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

NCT ID: NCT03556228

Last Updated: 2025-12-11

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

PHASE1/PHASE2

Total Enrollment

242 participants

Study Classification

INTERVENTIONAL

Study Start Date

2018-06-08

Study Completion Date

2028-06-30

Brief Summary

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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

Detailed Description

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This is an open-label, dose-escalation (Phase 1) and expansion (Phase 2) multi-center study conducted in five parts to identify the safe and pharmacologically active doses (MTD and/orRP2D) and regimen for oral VMD-928 monotherapy and in combination with a PD-1 inhibitor, pembrolizumab in cancer patients. An immunohistochemistry (IHC) assay specific for detecting TrkA protein in tumor tissue samples has been validated and is being used to detect TrkA protein expressions in patient tumor tissue samples at Pre-screening. The study is currently focusing on the top 5 solid tumor with the highest TrkA protein overexpression are: Head and Neck Cancers (HNC), Esophageal cancer, Lung cancers, Mesothelioma, and Pancreatic Cancer.

Conditions

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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

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

SEQUENTIAL

Tablet formulation and in Combination with Pembrolizumab:

* Dose Escalation (Phase 1)
* Cohort Expansion with RP2D (Phase 2)
Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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VMD-928 monotherapy

VMD-928 tablet monotherapy

Group Type EXPERIMENTAL

VMD-928 100 mg Tablet

Intervention Type DRUG

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

Combination Therapy

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

Group Type EXPERIMENTAL

VMD-928 Tablet and Pembrolizumab (200 mg)

Intervention Type 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.

Interventions

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VMD-928 100 mg Tablet

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

Intervention Type DRUG

VMD-928 Tablet and Pembrolizumab (200 mg)

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.

Intervention Type DRUG

Other Intervention Names

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Monotherapy Combination therapy

Eligibility Criteria

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Inclusion Criteria

#. 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

1. Head and Neck Cancers ("HNC") (of any types),
2. Esophageal cancer,
3. Lung cancers (of any types),
4. Mesothelioma,
5. 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

1. TrkA-driven HNC, Esophageal, Lung, Mesothelioma, Pancreatic cancers; or,
2. any NTRK1+ solid tumors or lymphoma\*, that is R/R/I to SOC.


* Eastern Cooperative Oncology Group (ECOG) Performance Status: 0 or 1.
* Able to swallow and retain oral medication.
* Subjects must either have available archival tumor tissue samples, or consent to tumor tissue sampling prior to the first dose.
* 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

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.
* 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.
* Patients are taking the following drugs and can't stop them during the study:

* Tylenol or medicine containing acetaminophen (paracetamol).
* Antacids (e.g. TUMS, calcium carbonate, or magnesium hydroxide), proton pump inhibitors (e.g. omeprazole), H2 blockers (e.g. famotidine), or buffered vitamins.
* Epstein-Barr virus (EBV) negative nasopharyngeal carcinoma.

For Phase 2 only:

* Negative result on TrkA immunohistochemistry (IHC) assay.
* Have visceral crisis, defined as severe organ dysfunction and rapid progression of the cancer. (It is not about presence of visceral metastasis.)

For combination therapy with Pembrolizumab only:

* Serious adverse immune related adverse events (grade 3 or 4) with previous PD-1(L1) inhibitor therapy, that were symptomatic and required prolong immunosuppression (\>6 weeks).
* Any grade Pneumonitis and Myocarditis related to prior PD-1(L1) inhibitor therapy.
* For subjects that received PD-1(L1) inhibitors before, there should be a washout period of at least 21 days between the last day of PD-1(L1) inhibitor and first day of study medications.
* Subjects who relapsed after prior treatment with PD-1(L1) inhibitors. Relapsed is defined as patients having best overall response of CR or PR after treatment with a PD-1(L1) inhibitor.
Minimum Eligible Age

18 Years

Maximum Eligible Age

80 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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VM Oncology, LLC

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Clinical Development

Role: STUDY_CHAIR

VM Oncology

Locations

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Providence Medical Foundation (site 209)

Santa Rosa, California, United States

Site Status RECRUITING

Hartford Hospital (site 210)

Hartford, Connecticut, United States

Site Status RECRUITING

The George Washington University Cancer Center (site 212)

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

Site Status RECRUITING

Holy Cross Hospital (site 213)

Fort Lauderdale, Florida, United States

Site Status RECRUITING

Memorial Cancer Institute at Memorial Healthcare Systems (site 132)

Pembroke Pines, Florida, United States

Site Status RECRUITING

Englewood Hospital and Medical Center (site 202)

Englewood, New Jersey, United States

Site Status RECRUITING

Summit Medical Group (site 205)

Florham Park, New Jersey, United States

Site Status RECRUITING

Atlantic Health System, Morristown Medical Center (site 124)

Morristown, New Jersey, United States

Site Status RECRUITING

Presbyterian Kaseman Hospital (site 208)

Albuquerque, New Mexico, United States

Site Status RECRUITING

Weill Cornell Medicine, Cornell University (site 126)

New York, New York, United States

Site Status RECRUITING

Taylor Cancer Research Center (site 204)

Maumee, Ohio, United States

Site Status RECRUITING

Cancer Care Associates of York (site 206)

York, Pennsylvania, United States

Site Status RECRUITING

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

Houston, Texas, United States

Site Status RECRUITING

Utah Cancer Specialists (site 203)

Salt Lake City, Utah, United States

Site Status RECRUITING

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

San Juan, , Puerto Rico

Site Status RECRUITING

Countries

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United States Puerto Rico

Central Contacts

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Jay Wu, PhD

Role: CONTACT

1-510-270-2790 ext. 101

Facility Contacts

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Melissa Ulrich

Role: primary

707-521-3833

Sam Hansen

Role: backup

707-521-3829

Hayley Yackel

Role: primary

860-972-5518

Christopher Sampson

Role: backup

860-972-5026

Emilie Ginovker, MS, BS

Role: primary

202-994-2524

Bethel Sebsebie, MS, BS

Role: backup

202-994-1747

Eileen Georgi

Role: primary

954-542-7748

Denise Pichardo

Role: backup

954-542-8565

Shoria Martelly

Role: primary

954-844-9917

Ines Padron Cubillan

Role: backup

954-844-8737

William Dippolito

Role: primary

201-608-2572

Dara Herman

Role: backup

Michelle Mackenzie

Role: primary

973-436-1755

Romilda Moreira

Role: backup

973-436-1748

Salome Geene

Role: primary

973-971-6373

Tracey Hilden, RN, BSN, OCN

Role: backup

973-971-7889

Matthew Widdows, CCRC

Role: primary

505-559-6089

Monique Robertson

Role: backup

505-559-6143

Marvin Castellon

Role: primary

646-962-6091

Jessica Wilk

Role: backup

Stephanie Ambrose, RN, BSN, CCRC

Role: primary

567.402.4502

Jessica Obarski, RN, CCRC

Role: backup

567.402.4503

Katelyn Bean

Role: primary

Jennifer Stough

Role: backup

1-717-741-9229

Madison Maas

Role: primary

Ly M Nguyen

Role: backup

713-563-2169

Angela Nuttall

Role: primary

801-269-0231

Angie Sonntag

Role: backup

Astrid K Martínez

Role: primary

(787) 407-3333

Carlos Quijano

Role: backup

(787) 607-3338

Other Identifiers

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VMO-01C

Identifier Type: -

Identifier Source: org_study_id

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