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Trial record 1 of 1 for:    vmd-928
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Selective TrkA Inhibitor VMD-928 to Treat TrkA Overexpression Driven Solid Tumors or Lymphoma

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03556228
Recruitment Status : Recruiting
First Posted : June 14, 2018
Last Update Posted : May 10, 2023
Sponsor:
Information provided by (Responsible Party):
VM Oncology, LLC

Study Description
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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

Condition or disease Intervention/treatment Phase
Any Solid Tumors Progressed After a Prior Immunotherapy Cervical Cancer Adenoid Cystic Carcinoma Squamous Cell Carcinoma of Head and Neck Mesothelioma Gall Bladder Cancer Thymic Carcinoma Non-Small Cell Squamous Lung Cancer Bladder Cancer Ovarian Cancer Pancreatic Cancer Colon Cancer Leiomyosarcoma Head and Neck Squamous Cell Carcinoma Thymoma Urothelial Carcinoma Drug: VMD-928 300 mg Tablet (ongoing); 100 mg Capsule (complete) Phase 1

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 Design
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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 74 participants
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
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
Actual Study Start Date : June 8, 2018
Estimated Primary Completion Date : December 2024
Estimated Study Completion Date : June 2025

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Lymphoma

Arms and Interventions
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Arm Intervention/treatment
Experimental: VMD-928 300 mg Tablet (ongoing); 100 mg Capsule (complete) Drug: VMD-928 300 mg Tablet (ongoing); 100 mg Capsule (complete)
Taken orally once daily


Outcome Measures
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Primary Outcome Measures :
  1. Number and severity of treatment-emergent AEs [ Time Frame: Within 2 cycles (each cycle is 28 days) ]

Secondary Outcome Measures :
  1. 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) ]
  2. Peak plasma concentration (Cmax) of VMD-928. [ Time Frame: On Day 1 and Day 15 of Cycle 1 (each cycle is 28 days) ]
  3. Incidence of Dose Limiting Toxicities. [ Time Frame: During the Cycle 1 (each cycle is 28 days) ]
  4. 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) ]
  5. Change in TrkA protein expression. [ Time Frame: Pre-dose and at the end of Cycle 2 (each cycle is 28 days) ]
  6. Correlation between clinical antitumor and AUC. [ Time Frame: Up to the end of the Cycle 2 (each cycle is 28 days) ]
  7. Correlation between clinical antitumor and TrkA protein expression. [ Time Frame: Up to the end of the Cycle 2 (each cycle is 28 days) ]
  8. Correlation between analgesic response and TrkA protein expression. [ Time Frame: Up to the end of the Cycle 2 (each cycle is 28 days) ]
  9. Correlation between analgesic response and AUC. [ Time Frame: Up to the end of the Cycle 2 (each cycle is 28 days) ]

Eligibility Criteria
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Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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
Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03556228


Contacts
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Contact: Jay Wu, PhD 510-270-2790, 510-661-6770 ext 101 OM@VMOncology.com
Contact: Stephanie Saathoff ssaathoff@TD2inc.com

Locations
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United States, California
City of Hope National Medical Center Active, not recruiting
Duarte, California, United States, 91010
United States, Florida
Memorial Cancer Institute at Memorial Healthcare Systems Recruiting
Pembroke Pines, Florida, United States, 33028
Contact: Shoria Martelly    954-844-9917    SMartelly@mhs.net   
Contact: Noeli Zamora    954-265-2615    NZamora@mhs.net   
Principal Investigator: Luis E Raez, MD         
United States, New Jersey
Atlantic Health System, Morristown Medical Center Recruiting
Morristown, New Jersey, United States, 07962
Contact: Salome Geene, RN, BSN, OCN    973-971-6373    salome.geene@atlantichealth.org   
Contact: Amanda Hall    973-971-5235    amandamaria.hall@atlantichealth.org   
Principal Investigator: Angela Alistar, MD         
United States, New York
Weill Cornell Medicine, Cornell University Recruiting
New York, New York, United States, 10065
Contact: Marvin Castellon    646-962-6091    mac7087@med.cornell.edu   
Contact: Jessica Wilk       jsw9043@med.cornell.edu   
Principal Investigator: Barbara Ma, M.D., M.S.         
United States, Ohio
Gabrail Cancer Center Research Recruiting
Canton, Ohio, United States, 44718
Contact: Amanda Rich    330-492-3345    arich@gabrailcancercenter.com   
Contact: Carrie Smith       csmith@gabrailcancercenter.com   
Principal Investigator: Nashat Y Gabrail, MD         
United States, Tennessee
Erlanger Health System (Hospital); University of Tennessee College of Medicine, Chattanooga Recruiting
Chattanooga, Tennessee, United States, 37403
Contact: Deborah Dyer, RN    423-778-3903    Deborah.Dyer@erlanger.org   
Principal Investigator: Stephen DePasquale, MD         
United States, Texas
The University of Texas MD Anderson Cancer Center Recruiting
Houston, Texas, United States, 77030
Contact: Madison Maas       MEMaas@mdanderson.org   
Contact: Ly M Nguyen    713-563-2169    LMNguyen1@mdanderson.org   
Principal Investigator: David S Hong, MD         
United States, Wisconsin
Medical College of Wisconsin Recruiting
Milwaukee, Wisconsin, United States, 53226
Contact: Colleen Cotter, CHES    414-805-8839    cmcotter@mcw.edu   
Contact: Gabrielle Threatt       gthreatt@mcw.edu   
Principal Investigator: Sailaja Kamaraju, MD         
Sponsors and Collaborators
VM Oncology, LLC
Investigators
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Study Chair: Clinical Development VM Oncology, LLC
More Information
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Responsible Party: VM Oncology, LLC
ClinicalTrials.gov Identifier: NCT03556228    
Other Study ID Numbers: VMO-01C
First Posted: June 14, 2018    Key Record Dates
Last Update Posted: May 10, 2023
Last Verified: May 2023
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by VM Oncology, LLC:
TrkA
NTRK1
Thymic
Mesothelioma
Head and Neck Squamous Cell Carcinoma
Ovarian
Urothelial
Squamous Cell Carcinoma of Lung (squamous NSCLC)
 Esophageal
Adenoid Cystic Carcinoma
Bladder
Cervical
Gall Bladder
Colon
Progression after anti PD-1/PD-L1 immunotherapy
Progressed after an immunotherapy
Additional relevant MeSH terms:
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Carcinoma
Carcinoma, Squamous Cell
Urinary Bladder Neoplasms
Mesothelioma
Mesothelioma, Malignant
Squamous Cell Carcinoma of Head and Neck
Leiomyosarcoma
Carcinoma, Adenoid Cystic
Thymoma
Gallbladder Neoplasms
Neoplasms by Histologic Type
Neoplasms
Lymphatic Diseases
Neoplasms, Glandular and Epithelial
Neoplasms, Squamous Cell
 Digestive System Neoplasms
Neoplasms by Site
Digestive System Diseases
Female Urogenital Diseases
Female Urogenital Diseases and Pregnancy Complications
Urogenital Diseases
Urogenital Neoplasms
Urologic Neoplasms
Urinary Bladder Diseases
Urologic Diseases
Male Urogenital Diseases
Adenoma
Neoplasms, Mesothelial
Lung Neoplasms
Respiratory Tract Neoplasms