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

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

Tracking Information
First Submitted Date  ICMJE April 29, 2018
First Posted Date  ICMJE June 14, 2018
Last Update Posted Date July 25, 2022
Actual Study Start Date  ICMJE June 8, 2018
Estimated Primary Completion Date December 2023   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (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  ICMJE
 (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 ]
Change History
Current Secondary Outcome Measures  ICMJE
 (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  ICMJE
 (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  ICMJE Selective TrkA Inhibitor VMD-928 to Treat TrkA Overexpression Driven Solid Tumors or Lymphoma
Official Title  ICMJE 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  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE 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  ICMJE
  • 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  ICMJE Drug: VMD-928 300 mg Tablet (ongoing); 100 mg Capsule (complete)
Taken orally once daily
Study Arms  ICMJE 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

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: April 8, 2022)
74
Original Estimated Enrollment  ICMJE
 (submitted: June 1, 2018)
54
Estimated Study Completion Date  ICMJE June 2024
Estimated Primary Completion Date December 2023   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Jay Wu, PhD (510) 270-2790/ 661-6770 ext 101 OM@VMOncology.com
Contact: Liz Gaynor EGaynor@TD2inc.com
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03556228
Other Study ID Numbers  ICMJE 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  ICMJE
Plan to Share IPD: Undecided
Current Responsible Party VM Oncology, LLC
Original Responsible Party Same as current
Current Study Sponsor  ICMJE VM Oncology, LLC
Original Study Sponsor  ICMJE Same as current
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Chair: Clinical Development VM Oncology, LLC
PRS Account VM Oncology, LLC
Verification Date July 2022

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP