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

Breast Cancer Clinical Trial

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03556228
• Other study ID #: VMO-01C
• Status: Recruiting
• Phase: Phase 1
• Start date: June 8, 2018
• Est. completion date: December 2025

Study information

• Verified date: April 2024
• Source: VM Oncology, LLC
• Contact: Jay Wu, PhD
• Phone: 510-270-2790, 510-661-6770
• Email: OM[@]VMOncology.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 74
• Est. completion date: December 2025
• Est. primary completion date: June 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

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

Related Conditions & MeSH terms

• Adenoid Cystic Carcinoma
• Bladder Cancer
• Breast Cancer
• Carcinoma
• Carcinoma, Adenoid Cystic
• Carcinoma, Non-Small-Cell Lung
• Cervical Cancer
• Head and Neck Carcinoma
• Lung Cancer
• Lung Neoplasms
• Mesothelioma
• Mesothelioma, Malignant
• Non-Small Cell Lung Cancer
• Ovarian Cancer
• Pancreatic Cancer
• Sarcoma
• Thymic Carcinoma
• Thymoma
• Urinary Bladder Neoplasms
• Uterine Cervical Neoplasms

Intervention

Drug:
• VMD-928 300 mg Tablet (ongoing); 100 mg Capsule (complete)
Taken orally once daily

Locations

Country	Name	City	State
Puerto Rico	PanOncology Trials, Hospital Oncologico - Puerto Rico Medical Center, Río Piedras	San Juan
United States	Gabrail Cancer Center Research	Canton	Ohio
United States	Erlanger Health System (Hospital); University of Tennessee College of Medicine, Chattanooga	Chattanooga	Tennessee
United States	City of Hope National Medical Center	Duarte	California
United States	The University of Texas MD Anderson Cancer Center	Houston	Texas
United States	Cayuga Medical Center	Ithaca	New York
United States	Medical College of Wisconsin	Milwaukee	Wisconsin
United States	Atlantic Health System, Morristown Medical Center	Morristown	New Jersey
United States	Weill Cornell Medicine, Cornell University	New York	New York
United States	Memorial Cancer Institute at Memorial Healthcare Systems	Pembroke Pines	Florida

Sponsors (1)

Lead Sponsor	Collaborator
VM Oncology, LLC

Countries where clinical trial is conducted

United States,  Puerto Rico, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number and severity of treatment-emergent AEs		Within 2 cycles (each cycle is 28 days)
Secondary	Area under the plasma concentration versus time curve (AUC) of VMD-928.		On Day 1 and Day 15 of Cycle 1 (each cycle is 28 days)
Secondary	Peak plasma concentration (Cmax) of VMD-928.		On Day 1 and Day 15 of Cycle 1 (each cycle is 28 days)
Secondary	Incidence of Dose Limiting Toxicities.		During the Cycle 1 (each cycle is 28 days)
Secondary	Analgesic response as defined by the Brief Pain Inventory (BPI).		On Day 1 and Day 15 of Cycle 1 (each cycle is 28 days)
Secondary	Change in TrkA protein expression.		Pre-dose and at the end of Cycle 2 (each cycle is 28 days)
Secondary	Correlation between clinical antitumor and AUC.		Up to the end of the Cycle 2 (each cycle is 28 days)
Secondary	Correlation between clinical antitumor and TrkA protein expression.		Up to the end of the Cycle 2 (each cycle is 28 days)
Secondary	Correlation between analgesic response and TrkA protein expression.		Up to the end of the Cycle 2 (each cycle is 28 days)
Secondary	Correlation between analgesic response and AUC.		Up to the end of the Cycle 2 (each cycle is 28 days)