Selective TrkA Inhibitor VMD-928 to Treat TrkA Overexpression Driven Solid Tumors or Lymphoma

Phase 1

Recruiting

• Conditions: Head and Neck Carcinoma; Adenoid Cystic Carcinoma; Lung Cancer; Non-Small Cell Lung Cancer; Breast Cancer; Pancreatic Cancer; Mesothelioma; Thymic Carcinoma; Cervical Cancer; Ovarian Cancer
• Interventions: Drug: VMD-928 300 mg Tablet (ongoing); 100 mg Capsule (complete)

• Registration Number: NCT03556228
• Lead Sponsor: VM Oncology, LLC

Brief Summary

This is a multicenter, open-label, Phase 1 study of orally administered VMD-928 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, Phase I, FTIH, multiple-dose, dose-escalation and cohort expansion multi-center study conducted in three parts to identify a safe and pharmacologically active dose and regimen for VMD-928 monotherapy, which can be implemented in Phase 2 studies (the RP2D). The regimen will be identified using an adaptive design, multiple-ascending dose study in cancer patients. To conserve patients in the lower dose cohorts, dose escalation will begin with an accelerated titration scheme. A second part of the study will assess antitumor activity at the RP2D. The third part of the study will collect tumor samples before and after treatment to assess biological activity.

Study Timeline

• Study First Submitted: 2018-04-29
• Study First Submitted QC: 2018-06-01
• Study Start: 2018-06-08
• Study First Posted: 2018-06-14
• Status Verified: 2025-04
• Last Update Submitted: 2025-04-15
• Last Update Posted: 2025-04-17
• Primary Completion: 2026-07
• Study Completion: 2026-12

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 82

Inclusion Criteria

• Histologically or cytologically confirmed diagnosis of any type of solid tumor malignancy or lymphoma that is not responsive to standard therapies or had progressed following standard therapy 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.

• ECOG score of 0 or 1.

• Able to swallow and retain oral medication.

• Adequate organ system function.

• Subjects must either have available archival tumor tissue samples, or consent to tumor tissue sampling prior to the first dose, that is sufficient for IHC analysis of TrkA expression.

• Subjects must have a tumor:

  (i). with TrkA protein overexpression (TrkA+) in the validated TrkA IHC assay, OR (ii). with documented NTRK1 gene fusion (NTRK1+) including a tumor which has progressed due to NTRK1 mutation after treatment of a pan-Trk inhibitor (e.g. larotrectinib or entrectinib)

• 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

1. Received chemotherapy having delayed toxicity within the last 14 days (six weeks for prior nitrosourea or mitomycin C).
2. Received anticancer therapy with radiation, immunotherapy, and a biologic, surgery and/or tumor embolization within the past 2 weeks.
3. 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.
4. 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.
5. Negative result on TrkA immunohistochemistry (IHC) assay.
6. Known active infections including HIV disease.
7. Patients with a history of chronic viral hepatitis (HBV/HCV) or a history of cirrhotic liver secondary to any etiology (i.e. alcoholism, non-alcoholic steatohepatitis).
8. Currently pregnant, nursing, or planning to become pregnant during the course of the study.
9. QTcF interval ≥ 480 msec.
10. Class II, III, or IV heart failure as defined by the New York Heart Association (NYHA) functional classification system.
11. Acute coronary syndromes (including unstable angina), coronary angioplasty, or stenting within the past 24 weeks.
12. Unstable or uncompensated respiratory, hepatic, renal, or cardiac disease that would compromise the patient's safety or interfere with assessment of the drug.
13. 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.
14. Known immediate or delayed hypersensitivity reaction or idiosyncrasy to the study drug, or excipients

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SEQUENTIAL

Arm && Interventions

Group	Intervention	Description
VMD-928 300 mg Tablet (ongoing); 100 mg Capsule (complete)	VMD-928 300 mg Tablet (ongoing); 100 mg Capsule (complete)	-

Primary Outcome Measures

Name	Time	Method
Number and severity of treatment-emergent AEs	Within 2 cycles (each cycle is 28 days)

Secondary Outcome Measures

Name	Time	Method
Area under the plasma concentration versus time curve (AUC) of VMD-928.	On Day 1 and Day 15 of Cycle 1 (each cycle is 28 days)
Peak plasma concentration (Cmax) of VMD-928.	On Day 1 and Day 15 of Cycle 1 (each cycle is 28 days)
Incidence of Dose Limiting Toxicities.	During the Cycle 1 (each cycle is 28 days)
Analgesic response as defined by the Brief Pain Inventory (BPI).	On Day 1 and Day 15 of Cycle 1 (each cycle is 28 days)
Change in TrkA protein expression.	Pre-dose and at the end of Cycle 2 (each cycle is 28 days)
Correlation between clinical antitumor and AUC.	Up to the end of the Cycle 2 (each cycle is 28 days)
Correlation between clinical antitumor and TrkA protein expression.	Up to the end of the Cycle 2 (each cycle is 28 days)
Correlation between analgesic response and TrkA protein expression.	Up to the end of the Cycle 2 (each cycle is 28 days)
Correlation between analgesic response and AUC.	Up to the end of the Cycle 2 (each cycle is 28 days)

Trial Locations

Locations (14)

Providence Medical Foundation (site 209); 🇺🇸 Santa Rosa, California, United States

Hartford Hospital (site 210); 🇺🇸 Hartford, Connecticut, United States

The George Washington University Cancer Center (site 212); 🇺🇸 Washington, District of Columbia, United States

Memorial Cancer Institute at Memorial Healthcare Systems (site 132); 🇺🇸 Pembroke Pines, Florida, United States

Englewood Hospital and Medical Center (site 202); 🇺🇸 Englewood, New Jersey, United States

Summit Medical Group (site 205); 🇺🇸 Florham Park, New Jersey, United States

Atlantic Health System, Morristown Medical Center (site 124); 🇺🇸 Morristown, New Jersey, United States

Presbyterian Kaseman Hospital (site 208); 🇺🇸 Albuquerque, New Mexico, United States

Weill Cornell Medicine, Cornell University (site 126); 🇺🇸 New York, New York, United States

Taylor Cancer Research Center (site 204); 🇺🇸 Maumee, Ohio, United States

Cancer Care Associates of York (site 206); 🇺🇸 York, Pennsylvania, United States

The University of Texas MD Anderson Cancer Center (site 127); 🇺🇸 Houston, Texas, United States

Utah Cancer Specialists (site 203); 🇺🇸 Salt Lake City, Utah, United States

PanOncology Trials, Hospital Oncologico - Puerto Rico Medical Center, Río Piedras (site 200); 🇵🇷 San Juan, Puerto Rico