A Phase 1/2 Open-Label, Multiple-Dose, Dose-Escalation Study to Investigate the Safety, Pharmacokinetics, and Pharmacodynamics of VMD-928 as Monotherapy and in Combination With Pembrolizumab in Subjects With Solid Tumors or Lymphoma
Summary
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
Detailed description
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.
Arms & interventions
- DrugVMD-928 100 mg Tablet
Taken orally once daily for 21 days per 21-day cycle
- DrugVMD-928 Tablet and Pembrolizumab (200 mg)
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.
Outcome measures
Primary
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
Secondary
Area under the plasma concentration versus time curve (AUC) of VMD-928.
Time frame: On Day 1 and Day 15 of Cycle 1 (each cycle is 21 days)
Peak plasma concentration (Cmax) of VMD-928.
Time frame: On Day 1 and Day 15 of Cycle 1 (each cycle is 21 days)
Incidence of Dose Limiting Toxicities.
Time frame: During the Cycle 1 (each cycle is 21 days)
Correlation between clinical antitumor and TrkA protein expression.
Time frame: Up to the end of the Cycle 2 (each cycle is 21 days)
Eligibility criteria
Study locations (14)
Providence Medical Foundation (site 209)
Santa Rosa, California, 95403
Hartford Hospital (site 210)
Hartford, Connecticut, 06102
The George Washington University Cancer Center (site 212)
Washington D.C., District of Columbia, 20037
Holy Cross Hospital (site 213)
Fort Lauderdale, Florida, 33308
Memorial Cancer Institute at Memorial Healthcare Systems (site 132)
Pembroke Pines, Florida, 33028
Englewood Hospital and Medical Center (site 202)
Englewood, New Jersey, 07631
Summit Medical Group (site 205)
Florham Park, New Jersey, 07932
Atlantic Health System, Morristown Medical Center (site 124)
Morristown, New Jersey, 07962
Presbyterian Kaseman Hospital (site 208)
Albuquerque, New Mexico, 87110
Weill Cornell Medicine, Cornell University (site 126)
New York, New York, 10065
Taylor Cancer Research Center (site 204)
Maumee, Ohio, 43537
Cancer Care Associates of York (site 206)
York, Pennsylvania, 17403
The University of Texas MD Anderson Cancer Center (site 127)
Houston, Texas, 77030
Utah Cancer Specialists (site 203)
Salt Lake City, Utah, 84106