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

Key Inclusion Criteria:

• Histologically or cytologically confirmed diagnosis of any type of solid tumormalignancy or lymphoma that is not responsive to standard therapies or hadprogressed following standard therapy and for which there is no approved or curativetherapy. Additionally, patients must not be candidates for or have exhaustedregimens known to provide clinical benefit, including hematopoietic stem celltransplantation 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 totumor tissue sampling prior to the first dose, that is sufficient for IHC analysisof 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 hasprogressed 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 forprior nitrosourea or mitomycin C).

2. Received anticancer therapy with radiation, immunotherapy, and a biologic, surgeryand/or tumor embolization within the past 2 weeks.

3. Received an investigational anticancer drug within 14 days or 5 half-lives of theinvestigational agent, whichever is longer, prior to the first dose of VMD-928. Anyexceptions 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 andthe Investigator.

5. Negative result on TrkA immunohistochemistry (IHC) assay (if enrolled in doseexpansion cohorts).

6. Known active infections including HIV disease.

7. Patients with a history of chronic viral hepatitis (HBV/HCV), even if treated, or ahistory of cirrhotic liver secondary to any etiology (i.e. alcoholism, non-alcoholicsteatohepatitis).

8. Currently pregnant, nursing, or planning to become pregnant during the course of thestudy.

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, orstenting within the past 24 weeks.

12. Unstable or uncompensated respiratory, hepatic, renal, or cardiac disease that wouldcompromise the patient's safety or interfere with assessment of the drug.

13. Psychological, familial, sociological, geographical, or other concurrent conditionsthat would interfere with safety evaluation, limit the patient's ability to followthe procedures in the protocol or otherwise jeopardize compliance with the protocol.Patients with uncontrolled major depression, bipolar disorder, or severe anxietydisorder are excluded.

14. Known immediate or delayed hypersensitivity reaction or idiosyncrasy to the studydrug, 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 thatstill 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.