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Treatment of solid tumors or lymphoma with VMD-928

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

Phase1; Phase2 Interventional VM Oncology, LLC · NCT03556228

This study is testing a new oral medication called VMD-928 to see if it can help adults with advanced solid tumors or lymphoma that haven't improved with standard treatments.

Quick facts

PhasePhase1; Phase2
Study typeInterventional
Enrollment242 (estimated)
Ages18 Years to 80 Years
SexAll
SponsorVM Oncology, LLC Industry-sponsored
Drugs / interventionsPembrolizumab, chemotherapy, immunotherapy, radiation
Locations15 sites (Santa Rosa, California and 14 other locations)
Trial IDNCT03556228 on ClinicalTrials.gov

What this trial studies

This multicenter, open-label Phase 1 study evaluates the safety and pharmacological activity of VMD-928, an orally administered selective TrkA inhibitor, in adult patients with advanced solid tumors or lymphoma that have not responded to standard therapies. The study is designed in three parts: an adaptive dose-escalation to determine the recommended Phase 2 dose (RP2D), an assessment of antitumor activity at the RP2D, and collection of tumor samples to evaluate biological activity. Patients will receive multiple doses of VMD-928, starting with an accelerated titration scheme to optimize dosing while conserving lower dose cohorts.

Who should consider this trial

Good fit: Ideal candidates include adults with advanced solid tumors or lymphoma that overexpress TrkA or have NTRK1 gene fusion and have exhausted other treatment options.

Not a fit: Patients with tumors that do not overexpress TrkA or have not been previously treated with standard therapies may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could provide a new therapeutic option for patients with advanced cancers that currently have no effective standard treatments.

How similar studies have performed: Other studies targeting TrkA overexpression have shown promise, indicating potential for success with this approach.

Eligibility criteria

Show full inclusion / exclusion 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.

Where this trial is running

Santa Rosa, California and 14 other locations

Study contacts

How to participate

  1. Review the eligibility criteria above with your treating physician.
  2. Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
  3. Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.
View on ClinicalTrials.gov → Find more trials like this →
Conditions Head and Neck CarcinomaAdenoid Cystic CarcinomaLung CancerNon-Small Cell Lung CancerPancreatic CancerMesotheliomaEsophageal CancerAny Solid Tumors Progressed After a Prior Immunotherapy
Last reviewed 2026-06-13 by the Find a Trial editorial team. Information on this page is for educational purposes and is not medical advice. Always consult qualified healthcare professionals about clinical trial participation.