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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: Number and severity of treatment-emergent AEs

Primary Outcome 1 - Timeframe: Within 2 cycles (each cycle is 28 days)

CONDITION

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

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, except with prior documented NTRK+.

- * Subjects must have a tumor:
(i). with TrkA protein overexpression (TrkA+) in the validated TrkA IHC assay, OR (ii). with documented NTRK1 gene fusion (NTRK1+) including 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 (if enrolled in dose expansion cohorts).

- 6. Known active infections including HIV disease.

- 7. Patients with a history of chronic viral hepatitis (HBV/HCV), even if treated, 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.

- 15. Patient has had or is currently having other malignant tumors within 3 years.

- 16. Patients have multiple factors that affect their oral medication.

- 17. Patients have long-term unhealed wounds or fractures.

- 18. Patients have uncontrolled pleural effusion, pericardial effusion, or ascites that still require repeated drainage.

- 19. Patients are taking the following drugs and can't stop them during the study:
* Tylenol or medicine containing acetaminophen (paracetamol).

- * Strong cytochrome P450 3A4 (CYP3A4) inhibitors or inducers.

Gender: All

Minimum Age: 18 Years

Maximum Age: N/A

Healthy Volunteers: No

OFFICIAL INFORMATION

Name: Clinical Development

Role: Study Chair

Affiliation: VM Oncology

Overall Contact

Name: Jay Wu, PhD, Krishna Patel; Stephanie Saathoff

Phone: 1-510-270-2790

Email: [email protected], [email protected]; [email protected]

LOCATION

Facility Status Contact
Facility: Providence Medical Foundation
Santa Rosa, California 95403
United States
Status: Recruiting Contact: Contact
Melissa Ulrich
707-521-3833
[email protected]

Contact
Sam Hansen
707-521-3829
[email protected]

Principal Investigator
Ian C Anderson, MD

Facility: Hartford Hospital
Hartford, Connecticut 06102
United States
Status: Recruiting Contact: Contact
Hayley Yackel
860-972-5518
[email protected]

Contact
Christopher Sampson
860-972-5026
[email protected]

Principal Investigator
Jaykumar Thumar, MD

Facility: Memorial Cancer Institute at Memorial Healthcare Systems
Pembroke Pines, Florida 33028
United States
Status: Recruiting Contact: Contact
Shoria Martelly
954-844-9917
[email protected]

Contact
Ines Padron Cubillan
954-844-8737
[email protected]

Principal Investigator
Luis E Raez, MD

Facility: Englewood Hospital and Medical Center
Englewood, New Jersey 07631
United States
Status: Recruiting Contact: Contact
William Dippolito
201-608-2572
[email protected]

Contact
Dara Herman
[email protected]

Principal Investigator
Minaxi Jhawer, MD

Facility: Summit Medical Group
Florham Park, New Jersey 07932
United States
Status: Recruiting Contact: Contact
Michelle Mackenzie
973-436-1755
[email protected]

Contact
Romilda Moreira
973-436-1748
[email protected]

Principal Investigator
David Gallinson, DO

Facility: Atlantic Health System, Morristown Medical Center
Morristown, New Jersey 07962
United States
Status: Recruiting Contact: Contact
Tracey Hilden, RN, BSN, OCN
973-971-7889
[email protected]

Contact
Salome Geene
973-971-6373
[email protected]

Principal Investigator
Angela Alistar, MD

Facility: Presbyterian Kaseman Hospital
Albuquerque, New Mexico 87110
United States
Status: Recruiting Contact: Contact
Matthew Widdows, CCRC
505-559-6089
[email protected]

Contact
Monique Robertson
505-559-6143
[email protected]

Principal Investigator
Ethan Binder, MD

Facility: Cayuga Medical Center
Ithaca, New York 14850
United States
Status: Recruiting Contact: Contact
Danielle Rao, DMD
301-693-5704
[email protected]

Contact
Betty Haverlock
607-252-3939
[email protected]

Principal Investigator
Anthony Mato, MD

Facility: Weill Cornell Medicine, Cornell University
New York, New York 10065
United States
Status: Recruiting Contact: Contact
Marvin Castellon
646-962-6091
[email protected]

Contact
Jessica Wilk
[email protected]

Principal Investigator
Barbara Ma, M.D., M.S.

Facility: Taylor Cancer Research Center
Maumee, Ohio 43537
United States
Status: Recruiting Contact: Contact
Stephanie Ambrose, RN, BSN, CCRC
567.402.4502
[email protected]

Contact
Jessica Obarski, RN, CCRC
567.402.4503
[email protected]

Principal Investigator
John J Nemunaitis, MD

Facility: Cancer Care Associates of York
York, Pennsylvania 17403
United States
Status: Recruiting Contact: Contact
Katelyn Bean
1-717-741-9229
[email protected]

Contact
Jennifer Stough
1-717-741-9229
[email protected]

Principal Investigator
Chanh Huynh, MD

Facility: The University of Texas MD Anderson Cancer Center
Houston, Texas 77030
United States
Status: Recruiting Contact: Contact
Madison Maas
[email protected]

Contact
Ly M Nguyen
713-563-2169
[email protected]

Principal Investigator
David S Hong, MD

Facility: Utah Cancer Specialists
Salt Lake City, Utah 84106
United States
Status: Recruiting Contact: Contact
Angela Nuttall
801-269-0231
[email protected]

Contact
Angie Sonntag
801-267-5605
[email protected]; [email protected]

Principal Investigator
Stephan DiSean Kendall, MD