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

December 4, 2025 updated by: VM Oncology, LLC

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

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

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Estimated)

242

Phase

  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • Puerto Rico
      • San Juan, Puerto Rico, 00935
        • Recruiting
        • PanOncology Trials, Hospital Oncologico - Puerto Rico Medical Center, Río Piedras (site 200)
        • Principal Investigator:
          • Marcia Cruz-Correa, MD, PhD, AGAF, FASGE
        • Contact:
        • Contact:
  • United States
    • California
      • Santa Rosa, California, United States, 95403
    • Connecticut
      • Hartford, Connecticut, United States, 06102
    • District of Columbia
      • Washington D.C., District of Columbia, United States, 20037
        • Recruiting
        • The George Washington University Cancer Center (site 212)
        • Contact:
        • Contact:
        • Principal Investigator:
          • Sonal Paul, MD
    • Florida
      • Fort Lauderdale, Florida, United States, 33308
      • Pembroke Pines, Florida, United States, 33028
        • Recruiting
        • Memorial Cancer Institute at Memorial Healthcare Systems (site 132)
        • Contact:
        • Principal Investigator:
          • Luis E Raez, MD
        • Contact:
    • New Jersey
      • Englewood, New Jersey, United States, 07631
      • Florham Park, New Jersey, United States, 07932
      • Morristown, New Jersey, United States, 07962
    • New Mexico
      • Albuquerque, New Mexico, United States, 87110
        • Recruiting
        • Presbyterian Kaseman Hospital (site 208)
        • Contact:
        • Contact:
        • Principal Investigator:
          • Ethan Binder, MD
    • New York
      • New York, New York, United States, 10065
        • Recruiting
        • Weill Cornell Medicine, Cornell University (site 126)
        • Contact:
        • Principal Investigator:
          • Barbara Ma, M.D., M.S.
        • Contact:
    • Ohio
      • Maumee, Ohio, United States, 43537
        • Recruiting
        • Taylor Cancer Research Center (site 204)
        • Contact:
        • Contact:
        • Principal Investigator:
          • John J Nemunaitis, MD
    • Pennsylvania
      • York, Pennsylvania, United States, 17403
    • Texas
      • Houston, Texas, United States, 77030
        • Recruiting
        • The University of Texas MD Anderson Cancer Center (site 127)
        • Principal Investigator:
          • David S Hong, MD
        • Contact:
        • Contact:
    • Utah

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

14 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

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 Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Sequential Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: VMD-928 monotherapy
VMD-928 tablet monotherapy
Drug: VMD-928 100 mg Tablet
Taken orally once daily for 21 days per 21-day cycle
Other Names:
  • Monotherapy
Experimental: Combination Therapy
VMD-928 tablet in combination with fixed dose of pembrolizumab 200 mg once-very-21-day (per cycle)
Drug: VMD-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.
Other Names:
  • Combination therapy

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Number and severity of treatment-emergent Adverse Events (Phase 1)
Time Frame: First cycle (21 days per cycle)
TEAE
First cycle (21 days per cycle)
To determine the recommended Phase 2 dose for VMD-928 (Phase 1)
Time Frame: First cycle (21 days per cycle)
RP2D of monotherapy
First cycle (21 days per cycle)
To determine the RP2D of VMD-928 in combination with pembrolizumab (Phase 1)
Time Frame: First cycle (21 days per cycle)
RP2D of combination therapy
First cycle (21 days per cycle)
Antitumor activity of VMD-928 in subjects with TrkA-driven tumors (Phase 2)
Time Frame: Up to 18 months
Antitumor efficacy signal for monotherapy
Up to 18 months
Antitumor activity of VMD-928 in combination with pembrolizumab in subjects with TrkA-driven tumors (Phase 2)
Time Frame: Up to 18 months
Antitumor efficacy signal for combination therapy
Up to 18 months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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)
AUC
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)
Cmax
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)
# of DLTs
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)
Relationship of TrkA vs. efficacy
Up to the end of the Cycle 2 (each cycle is 21 days)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

VM Oncology, LLC

Investigators

  • Study Chair: Clinical Development, VM Oncology

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

June 8, 2018

Primary Completion (Estimated)

December 1, 2027

Study Completion (Estimated)

June 1, 2028

Study Registration Dates

First Submitted

April 29, 2018

First Submitted That Met QC Criteria

June 1, 2018

First Posted (Actual)

June 14, 2018

Study Record Updates

Last Update Posted (Actual)

December 11, 2025

Last Update Submitted That Met QC Criteria

December 4, 2025

Last Verified

December 1, 2025

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • VMO-01C

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

UNDECIDED

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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