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

What's the purpose of this trial?

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

This trial is currently open and accepting patients.


What will happen during the trial?

You may be able to join this trial if you:

The following criteria is a partial list of reasons why patients may be eligible to participate in this clinical trial. Further evaluation with a medical professional is required.

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.

Additional Trial Information

Phase 1/2

Enrollment: 242 patients (estimated)

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Trial Locations

All Trial Locations

View all clinical trial locations sorted by state.

California

Providence Medical Foundation - Santa Rosa

Santa Rosa, CA

Open and Accepting

Connecticut

Hartford Hospital

Hartford, CT

Open and Accepting

Florida

Holy Cross Hospital

Fort Lauderdale, FL

Open and Accepting

Memorial Cancer Institute Memorial Hospital West

Pembroke Pines, FL

Open and Accepting

New Jersey

Englewood Hospital and Medical Center

Englewood, NJ

Open and Accepting

Summit Health

Florham Park, NJ

Open and Accepting

Morristown Medical Center Atlantic Health System

Morristown, NJ

Open and Accepting

New Mexico

Presbyterian Kaseman Hospital - New Mexico Cancer Research Alliance (NMCRA)

Albuquerque, NM

Open and Accepting

New York

Weill Cornell

New York, NY

Open and Accepting

Ohio

Toledo Clinic Cancer Centers

Maumee, OH

Open and Accepting

Pennsylvania

Cancer Care Associates of York

York, PA

Open and Accepting

Texas

MD Anderson Cancer Center The University of Texas

Houston, TX

Open and Accepting

Utah

Utah Cancer Specialists Cancer Center

Salt Lake City, UT

Open and Accepting

Washington, D.C.

George Washington University Hospital

Washington, DC

Open and Accepting
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