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VMD-928 Monotherapy and in Combination With Pembrolizumab to Treat TrkA Overexpression Driven Solid Tumors or Lymphoma

NCT03556228 · VM Oncology, LLC
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Official title
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
About this study
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.
Eligibility criteria
Key Inclusion Criteria: #. Histologically or cytologically confirmed diagnosis of any type of solid tumor malignancy or lymphoma: Phase 1 Dose Escalation only: Subjects with (A) any advanced solid tumors of 1. Head and Neck Cancers ("HNC") (of any types), 2. Esophageal cancer, 3. Lung cancers (of any types), 4. Mesothelioma, 5. Pancreatic cancers, Or, (B) any NTRK1 gene fusion positive ("NTRK1+") solid tumors or lymphomas, that is relapsed, refractory or intolerant (R/R/I) to standard of care (SOC) and for which there is no approved or curative therapy. Additionally, patients must not be candidates for or have exhausted regimens known to provide clinical benefit, including hematopoietic stem cell transplantation in lymphoma patients if they are deemed transplant eligible. Phase 2 Monotherapy and Combination with Pembrolizumab only: Subjects must have 1. TrkA-driven HNC, Esophageal, Lung, Mesothelioma, Pancreatic cancers; or, 2. any NTRK1+ solid tumors or lymphoma\*, that is R/R/I to SOC. Key Inclusion Criteria: * Eastern Cooperative Oncology Group (ECOG) Performance Status: 0 or 1. * Able to swallow and retain oral medication. * Subjects must either have available archival tumor tissue samples, or consent to tumor tissue sampling prior to the first dose. * Adequate organ system function as defined as follows: 1. Absolute neutrophil count ≥1.5x10\^9/L 2. Hemoglobin ≥9g/dL 3. Platelets ≥100x10\^9/L 4. PT/INR, PTT ≤1.5xULN 5. Total bilirubin ≤1.5x ULN 6. AST, ALT ≤2.5xULN 7. Creatinine ≤1.2xULN for age, weight 8. Calculated creatinine clearance or 24h urine creatinine clearance ≥60mL/min Key Exclusion Criteria: * Received chemotherapy having delayed toxicity within the last 14 days (six weeks for prior nitrosourea or mitomycin C). * Received anticancer therapy with radiation, immunotherapy, and a biologic, surgery and/or tumor embolization within the past 2 weeks. * Received an investigational anticancer drug within 14 days or 5 half-lives of the investigational agent, whichever is longer, prior to the first dose of VMD-928. Any exceptions to the above must be approved by the Sponsor Medical Monitor. * Unresolved toxicity from previous anticancer therapy \> CTCAE Grade 1 (except alopecia or anemia) unless agreed to by both the Sponsor Medical Monitor and the Investigator. * Known active infections including HIV disease. * Currently pregnant, nursing, or planning to become pregnant during the course of the study. * QTcF interval ≥ 480 msec. * Class II, III, or IV heart failure as defined by the New York Heart Association (NYHA) functional classification system. * Acute coronary syndromes (including unstable angina), coronary angioplasty, or stenting within the past 24 weeks. * Unstable or uncompensated respiratory, hepatic, renal, or cardiac disease that would compromise the patient's safety or interfere with assessment of the drug. * Psychological, familial, sociological, geographical, or other concurrent conditions that would interfere with safety evaluation, limit the patient's ability to follow the procedures in the protocol or otherwise jeopardize compliance with the protocol. Patients with uncontrolled major depression, bipolar disorder, or severe anxiety disorder are excluded. * Patient has had or is currently having other malignant tumors within 3 years. * Patients have multiple factors that affect their oral medication. * Patients have long-term unhealed wounds or fractures. * Patients have uncontrolled pleural effusion, pericardial effusion, or ascites that still require repeated drainage. * Patients are taking the following drugs and can't stop them during the study: * Tylenol or medicine containing acetaminophen (paracetamol). * Antacids (e.g. TUMS, calcium carbonate, or magnesium hydroxide), proton pump inhibitors (e.g. omeprazole), H2 blockers (e.g. famotidine), or buffered vitamins. * Epstein-Barr virus (EBV) negative nasopharyngeal carcinoma. For Phase 2 only: * Negative result on TrkA immunohistochemistry (IHC) assay. * Have visceral crisis, defined as severe organ dysfunction and rapid progression of the cancer. (It is not about presence of visceral metastasis.) For combination therapy with Pembrolizumab only: * Serious adverse immune related adverse events (grade 3 or 4) with previous PD-1(L1) inhibitor therapy, that were symptomatic and required prolong immunosuppression (\>6 weeks). * Any grade Pneumonitis and Myocarditis related to prior PD-1(L1) inhibitor therapy. * For subjects that received PD-1(L1) inhibitors before, there should be a washout period of at least 21 days between the last day of PD-1(L1) inhibitor and first day of study medications. * Subjects who relapsed after prior treatment with PD-1(L1) inhibitors. Relapsed is defined as patients having best overall response of CR or PR after treatment with a PD-1(L1) inhibitor.
Study design
Enrollment target: 242 participants
Allocation: non_randomized
Masking: none
Age groups: adult, older_adult
Timeline
Starts: 2018-06-08
Estimated completion: 2028-06
Last updated: 2025-12-11
Interventions
Drug: VMD-928 100 mg TabletDrug: VMD-928 Tablet and Pembrolizumab (200 mg)
Primary outcomes
  • Number and severity of treatment-emergent Adverse Events (Phase 1) (First cycle (21 days per cycle))
  • To determine the recommended Phase 2 dose for VMD-928 (Phase 1) (First cycle (21 days per cycle))
  • To determine the RP2D of VMD-928 in combination with pembrolizumab (Phase 1) (First cycle (21 days per cycle))
Sponsor
VM Oncology, LLC · industry
Contacts & investigators
ContactJay Wu, PhD · contact · OM@VMOncology.com · 1-510-270-2790
InvestigatorClinical Development · study_chair, VM Oncology
All locations (15)
Providence Medical Foundation (site 209)Recruiting
Santa Rosa, California, United States
Hartford Hospital (site 210)Recruiting
Hartford, Connecticut, United States
The George Washington University Cancer Center (site 212)Recruiting
Washington D.C., District of Columbia, United States
Holy Cross Hospital (site 213)Recruiting
Fort Lauderdale, Florida, United States
Memorial Cancer Institute at Memorial Healthcare Systems (site 132)Recruiting
Pembroke Pines, Florida, United States
Englewood Hospital and Medical Center (site 202)Recruiting
Englewood, New Jersey, United States
Summit Medical Group (site 205)Recruiting
Florham Park, New Jersey, United States
Atlantic Health System, Morristown Medical Center (site 124)Recruiting
Morristown, New Jersey, United States
Presbyterian Kaseman Hospital (site 208)Recruiting
Albuquerque, New Mexico, United States
Weill Cornell Medicine, Cornell University (site 126)Recruiting
New York, New York, United States
Taylor Cancer Research Center (site 204)Recruiting
Maumee, Ohio, United States
Cancer Care Associates of York (site 206)Recruiting
York, Pennsylvania, United States
The University of Texas MD Anderson Cancer Center (site 127)Recruiting
Houston, Texas, United States
Utah Cancer Specialists (site 203)Recruiting
Salt Lake City, Utah, United States
PanOncology Trials, Hospital Oncologico - Puerto Rico Medical Center, Río Piedras (site 200)Recruiting
San Juan, Puerto Rico
VMD-928 Monotherapy and in Combination With Pembrolizumab to Treat TrkA Overexpression Driven Solid Tumors or Lymphoma · TrialPath