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

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

INTRODUCTION

  • Org Study ID: VMO-01C
  • Secondary ID: N/A
  • NCT ID: NCT03556228
  • Sponsor: 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

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.

  • Overall Status
    Recruiting
  • Start Date
    June 8, 2018
  • Phase
    Phase 1
  • Study Type
    Interventional

PRIMARY OUTCOMES

Primary Outcome 1 - Measure:

Primary Outcome 1 - Timeframe: N/A

CONDITION

  • Head and Neck Carcinoma
  • Adenoid Cystic Carcinoma
  • Cervical Cancer
  • Breast Cancer
  • Lung Cancer
  • Non-Small Cell Lung Cancer
  • Mesothelioma
  • Thymic Carcinoma
  • Bladder Cancer
  • Ovarian Cancer
  • Pancreatic Cancer
  • Sarcoma
  • Any Solid Tumors Progressed After a Prior Immunotherapy

ELIGIBILITY

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

Gender: All

Minimum Age: 18 Years

Maximum Age: N/A

Healthy Volunteers: No

OFFICIAL INFORMATION

Name: Clinical Development

Role: Study Chair

Affiliation: VM Oncology, LLC

Overall Contact

Name: Jay Wu, PhD, Stephanie Saathoff

Phone: 510-270-2790, 510-661-6770

Email: OM@VMOncology.com, ssaathoff@TD2inc.com

LOCATION

Facility Status Contact
Facility: Memorial Cancer Institute at Memorial Healthcare Systems
Pembroke Pines, Florida 33028
United States
Status: Recruiting Contact: Contact
Shoria Martelly
954-844-9917
SMartelly@mhs.net

Contact
Noeli Zamora
954-265-2615
NZamora@mhs.net

Principal Investigator
Luis E Raez, MD

Facility: Atlantic Health System, Morristown Medical Center
Morristown, New Jersey 07962
United States
Status: Recruiting Contact: 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

Facility: Weill Cornell Medicine, Cornell University
New York, New York 10065
United States
Status: Recruiting Contact: 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.

Facility: Gabrail Cancer Center Research
Canton, Ohio 44718
United States
Status: Recruiting Contact: Contact
Amanda Rich
330-492-3345
arich@gabrailcancercenter.com

Contact
Carrie Smith
csmith@gabrailcancercenter.com

Principal Investigator
Nashat Y Gabrail, MD

Facility: The University of Texas MD Anderson Cancer Center
Houston, Texas 77030
United States
Status: Recruiting Contact: Contact
Madison Maas
MEMaas@mdanderson.org

Contact
Ly M Nguyen
713-563-2169
LMNguyen1@mdanderson.org

Principal Investigator
David S Hong, MD

Facility: Medical College of Wisconsin
Milwaukee, Wisconsin 53226
United States
Status: Recruiting Contact: Contact
Colleen Cotter, CHES
414-805-8839
cmcotter@mcw.edu

Contact
Gabrielle Threatt
gthreatt@mcw.edu

Principal Investigator
Sailaja Kamaraju, MD