Phase 1/1b Study of MGCD516 in Patients With Advanced Cancer

Study Overview
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Brief Summary
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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
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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.

Official Title
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A Phase 1/1b Study of MGCD516 in Patients With Advanced Solid Tumor Malignancies

Conditions
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Advanced Cancer

Intervention / Treatment
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* Drug: MGCD516


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: MGCD516<br>MGCD516 oral capsule, administered in escalating doses in Phase 1, beginning with daily dosing and exploring other regimens as necessary, in 21 or 28 days cycles | Drug: MGCD516<br>* MGCD516 is a small molecule inhibitor of several closely related receptor tyrosine kinases. MGCD516 capsules will be taken with water.<br>* Other names: Sitravatinib;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | 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 Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Kind of metabolites of MGCD516 in blood plasma |  | Up to 9 weeks on treatment | 
| Concentration of selected marker proteins in blood plasma | Proteins include VEGF A, soluble VEGF-R2 and soluble MET | Up to 9 weeks on treatment | 
| Percent of patients having objective disease response to treatment | Response Evaluation Criteria in Solid Tumors (RECIST 1.1) | Up to 1 year on treatment | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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RET, MGCD516, MET, AXL, 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