| Concentration of selected marker proteins in blood plasma | Up to 9 weeks on treatment | Proteins include VEGF A, soluble VEGF-R2 and soluble MET |
| Percent of patients having objective disease response to treatment | Up to 1 year on treatment | Response Evaluation Criteria in Solid Tumors (RECIST 1.1) |
Countries
South Korea, United States
Outcome results
None listed