Selective TrkA Inhibitor VMD-928 to Treat TrkA Overexpression Driven Solid Tumors or Lymphoma

Launched by VM ONCOLOGY, LLC · Jun 1, 2018

Keywords

ClinConnect Summary

This clinical trial is studying a new medication called VMD-928, which is being tested for patients with certain types of advanced cancers and lymphomas that have not responded to standard treatments. These cancers include various types such as lung cancer, breast cancer, and pancreatic cancer, among others. The goal is to see if VMD-928 can help patients whose tumors overexpress a protein called TrkA, which may be driving their cancer. This trial is currently looking for adult participants who are not responding to available therapies and meet specific health criteria.

To be eligible for the trial, participants should have a confirmed diagnosis of a solid tumor or lymphoma that has progressed after previous treatments. They must also be in reasonably good health, capable of taking oral medications, and have available tumor samples for testing. Participants can expect to take the medication by mouth and will be monitored closely by the study team for any effects. It’s important to note that this trial is for patients who have limited treatment options, and individuals with certain health conditions or recent treatments may not be able to participate.

Gender

ALL

Eligibility criteria

• Key Inclusion Criteria:
• • Histologically or cytologically confirmed diagnosis of any type of solid tumor malignancy or lymphoma that is not responsive to standard therapies or had progressed following standard therapy 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.
• • ECOG score of 0 or 1.
• • Able to swallow and retain oral medication.
• • Adequate organ system function.
• • Subjects must either have available archival tumor tissue samples, or consent to tumor tissue sampling prior to the first dose, that is sufficient for IHC analysis of TrkA expression, except with prior documented NTRK+.
• * Subjects must have a tumor:
• • (i). with TrkA protein overexpression (TrkA+) in the validated TrkA IHC assay, OR (ii). with documented NTRK1 gene fusion (NTRK1+) including a tumor which has progressed due to NTRK1 mutation after treatment of a pan-Trk inhibitor (e.g. larotrectinib or entrectinib)
• * 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:
• • 1. Received chemotherapy having delayed toxicity within the last 14 days (six weeks for prior nitrosourea or mitomycin C).
• • 2. Received anticancer therapy with radiation, immunotherapy, and a biologic, surgery and/or tumor embolization within the past 2 weeks.
• • 3. 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.
• • 4. 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.
• • 5. Negative result on TrkA immunohistochemistry (IHC) assay (if enrolled in dose expansion cohorts).
• • 6. Known active infections including HIV disease.
• • 7. Patients with a history of chronic viral hepatitis (HBV/HCV), even if treated, or a history of cirrhotic liver secondary to any etiology (i.e. alcoholism, non-alcoholic steatohepatitis).
• • 8. Currently pregnant, nursing, or planning to become pregnant during the course of the study.
• • 9. QTcF interval ≥ 480 msec.
• • 10. Class II, III, or IV heart failure as defined by the New York Heart Association (NYHA) functional classification system.
• • 11. Acute coronary syndromes (including unstable angina), coronary angioplasty, or stenting within the past 24 weeks.
• • 12. Unstable or uncompensated respiratory, hepatic, renal, or cardiac disease that would compromise the patient's safety or interfere with assessment of the drug.
• • 13. 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.
• • 14. Known immediate or delayed hypersensitivity reaction or idiosyncrasy to the study drug, or excipients.
• • 15. Patient has had or is currently having other malignant tumors within 3 years.
• • 16. Patients have multiple factors that affect their oral medication.
• • 17. Patients have long-term unhealed wounds or fractures.
• • 18. Patients have uncontrolled pleural effusion, pericardial effusion, or ascites that still require repeated drainage.
• 19. Patients are taking the following drugs and can't stop them during the study:
• • Tylenol or medicine containing acetaminophen (paracetamol).
• • Strong cytochrome P450 3A4 (CYP3A4) inhibitors or inducers.