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

This is an open-label, dose-escalation (Phase 1) and expansion (Phase 2) multi-center study conducted in five parts to identify the safe and pharmacologically active doses (MTD and/orRP2D) and regimen for oral VMD-928 monotherapy and in combination with a PD-1 inhibitor, pembrolizumab in cancer patients. An immunohistochemistry (IHC) assay specific for detecting TrkA protein in tumor tissue samples has been validated and is being used to detect TrkA protein expressions in patient tumor tissue samples at Pre-screening. The study is currently focusing on the top 5 solid tumor with the highest TrkA protein overexpression are: Head and Neck Cancers (HNC), Esophageal cancer, Lung cancers, Mesothelioma, and Pancreatic Cancer.

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.