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

Primary Purpose

Any Solid Tumors Progressed After a Prior Immunotherapy, Cervical Cancer, Adenoid Cystic Carcinoma

Status
Recruiting
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
VMD-928 300 mg Tablet (ongoing); 100 mg Capsule (complete)
Sponsored by
VM Oncology, LLC
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Any Solid Tumors Progressed After a Prior Immunotherapy focused on measuring 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

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • City of Hope National Medical Center
  • Memorial Cancer Institute at Memorial Healthcare SystemsRecruiting
  • Atlantic Health System, Morristown Medical CenterRecruiting
  • Weill Cornell Medicine, Cornell UniversityRecruiting
  • Gabrail Cancer Center ResearchRecruiting
  • Erlanger Health System (Hospital); University of Tennessee College of Medicine, Chattanooga
  • The University of Texas MD Anderson Cancer CenterRecruiting
  • Medical College of WisconsinRecruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

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

Arm Description

Outcomes

Primary Outcome Measures

Number and severity of treatment-emergent AEs

Secondary Outcome Measures

Area under the plasma concentration versus time curve (AUC) of VMD-928.
Peak plasma concentration (Cmax) of VMD-928.
Incidence of Dose Limiting Toxicities.
Analgesic response as defined by the Brief Pain Inventory (BPI).
Change in TrkA protein expression.
Correlation between clinical antitumor and AUC.
Correlation between clinical antitumor and TrkA protein expression.
Correlation between analgesic response and TrkA protein expression.
Correlation between analgesic response and AUC.

Full Information

First Posted
April 29, 2018
Last Updated
October 13, 2023
Sponsor
VM Oncology, LLC
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1. Study Identification

Unique Protocol Identification Number
NCT03556228
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
Study Type
Interventional

2. Study Status

Record Verification Date
October 2023
Overall Recruitment Status
Recruiting
Study Start Date
June 8, 2018 (Actual)
Primary Completion Date
December 2024 (Anticipated)
Study Completion Date
June 2025 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
VM Oncology, LLC

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
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
Keywords
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

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Sequential Assignment
Model Description
Dose Escalation: Tablet formulation (ongoing); Capsule formulation (complete) Cohort Expansion with RP2D;
Masking
None (Open Label)
Allocation
N/A
Enrollment
74 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
VMD-928 300 mg Tablet (ongoing); 100 mg Capsule (complete)
Arm Type
Experimental
Intervention Type
Drug
Intervention Name(s)
VMD-928 300 mg Tablet (ongoing); 100 mg Capsule (complete)
Intervention Description
Taken orally once daily
Primary Outcome Measure Information:
Title
Number and severity of treatment-emergent AEs
Time Frame
Within 2 cycles (each cycle is 28 days)
Secondary Outcome Measure Information:
Title
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)
Title
Peak plasma concentration (Cmax) of VMD-928.
Time Frame
On Day 1 and Day 15 of Cycle 1 (each cycle is 28 days)
Title
Incidence of Dose Limiting Toxicities.
Time Frame
During the Cycle 1 (each cycle is 28 days)
Title
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)
Title
Change in TrkA protein expression.
Time Frame
Pre-dose and at the end of Cycle 2 (each cycle is 28 days)
Title
Correlation between clinical antitumor and AUC.
Time Frame
Up to the end of the Cycle 2 (each cycle is 28 days)
Title
Correlation between clinical antitumor and TrkA protein expression.
Time Frame
Up to the end of the Cycle 2 (each cycle is 28 days)
Title
Correlation between analgesic response and TrkA protein expression.
Time Frame
Up to the end of the Cycle 2 (each cycle is 28 days)
Title
Correlation between analgesic response and AUC.
Time Frame
Up to the end of the Cycle 2 (each cycle is 28 days)

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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: Absolute neutrophil count ≥1.5x10^9/L Hemoglobin ≥9g/dL Platelets ≥100x10^9/L PT/INR, PTT ≤1.5xULN Total bilirubin ≤1.5x ULN AST, ALT ≤2.5xULN Creatinine ≤1.2xULN for age, weight Calculated creatinine clearance or 24h urine creatinine clearance ≥60mL/min Key Exclusion Criteria: Received chemotherapy having delayed toxicity within the last 14 days (six weeks for prior nitrosourea or mitomycin C). Received anticancer therapy with radiation, immunotherapy, and a biologic, surgery and/or tumor embolization within the past 2 weeks. 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. 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. Negative result on TrkA immunohistochemistry (IHC) assay. Known active infections including HIV disease. 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). Currently pregnant, nursing, or planning to become pregnant during the course of the study. QTcF interval ≥ 480 msec. Class II, III, or IV heart failure as defined by the New York Heart Association (NYHA) functional classification system. Acute coronary syndromes (including unstable angina), coronary angioplasty, or stenting within the past 24 weeks. Unstable or uncompensated respiratory, hepatic, renal, or cardiac disease that would compromise the patient's safety or interfere with assessment of the drug. 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. Known immediate or delayed hypersensitivity reaction or idiosyncrasy to the study drug, or excipients
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Jay Wu, PhD
Phone
510-270-2790, 510-661-6770
Ext
101
Email
OM@VMOncology.com
First Name & Middle Initial & Last Name or Official Title & Degree
Stephanie Saathoff
Email
ssaathoff@TD2inc.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Clinical Development
Organizational Affiliation
VM Oncology, LLC
Official's Role
Study Chair
Facility Information:
Facility Name
City of Hope National Medical Center
City
Duarte
State/Province
California
ZIP/Postal Code
91010
Country
United States
Individual Site Status
Active, not recruiting
Facility Name
Memorial Cancer Institute at Memorial Healthcare Systems
City
Pembroke Pines
State/Province
Florida
ZIP/Postal Code
33028
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Shoria Martelly
Phone
954-844-9917
Email
SMartelly@mhs.net
First Name & Middle Initial & Last Name & Degree
Noeli Zamora
Phone
954-265-2615
Email
NZamora@mhs.net
First Name & Middle Initial & Last Name & Degree
Luis E Raez, MD
Facility Name
Atlantic Health System, Morristown Medical Center
City
Morristown
State/Province
New Jersey
ZIP/Postal Code
07962
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Salome Geene, RN, BSN, OCN
Phone
973-971-6373
Email
salome.geene@atlantichealth.org
First Name & Middle Initial & Last Name & Degree
Amanda Hall
Phone
973-971-5235
Email
amandamaria.hall@atlantichealth.org
First Name & Middle Initial & Last Name & Degree
Angela Alistar, MD
Facility Name
Weill Cornell Medicine, Cornell University
City
New York
State/Province
New York
ZIP/Postal Code
10065
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Marvin Castellon
Phone
646-962-6091
Email
mac7087@med.cornell.edu
First Name & Middle Initial & Last Name & Degree
Jessica Wilk
Email
jsw9043@med.cornell.edu
First Name & Middle Initial & Last Name & Degree
Barbara Ma, M.D., M.S.
Facility Name
Gabrail Cancer Center Research
City
Canton
State/Province
Ohio
ZIP/Postal Code
44718
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Amanda Rich
Phone
330-492-3345
Email
arich@gabrailcancercenter.com
First Name & Middle Initial & Last Name & Degree
Carrie Smith
Email
csmith@gabrailcancercenter.com
First Name & Middle Initial & Last Name & Degree
Nashat Y Gabrail, MD
Facility Name
Erlanger Health System (Hospital); University of Tennessee College of Medicine, Chattanooga
City
Chattanooga
State/Province
Tennessee
ZIP/Postal Code
37403
Country
United States
Individual Site Status
Active, not recruiting
Facility Name
The University of Texas MD Anderson Cancer Center
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Madison Maas
Email
MEMaas@mdanderson.org
First Name & Middle Initial & Last Name & Degree
Ly M Nguyen
Phone
713-563-2169
Email
LMNguyen1@mdanderson.org
First Name & Middle Initial & Last Name & Degree
David S Hong, MD
Facility Name
Medical College of Wisconsin
City
Milwaukee
State/Province
Wisconsin
ZIP/Postal Code
53226
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Colleen Cotter, CHES
Phone
414-805-8839
Email
cmcotter@mcw.edu
First Name & Middle Initial & Last Name & Degree
Gabrielle Threatt
Email
gthreatt@mcw.edu
First Name & Middle Initial & Last Name & Degree
Sailaja Kamaraju, MD

12. IPD Sharing Statement

Plan to Share IPD
Undecided

Learn more about this trial

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

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