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

Exclusion Criteria27

• 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.