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
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
• 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:
‣ Absolute neutrophil count ≥1.5x10\^9/L
⁃ Hemoglobin ≥9g/dL
⁃ Platelets ≥100x10\^9/L
⁃ PT/INR, PTT ≤1.5xULN
⁃ Total bilirubin ≤1.5x ULN
⁃ AST, ALT ≤2.5xULN
⁃ Creatinine ≤1.2xULN for age, weight
⁃ Calculated creatinine clearance or 24h urine creatinine clearance ≥60mL/min