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

PRIMARY OUTCOMES

Primary Outcome 1 - Measure:

Primary Outcome 1 - Timeframe: N/A

CONDITION

• Head and Neck Carcinoma
• Adenoid Cystic Carcinoma
• Cervical Cancer
• Breast Cancer
• Lung Cancer
• Non-Small Cell Lung Cancer
• Mesothelioma
• Thymic Carcinoma
• Bladder Cancer
• Ovarian Cancer
• Pancreatic Cancer
• Sarcoma
• Any Solid Tumors Progressed After a Prior Immunotherapy

ELIGIBILITY

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.

- * Subjects must have a tumor:
(i). with TrkA protein overexpression in the validated TrkA IHC assay, OR (ii). with documented NTRK1 gene fusion, or 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.

- 6. Known active infections including HIV disease.

- 7. Patients with a history of chronic viral hepatitis (HBV/HCV) 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

Gender: All

Minimum Age: 18 Years

Maximum Age: N/A

Healthy Volunteers: No

OFFICIAL INFORMATION

Name: Clinical Development

Role: Study Chair

Affiliation: VM Oncology, LLC

Overall Contact

Name: Jay Wu, PhD, Stephanie Saathoff

Phone: 510-270-2790, 510-661-6770

Email: OM@VMOncology.com, ssaathoff@TD2inc.com

LOCATION