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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 : April 14, 2022
Sponsor:
Information provided by (Responsible Party):
VM Oncology, LLC

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 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 PD-1/PD-L1 Immunotherapy 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.

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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 2023
Estimated Study Completion Date : June 2024


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




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) ]


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

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/ 661-6770 ext 101 OM@VMOncology.com
Contact: Liz Gaynor EGaynor@TD2inc.com

Locations
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United States, California
City of Hope National Medical Center Recruiting
Duarte, California, United States, 91010
Contact: Aruna V Parikh, MBBS CCRC    626-218-3419 ext 83419    arparikh@coh.org   
Contact: Nikeeta Prajapati, RN, BSN    626-218-0029 ext 80029      
Principal Investigator: Vincent Chung, MD         
United States, New Jersey
Atlantic Health System, Morristown Medical Center Recruiting
Morristown, New Jersey, United States, 07962
Contact: Leah Zitelli    973-971-6312    Leah.Cappadona@atlantichealth.org   
Contact: Rosemary Stefiniw    973-971-5990    Rosemary.Stefiniw@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: Alexandra Mavracick    646-962-8169    alm2074@med.cornell.edu   
Contact    (646) 962-49‬69      
Principal Investigator: Giuseppe Giaccone, MD PhD         
United States, Ohio
Gabrail Cancer Center Research Recruiting
Canton, Ohio, United States, 44718
Contact: Carrie Smith    330-492-3345 ext 208    csmith@gabrailcancercenter.com   
Contact: Amanda Rich       arich@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: Jennifer Burgess    423-778-3900    Jennifer.Burgess@erlanger.org   
Principal Investigator: Matthew Oliver, MD         
United States, Texas
The University of Texas MD Anderson Cancer Center Recruiting
Houston, Texas, United States, 77030
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: Mike Jacklin    414-805-8839    mjacklin@mcw.edu   
Contact: Holly Lemke    414-805-0261    hlemke@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
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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: April 14, 2022
Last Verified: April 2022
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 carcinoma and thymoma
Mesothelioma
Head and Neck Squamous Cell Carcinoma
Ovarian Cancer
Hepatocellular Carcinoma
Squamous Cell Carcinoma of Lung (squamous NSCLC)
Esophageal Cancer
Adenoid Cystic Carcinoma
Prostate Cancer
Cervical Cancer
Gastric Cancer
Melanoma
Acute Myeloid Leukemia
Non Hodgkin Lymphoma
Progression after PD-1/PD-L1 immunotherapy
Additional relevant MeSH terms:
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Lymphoma
Carcinoma
Prostatic Neoplasms
Leukemia, Myeloid
Melanoma
Carcinoma, Squamous Cell
Leukemia, Myeloid, Acute
Ovarian Neoplasms
Carcinoma, Hepatocellular
Stomach Neoplasms
Lymphoma, Non-Hodgkin
Uterine Cervical Neoplasms
Esophageal Neoplasms
Mesothelioma
Mesothelioma, Malignant
Squamous Cell Carcinoma of Head and Neck
Carcinoma, Adenoid Cystic
Thymoma
Lung Neoplasms
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Neoplasms, Glandular and Epithelial
Leukemia
Genital Neoplasms, Male
Urogenital Neoplasms
Neoplasms by Site