VMD-928 Monotherapy and in Combination With Pembrolizumab to Treat TrkA Overexpression Driven Solid Tumors or Lymphoma

NCT03556228 | Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: VMO-01C
• Study Type: interventional
• Target: 242
• Locations: 2 countries
• Sites: 15

Brief Summary

This is a multicenter, open-label, Phase 1/2 study of orally administered VMD-928 monotherapy and in combination with pembrolizumab 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

Conditions

Head and Neck Carcinoma; Adenoid Cystic Carcinoma; Lung Cancer; Non-Small Cell Lung Cancer; Pancreatic Cancer; Mesothelioma; Esophageal Cancer; Any Solid Tumors Progressed After a Prior Immunotherapy; Head and Neck Squamous Cell Carcinoma; Head and Neck Squamous Cell Carcinoma HNSCC; Salivary Gland Carcinomas; Head and Neck Cancers - Salivary Gland; Head and Neck Cancers - Nasopharyngeal; Head and Neck Cancers - Throat; Small Cell Lung Cancer ( SCLC ); Lung Cancer (Locally Advanced or Metastatic); Head and Neck Cancers - Tonsils; Head and Neck Cancers Hypopharynx; Head and Neck Cancers Larynx; Head and Neck Cancers Lip; Head and Neck Cancers Nasopharynx; Head and Neck Cancers Oral Cavity; Head and Neck Cancers; Head and Neck Cancers Oropharynx; Head and Neck Cancers Trachea

Keywords

TrkA; NTRK1; Head and Neck Carcinoma; Adenoid Cystic Carcinoma; Lung Cancer; Non-Small Cell Lung Cancer; NSCLC; Mesothelioma; Pancreatic; Progression after anti PD-1/PD-L1 immunotherapy; Progressed after an immunotherapy; Esophageal; SCLC; ACC; HNSCC; Head and Neck Cancers; HNC; Salivary Gland Carcinoma; Nasopharyngeal; Throat; Tonsils; Hypopharynx; Larynx; Oral Cavity; Oropharynx; Trachea

Outcome Measures

Primary Outcomes (5)

• Number and severity of treatment-emergent Adverse Events (Phase 1)

  TEAE

  First cycle (21 days per cycle)

• To determine the recommended Phase 2 dose for VMD-928 (Phase 1)

  RP2D of monotherapy

  First cycle (21 days per cycle)

• To determine the RP2D of VMD-928 in combination with pembrolizumab (Phase 1)

  RP2D of combination therapy

  First cycle (21 days per cycle)

• Antitumor activity of VMD-928 in subjects with TrkA-driven tumors (Phase 2)

  Antitumor efficacy signal for monotherapy

  Up to 18 months

• Antitumor activity of VMD-928 in combination with pembrolizumab in subjects with TrkA-driven tumors (Phase 2)

  Antitumor efficacy signal for combination therapy

  Up to 18 months

Secondary Outcomes (4)

• Area under the plasma concentration versus time curve (AUC) of VMD-928.

  On Day 1 and Day 15 of Cycle 1 (each cycle is 21 days)

• Peak plasma concentration (Cmax) of VMD-928.

  On Day 1 and Day 15 of Cycle 1 (each cycle is 21 days)

• Incidence of Dose Limiting Toxicities.

  During the Cycle 1 (each cycle is 21 days)

• Correlation between clinical antitumor and TrkA protein expression.

  Up to the end of the Cycle 2 (each cycle is 21 days)

Study Arms (2)

VMD-928 monotherapy

EXPERIMENTAL

VMD-928 tablet monotherapy

Drug: VMD-928 100 mg Tablet

Combination Therapy

EXPERIMENTAL

VMD-928 tablet in combination with fixed dose of pembrolizumab 200 mg once-very-21-day (per cycle)

Drug: VMD-928 Tablet and Pembrolizumab (200 mg)

Interventions

VMD-928 100 mg Tablet DRUG

Taken orally once daily for 21 days per 21-day cycle

Also known as: Monotherapy

VMD-928 monotherapy

VMD-928 Tablet and Pembrolizumab (200 mg) DRUG

VMD-928 tablet (oral) starting at 300 mg daily for 21 days of 21-day cycle. Pemprolizumab at fixed intravenous dose of 200 mg once-every-21 days (per cycle) for max. 6 cycles.

Also known as: Combination therapy

Combination Therapy

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• #. Histologically or cytologically confirmed diagnosis of any type of solid tumor malignancy or lymphoma:
• Phase 1 Dose Escalation only: Subjects with
• (A) any advanced solid tumors of
• Head and Neck Cancers ("HNC") (of any types),
• Esophageal cancer,
• Lung cancers (of any types),
• Mesothelioma,
• Pancreatic cancers,
• Or,
• (B) any NTRK1 gene fusion positive ("NTRK1+") solid tumors or lymphomas, that is relapsed, refractory or intolerant (R/R/I) to standard of care (SOC) 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.
• Phase 2 Monotherapy and Combination with Pembrolizumab only:
• Subjects must have
• TrkA-driven HNC, Esophageal, Lung, Mesothelioma, Pancreatic cancers; or,
• any NTRK1+ solid tumors or lymphoma\*, that is R/R/I to SOC.
• Eastern Cooperative Oncology Group (ECOG) Performance Status: 0 or 1.

You may not qualify if:

• 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.
• Known active infections including HIV disease.
• 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.
• Patient has had or is currently having other malignant tumors within 3 years.
• Patients have multiple factors that affect their oral medication.
• Patients have long-term unhealed wounds or fractures.
• Patients have uncontrolled pleural effusion, pericardial effusion, or ascites that still require repeated drainage.

Sponsors & Collaborators

• VM Oncology, LLC: lead

Study Sites (15)

Providence Medical Foundation (site 209)

Santa Rosa, California, 95403, United States

RECRUITING

Hartford Hospital (site 210)

Hartford, Connecticut, 06102, United States

RECRUITING

The George Washington University Cancer Center (site 212)

Washington D.C., District of Columbia, 20037, United States

RECRUITING

Holy Cross Hospital (site 213)

Fort Lauderdale, Florida, 33308, United States

RECRUITING

Memorial Cancer Institute at Memorial Healthcare Systems (site 132)

Pembroke Pines, Florida, 33028, United States

RECRUITING

Englewood Hospital and Medical Center (site 202)

Englewood, New Jersey, 07631, United States

RECRUITING

Summit Medical Group (site 205)

Florham Park, New Jersey, 07932, United States

RECRUITING

Atlantic Health System, Morristown Medical Center (site 124)

Morristown, New Jersey, 07962, United States

RECRUITING

Presbyterian Kaseman Hospital (site 208)

Albuquerque, New Mexico, 87110, United States

RECRUITING

Weill Cornell Medicine, Cornell University (site 126)

New York, New York, 10065, United States

RECRUITING

Taylor Cancer Research Center (site 204)

Maumee, Ohio, 43537, United States

RECRUITING

Cancer Care Associates of York (site 206)

York, Pennsylvania, 17403, United States

RECRUITING

The University of Texas MD Anderson Cancer Center (site 127)

Houston, Texas, 77030, United States

RECRUITING

Utah Cancer Specialists (site 203)

Salt Lake City, Utah, 84106, United States

RECRUITING

PanOncology Trials, Hospital Oncologico - Puerto Rico Medical Center, Río Piedras (site 200)

San Juan, 00935, Puerto Rico

RECRUITING

MeSH Terms

Conditions

Carcinoma, Adenoid Cystic; Lung Neoplasms; Carcinoma, Non-Small-Cell Lung; Pancreatic Neoplasms; Mesothelioma; Esophageal Neoplasms; Squamous Cell Carcinoma of Head and Neck; Small Cell Lung Carcinoma; Neoplasm Metastasis; Head and Neck Neoplasms; Salivary Gland Neoplasms; Laryngeal Diseases; Tracheal Diseases

Interventions

Tablets; pembrolizumab; Combined Modality Therapy

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Lung Diseases; Respiratory Tract Diseases; Carcinoma, Bronchogenic; Bronchial Neoplasms; Digestive System Neoplasms; Endocrine Gland Neoplasms; Digestive System Diseases; Pancreatic Diseases; Endocrine System Diseases; Adenoma; Neoplasms, Mesothelial; Gastrointestinal Neoplasms; Esophageal Diseases; Gastrointestinal Diseases; Carcinoma, Squamous Cell; Neoplastic Processes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Mouth Neoplasms; Mouth Diseases; Stomatognathic Diseases; Salivary Gland Diseases; Otorhinolaryngologic Diseases

Intervention Hierarchy (Ancestors)

Dosage Forms; Pharmaceutical Preparations; Therapeutics

Study Officials

• Clinical Development

  VM Oncology

  STUDY CHAIR

Central Study Contacts

Jay Wu, PhD

CONTACT

1-510-270-2790; OM@VMOncology.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Tablet formulation and in Combination with Pembrolizumab: * Dose Escalation (Phase 1) * Cohort Expansion with RP2D (Phase 2)

Study Record Dates

• First Submitted: April 29, 2018
• First Posted: June 14, 2018
• Study Start: June 8, 2018
• Primary Completion (Estimated): December 1, 2027
• Study Completion (Estimated): June 1, 2028
• Last Updated: December 11, 2025

Record last verified: 2025-12

Locations

PR (1); US (14)