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

• ClinicalTrials.gov Identifier: NCT03556228
• Recruitment Status: Recruiting
• First Posted: June 14, 2018
• Last Update Posted: July 25, 2022
• Sponsor: VM Oncology, LLC
• Information provided by (Responsible Party): VM Oncology, LLC

Tracking Information

• First Submitted Date: April 29, 2018
• First Posted Date: June 14, 2018
• Last Update Posted Date: July 25, 2022
• Actual Study Start Date: June 8, 2018
• Estimated Primary Completion Date: December 2023 (Final data collection date for primary outcome measure)
• Current Primary Outcome Measures (submitted: April 8, 2022): Number and severity of treatment-emergent AEs [ Time Frame: Within 2 cycles (each cycle is 28 days) ]
• Original Primary Outcome Measures (submitted: June 1, 2018): Number and severity of treatment-emergent AEs [ Time Frame: Within two months of the first VMD-928 dose for each patient ]

Current Secondary Outcome Measures (submitted: April 8, 2022)

• Area under the plasma concentration versus time curve (AUC) of VMD-928. [ Time Frame: On Day 1 and Day 15 of Cycle 1 (each cycle is 28 days) ]
• Peak plasma concentration (Cmax) of VMD-928. [ Time Frame: On Day 1 and Day 15 of Cycle 1 (each cycle is 28 days) ]
• Incidence of Dose Limiting Toxicities. [ Time Frame: During the Cycle 1 (each cycle is 28 days) ]
• Analgesic response as defined by the Brief Pain Inventory (BPI). [ Time Frame: On Day 1 and Day 15 of Cycle 1 (each cycle is 28 days) ]
• Change in TrkA protein expression. [ Time Frame: Pre-dose and at the end of Cycle 2 (each cycle is 28 days) ]
• Correlation between clinical antitumor and AUC. [ Time Frame: Up to the end of the Cycle 2 (each cycle is 28 days) ]
• Correlation between clinical antitumor and TrkA protein expression. [ Time Frame: Up to the end of the Cycle 2 (each cycle is 28 days) ]
• Correlation between analgesic response and TrkA protein expression. [ Time Frame: Up to the end of the Cycle 2 (each cycle is 28 days) ]
• Correlation between analgesic response and AUC. [ Time Frame: Up to the end of the Cycle 2 (each cycle is 28 days) ]

Original Secondary Outcome Measures (submitted: June 1, 2018)

• Area under the plasma concentration versus time curve (AUC) of VMD-928. [ Time Frame: Two to three months after starting treatment for each patient [Estimated] ]
• Peak plasma concentration (Cmax) of VMD-928. [ Time Frame: Two to three months after starting treatment for each patient [Estimated] ]
• Incidence of Dose Limiting Toxicities. [ Time Frame: Within two months of the first VMD-928 dose for each patient ]
• Analgesic response as defined by the Brief Pain Inventory (BPI). [ Time Frame: Within two months after starting treatment for each patient [Estimated] ]
• Change in p-TrkA protein expression. [ Time Frame: Within two months after starting treatment for each patient [Estimated] ]
• Correlation between clinical antitumor and AUC. [ Time Frame: Six to eight months after starting treatment for each patient [Estimated] ]
• Correlation between clinical antitumor and p-TrkA inhibition. [ Time Frame: Six to eight months after starting treatment for each patient [Estimated] ]
• Correlation between analgesic response and p-TrkA inhibition. [ Time Frame: Six to eight months after starting treatment for each patient [Estimated] ]
• Correlation between analgesic response and AUC. [ Time Frame: Six to eight months after starting treatment for each patient [Estimated] ]

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Selective TrkA Inhibitor VMD-928 to Treat TrkA Overexpression Driven Solid Tumors or Lymphoma
• Official Title: 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
• Brief Summary: 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
• Detailed Description: This is an open-label, Phase I, FTIH, multiple-dose, dose-escalation and cohort expansion multi-center study conducted in three parts to identify a safe and pharmacologically active dose and regimen for VMD-928 monotherapy, which can be implemented in Phase 2 studies (the RP2D). The regimen will be identified using an adaptive design, multiple-ascending dose study in cancer patients. To conserve patients in the lower dose cohorts, dose escalation will begin with an accelerated titration scheme. A second part of the study will assess antitumor activity at the RP2D. The third part of the study will collect tumor samples before and after treatment to assess biological activity.
• Study Type: Interventional
• Study Phase: Phase 1

Study Design

Allocation: N/A
Intervention Model: Sequential Assignment
Intervention Model Description:

• Dose Escalation: Tablet formulation (ongoing); Capsule formulation (complete)
• Cohort Expansion with RP2D;

Masking: None (Open Label)
Primary Purpose: Treatment

Condition

• Any Solid Tumors
• Mesothelioma
• Head and Neck Squamous Cell Carcinoma
• Ovarian Cancer
• Hepatocellular Carcinoma
• Squamous Cell Carcinoma of Lung
• Esophageal Cancer
• Adenoid Cystic Carcinoma
• Prostate Cancer
• Cervical Cancer
• Gastric Cancer
• Melanoma
• Acute Myeloid Leukemia
• Non Hodgkin Lymphoma
• Thymic Carcinoma and Thymoma
• Progressor of Anti PD-1/PD-L1 Immunotherapy

Intervention

Drug: VMD-928 300 mg Tablet (ongoing); 100 mg Capsule (complete)

Taken orally once daily

Study Arms

Experimental: VMD-928 300 mg Tablet (ongoing); 100 mg Capsule (complete)

Intervention: Drug: VMD-928 300 mg Tablet (ongoing); 100 mg Capsule (complete)

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: April 8, 2022): 74
• Original Estimated Enrollment (submitted: June 1, 2018): 54
• Estimated Study Completion Date: June 2024
• Estimated Primary Completion Date: December 2023 (Final data collection date for primary outcome measure)

Eligibility Criteria

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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: Jay Wu, PhD; (510) 270-2790/ 661-6770 ext 101; OM@VMOncology.com

Contact: Liz Gaynor; EGaynor@TD2inc.com

• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT03556228
• Other Study ID Numbers: VMO-01C
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: Undecided

• Current Responsible Party: VM Oncology, LLC
• Original Responsible Party: Same as current
• Current Study Sponsor: VM Oncology, LLC
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Study Chair: Clinical Development; VM Oncology, LLC

• PRS Account: VM Oncology, LLC
• Verification Date: July 2022