This is a multicenter, open-label, Phase 1/2 study of orally administered VMD-928 monotherapy and in combination with pembrolizumab in adult subjects with advanced solid tumors or lymphoma that have progressed or are non responsive to available therapies and for which no standard or available curative therapy exists
This is an open-label, dose-escalation (Phase 1) and expansion (Phase 2) multi-center study conducted in five parts to identify the safe and pharmacologically active doses (MTD and/orRP2D) and regimen for oral VMD-928 monotherapy and in combination with a PD-1 inhibitor, pembrolizumab in cancer patients. An immunohistochemistry (IHC) assay specific for detecting TrkA protein in tumor tissue samples has been validated and is being used to detect TrkA protein expressions in patient tumor tissue samples at Pre-screening. The study is currently focusing on the top 5 solid tumor with the highest TrkA protein overexpression are: Head and Neck Cancers (HNC), Esophageal cancer, Lung cancers, Mesothelioma, and Pancreatic Cancer.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
242
Taken orally once daily for 21 days per 21-day cycle
VMD-928 tablet (oral) starting at 300 mg daily for 21 days of 21-day cycle. Pemprolizumab at fixed intravenous dose of 200 mg once-every-21 days (per cycle) for max. 6 cycles.
Providence Medical Foundation (site 209)
Santa Rosa, California, United States
RECRUITINGHartford Hospital (site 210)
Hartford, Connecticut, United States
RECRUITINGThe George Washington University Cancer Center (site 212)
Washington D.C., District of Columbia, United States
RECRUITINGHoly Cross Hospital (site 213)
Fort Lauderdale, Florida, United States
RECRUITINGMemorial Cancer Institute at Memorial Healthcare Systems (site 132)
Pembroke Pines, Florida, United States
RECRUITINGEnglewood Hospital and Medical Center (site 202)
Englewood, New Jersey, United States
RECRUITINGSummit Medical Group (site 205)
Florham Park, New Jersey, United States
RECRUITINGAtlantic Health System, Morristown Medical Center (site 124)
Morristown, New Jersey, United States
RECRUITINGPresbyterian Kaseman Hospital (site 208)
Albuquerque, New Mexico, United States
RECRUITINGWeill Cornell Medicine, Cornell University (site 126)
New York, New York, United States
RECRUITING...and 5 more locations
Number and severity of treatment-emergent Adverse Events (Phase 1)
TEAE
Time frame: First cycle (21 days per cycle)
To determine the recommended Phase 2 dose for VMD-928 (Phase 1)
RP2D of monotherapy
Time frame: First cycle (21 days per cycle)
To determine the RP2D of VMD-928 in combination with pembrolizumab (Phase 1)
RP2D of combination therapy
Time frame: First cycle (21 days per cycle)
Antitumor activity of VMD-928 in subjects with TrkA-driven tumors (Phase 2)
Antitumor efficacy signal for monotherapy
Time frame: Up to 18 months
Antitumor activity of VMD-928 in combination with pembrolizumab in subjects with TrkA-driven tumors (Phase 2)
Antitumor efficacy signal for combination therapy
Time frame: Up to 18 months
Area under the plasma concentration versus time curve (AUC) of VMD-928.
AUC
Time frame: On Day 1 and Day 15 of Cycle 1 (each cycle is 21 days)
Peak plasma concentration (Cmax) of VMD-928.
Cmax
Time frame: On Day 1 and Day 15 of Cycle 1 (each cycle is 21 days)
Incidence of Dose Limiting Toxicities.
\# of DLTs
Time frame: During the Cycle 1 (each cycle is 21 days)
Correlation between clinical antitumor and TrkA protein expression.
Relationship of TrkA vs. efficacy
Time frame: Up to the end of the Cycle 2 (each cycle is 21 days)
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