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Oral TrkA Inhibitor VMD-928 for Treatment of Advanced Adult Solid Tumors or Lymphoma

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ClinicalTrials.gov Identifier: NCT03556228
Recruitment Status : Recruiting
First Posted : June 14, 2018
Last Update Posted : March 15, 2021
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
Thymic Carcinoma and Thymoma 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 Drug: VMD-928 300 mg Tablets or 100 mg Capsules 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 : 54 participants
Allocation: N/A
Intervention Model: Sequential Assignment
Intervention Model Description:
  • Part 1, Dose Escalation: Identify the RP2D (complete);
  • Parts 2-4, Cohort Expansion with RP2D (ongoing);
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 : June 2022
Estimated Study Completion Date : December 2022


Arm Intervention/treatment
Experimental: VMD-928 300 mg Tablet or 100 mg Capsule Drug: VMD-928 300 mg Tablets or 100 mg Capsules
Taken orally once daily




Primary Outcome Measures :
  1. Number and severity of treatment-emergent AEs [ Time Frame: Within two months of the first VMD-928 dose for each patient ]

Secondary Outcome Measures :
  1. 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] ]
  2. Peak plasma concentration (Cmax) of VMD-928. [ Time Frame: Two to three months after starting treatment for each patient [Estimated] ]
  3. Incidence of Dose Limiting Toxicities. [ Time Frame: Within two months of the first VMD-928 dose for each patient ]
  4. Analgesic response as defined by the Brief Pain Inventory (BPI). [ Time Frame: Within two months after starting treatment for each patient [Estimated] ]
  5. Change in p-TrkA protein expression. [ Time Frame: Pre-dose and within two months after starting treatment for each patient [Estimated] ]
  6. Correlation between clinical antitumor and AUC. [ Time Frame: Six to eight months after starting treatment for each patient [Estimated] ]
  7. Correlation between clinical antitumor and p-TrkA inhibition. [ Time Frame: Six to eight months after starting treatment for each patient [Estimated] ]
  8. Correlation between analgesic response and p-TrkA inhibition. [ Time Frame: Six to eight months after starting treatment for each patient [Estimated] ]
  9. Correlation between analgesic response and AUC. [ Time Frame: Six to eight months after starting treatment for each patient [Estimated] ]


Information from the National Library of Medicine

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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

Part-1 Dose Escalation [Key Inclusion]:

  • Histologically or cytologically confirmed diagnosis of solid tumor malignancy or lymphoma that is not responsive to standard therapies, are unfit for standard chemotherapy or for which there is no approved or curative therapy.
  • ECOG score of 0 or 1.
  • Able to swallow and retain oral medication.
  • Adequate organ system function.

Parts 2-4 Cohort Expansion Only [Key Inclusion]:

  • Part 1 inclusion criteria.
  • 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, AND have a tumor or tumor type in one of the following categories:

    (i). Tumors showing a response or stable disease after at least 2 cycles of VMD-928 during Part 1;

(ii). Tumor types associated with high TrkA protein overexpression, i.e.:

  • Thymic carcinoma and thymoma
  • Mesothelioma
  • Head and neck squamous cell carcinoma (HNSCC)
  • Ovarian cancer (especially serous)
  • Hepatocellular carcinoma
  • Squamous cell carcinoma of lung (squamous NSCLC)
  • Esophageal cancer
  • Adenoid cystic carcinoma
  • Prostate cancer
  • Cervical cancer
  • Gastric cancer
  • Melanoma
  • Acute myeloid leukemia
  • Pancreatic carcinoma
  • Non-Hodgkins' lymphoma

(iii). Tumors with documented NTRK1 gene fusions or amplifications, or TrkA protein overexpression, or a tumor which has progressed due to NTRK1 mutation after treatment of a pan-Trk inhibitor (e.g. larotrectinib or entrectinib)

Part 3 Pharmacodynamic Activity only (Eligible subjects in Part 2 may enroll in Part 3):

  • Part-2 inclusion criteria.
  • Tumor with readily accessible lesion that is amenable to biopsy and consent to pre-and post-dose biopsy.

Part 4 Exploratory Comparative PK of Tablet vs. Capsule Formulations only (Eligible subjects in Part 2 or 3 will be encouraged to enroll in Part 4)

Key Exclusion Criteria (Parts 1-4):

  1. Received chemotherapy having delayed toxicity within the last 21 days (six weeks for prior nitrosourea or mitomycin C).
  2. Received anticancer therapy with radiation, immunotherapy, a biologic, surgery and/or tumor embolization within the past 2 weeks.
  3. Received an investigational anti-cancer drug within 21 days or 5 half-lives of the investigational agent prior, whichever is longer, to the first dose of VMD-928.
  4. Unresolved toxicity from previous anti-cancer therapy ≥ CTCAE Grade 1 (except alopecia or anemia) unless agreed to by both the Investigator and Sponsor.
  5. Negative result on TrkA-specific or pan-Trk IHC assay (Parts 2-4 only).
  6. Known active infections including HIV disease.
  7. Currently pregnant, nursing, or planning to become pregnant during the course of the study.
  8. QTcF interval ≥ 480 msec.
  9. Class II, III, or IV heart failure as defined by the New York Heart Association (NYHA) functional classification system.
  10. Acute coronary syndromes (including unstable angina), coronary angioplasty, or stenting within the past 24 weeks.
  11. Unstable or uncompensated respiratory, hepatic, renal, or cardiac disease that would compromise the patient's safety or interfere with assessment of the drug.
  12. Psychological, familial, sociological, geographical or other concurrent conditions that would interfere with safety evaluation, limit the subject's ability to follow the procedures in the protocol or otherwise jeopardize compliance with the protocol. Subjects with uncontrolled major depression, bipolar disorder, or severe anxiety disorder are excluded.

    Key Exclusion Criteria (For Parts 1 and 4 only):

  13. Any current medical condition that would alter the absorption, distribution, metabolism or excretion of VMD-928 including but not limited to:

    • Severe uncontrolled nausea or vomiting
    • Severe uncontrolled diarrhea
    • With a history of short bowel syndrome
    • Clinically diagnosed malabsorption secondary to bowel resection

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 510-661-6770 ext 101 OM@VMOncology.com
Contact: Liz Gaynor; Cameron Wright 602-358-8344; 602-358-8341 egaynor@td2inc.com; cwright@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, M.B.B.S. 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    gig4001@med.cornell.edu   
Principal Investigator: Giuseppe Giaccone, MD PhD         
United States, Texas
The University of Texas MD Anderson Cancer Center Recruiting
Houston, Texas, United States, 77030
Contact: Mianen Sun, PhD    832-540-0311    msun4@mdanderson.org   
Contact    713-563-1930    dshong@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 Director: Peg Fletcher, MD PhD MedAssessment
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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: March 15, 2021
Last Verified: March 2021
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
Additional relevant MeSH terms:
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Lymphoma
Carcinoma
Prostatic Neoplasms
Melanoma
Carcinoma, Squamous Cell
Leukemia, Myeloid, Acute
Ovarian Neoplasms
Carcinoma, Hepatocellular
Lymphoma, Non-Hodgkin
Stomach Neoplasms
Uterine Cervical Neoplasms
Esophageal Neoplasms
Mesothelioma
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
Prostatic Diseases
Leukemia, Myeloid