RecruitingPhase 1 / Phase 2

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

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

Who can join

As published by the study on ClinicalTrials.gov. "Not stated" means the study hasn't said — ask the study team.

Age
18 Years to 80 Years
Sex
All sexes
Healthy volunteers
Not accepted
Compensation
Mentioned in the study description

Other requirements are listed under Eligibility below. Only the study team can confirm whether you can join.

What to expect

No one can promise a trial will help you personally — that is what the research is trying to find out.

What participation involves

Not stated in the study description — ask the study team about visits and procedures.

Compensation
Mentioned in the study description
  • Study-related exams and procedures are typically provided at no cost. This is how many trials work in general — confirm the details for this study with the study team.
  • Participants are monitored closely by the research team throughout the study.
  • Some participants may receive access to an investigational treatment, which is still being studied.
  • Your participation helps researchers learn whether this approach could help future patients.

About this study

In plain language

This study tests VMD-928, a medicine taken by mouth, alone or with pembrolizumab. It is for adults with certain advanced solid tumors or lymphoma, a cancer of the immune system. Their cancer must have worsened or not responded to available treatments, with no standard treatment or available cure.

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

Compensation is read from the study's own description and may be missing — always confirm with the study team.

Eligibility

Who can join

  • Have a solid tumor or lymphoma confirmed by a tissue or cell test.
  • For Phase 1: Have advanced head and neck, esophageal (food pipe), lung, pancreatic cancer, or mesothelioma (cancer of an organ's lining); or have a solid tumor or lymphoma with an NTRK1 gene fusion, a change that joins genes.
  • For Phase 2: Have one of the listed cancers driven by the TrkA protein, or a solid tumor or lymphoma with an NTRK1 gene fusion.
  • Cancer must have returned, resisted standard treatment, or treatment could not be tolerated. For Phase 1, treatments known to help must be used up or not suitable, including a stem cell transplant for eligible people with lymphoma.
  • Be fully active or able to do light work despite some limits on hard physical activity.
  • Be able to swallow medicine and keep it down.
  • Have a stored tumor sample available or agree to have a sample taken before treatment.
  • Meet the study's blood count, blood clotting, liver, and kidney test limits.

Who can't join

  • Recent cancer treatment: certain chemotherapy within 14 days (6 weeks for nitrosourea or mitomycin C); radiation, immune or biologic treatment, surgery, or tumor blood-vessel blocking within 2 weeks; or an experimental cancer drug within 14 days or longer, depending on how long it stays in the body. Some exceptions may be approved.
  • More than mild lasting side effects from past cancer treatment, except hair loss or anemia (low red blood cells), unless approved; an active infection, including HIV disease; or pregnancy, breastfeeding, or plans to become pregnant during the study.
  • Certain heart rhythm problems or heart failure; a recent serious heart blood-flow problem, heart artery procedure, or stent within 24 weeks; or unstable lung, liver, kidney, or heart disease.
  • Conditions that could make study visits, instructions, or safety checks difficult, including uncontrolled major depression, bipolar disorder, or severe anxiety; or another cancer within the past 3 years.
  • Problems affecting medicines taken by mouth; wounds or broken bones that have not healed for a long time; fluid around the lungs, heart, or belly needing repeated drainage; or inability to stop acetaminophen, acid-reducing medicines, antacids, or buffered vitamins.
  • Cancer behind the nose called nasopharyngeal carcinoma that tests negative for Epstein-Barr virus.
  • For Phase 2: A negative tumor test for TrkA, or rapidly worsening cancer causing severe organ problems.
  • For pembrolizumab combination treatment: Certain severe immune side effects from past PD-1/PD-L1 immune treatment needing over 6 weeks of immune-suppressing medicine; related lung or heart muscle inflammation; less than 21 days since that treatment; or cancer that returned after partly or fully shrinking with it.

Simplified for readability. The official criteria below are what the study team uses.

Official eligibility 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.

Study sites (14)

CA

CT

DC

FL

NJ

NM

NY

OH

PA

TX

UT