An Open-Label, Multiple-Dose, Dose-Escalation Study to Investigate the Safety, Pharmacokinetics, and Pharmacodynamics of VMD-928 in Subjects With Solid Tumors or Lymphoma

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Started >3 years ago More information No known activity More information High burden on patient More information

Trial Details

Sponsor: VM Oncology, LLC (industry)

Phase: 1

Start date: June 8, 2018

Planned enrollment: 82

Trial ID: NCT03556228
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More trial details at ClinicalTrials.gov More info

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Goal: The trial aims to determine the safety, pharmacokinetics, pharmacodynamics, and preliminary antitumor activity of VMD-928, an oral selective TrkA inhibitor, in patients with advanced solid tumors or lymphoma that are refractory to standard therapies.

Patients: Adult patients with histologically or cytologically confirmed advanced solid tumors or lymphoma that are non-responsive to, or have progressed following, available therapies and for which no standard or curative therapy exists. Subjects are required to have good performance status (ECOG 0-1), adequate organ function, and tumors either overexpressing TrkA or harboring an NTRK1 gene fusion. Patients with active infections, significant comorbidities, or impaired drug absorption are excluded.

Design: This is a multicenter, open-label, first-in-human phase 1 study employing a multiple-dose, dose-escalation and expansion cohort design. Dose escalation uses an adaptive, accelerated titration scheme, followed by cohort expansion at the recommended phase 2 dose with collection of pre- and post-treatment tumor biopsies for correlative studies.

Treatments: The study investigates oral VMD-928, an investigational small molecule that irreversibly and allosterically inhibits TrkA by acting as a molecular glue to dimerize and inactivate the protein. VMD-928 is highly selective for TrkA, distinguishing it from current ATP-competitive pan-TRK inhibitors. Early phase results identified a recommended phase 2 dose of 600 mg twice daily, with dose-limiting toxicities including elevated liver enzymes and manageable adverse events such as dark stool and gastrointestinal symptoms. Preliminary evidence shows prolonged stable disease in at least one patient with adenoid cystic carcinoma. Expansion cohorts target tumors with high TrkA expression.

Outcomes: Primary outcome measures include the number and severity of treatment-emergent adverse events and dose-limiting toxicities. Secondary outcomes assess pharmacokinetics (AUC, Cmax), pharmacodynamics (change in TrkA expression), and exploratory correlations between TrkA expression, plasma exposure, analgesic response, and antitumor activity through two cycles of therapy.

Burden on patient: Patient burden is moderate to high. Phase 1 trials require frequent clinic visits for safety assessment, regular blood draws for pharmacokinetic sampling, and additional tumor biopsies both pre-treatment and after two cycles for pharmacodynamic studies. Analgesic response and clinical outcomes are closely monitored, and patients with advanced disease may experience increased travel and procedural burdens.

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Sites (15)

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PanOncology Trials, Hospital Oncologico - Puerto Rico Medical Center, Río Piedras (site 200)

San Juan, 00935, Puerto Rico

[email protected] / (787) 407-3333

Status: Recruiting

Providence Medical Foundation (site 209)

Santa Rosa, California, 95403, United States

[email protected] / 707-521-3833

Status: Recruiting

Hartford Hospital (site 210)

Hartford, Connecticut, 06102, United States

[email protected] / 860-972-5518

Status: Recruiting

The George Washington University Cancer Center (site 212)

Washington, District of Columbia, 20037, United States

[email protected] / 202-994-2524

Status: Recruiting

Memorial Cancer Institute at Memorial Healthcare Systems (site 132)

Pembroke Pines, Florida, 33028, United States

[email protected] / 954-844-9917

Status: Recruiting

Holy Cross Hospital (site 213)

Fort Lauderdale, Florida, 33308, United States

[email protected] / 954-542-7748

Status: Recruiting

Summit Medical Group (site 205)

Florham Park, New Jersey, 07932, United States

[email protected] / 973-436-1755

Status: Recruiting

Atlantic Health System, Morristown Medical Center (site 124)

Morristown, New Jersey, 07962, United States

[email protected] / 973-971-6373

Status: Recruiting

Englewood Hospital and Medical Center (site 202)

Englewood, New Jersey, 07631, United States

[email protected] / 201-608-2572

Status: Recruiting

Presbyterian Kaseman Hospital (site 208)

Albuquerque, New Mexico, 87110, United States

[email protected] / 505-559-6089

Status: Recruiting

Weill Cornell Medicine, Cornell University (site 126)

New York, New York, 10065, United States

[email protected] / 646-962-6091

Status: Recruiting

Taylor Cancer Research Center (site 204)

Maumee, Ohio, 43537, United States

[email protected] / 567.402.4502

Status: Recruiting

Cancer Care Associates of York (site 206)

York, Pennsylvania, 17403, United States

[email protected] / 1-717-741-9229

Status: Recruiting

The University of Texas MD Anderson Cancer Center (site 127)

Houston, Texas, 77030, United States

[email protected] / 713-563-2169

Status: Recruiting

Utah Cancer Specialists (site 203)

Salt Lake City, Utah, 84106, United States

[email protected] / 801-269-0231

Status: Recruiting