Head and Neck CarcinomaPhase 1/2NCT03556228
VMD-928 Monotherapy and in Combination With Pembrolizumab to Treat TrkA Overexpression Driven Solid Tumors or Lymphoma
A Phase 1/2 study testing VMD-928 100 mg Tablet and VMD-928 Tablet and Pembrolizumab (200 mg) in people with Head and Neck Carcinoma and Adenoid Cystic Carcinoma, run by VM Oncology, LLC at 15 sites in 2 countries.
Trial 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 Read more about this study
- Who is it for?
- Ages 18 to 80 years
- Conditions the study is for
- Head and Neck Carcinoma, Adenoid Cystic Carcinoma, Lung Cancer
- What is being tested?
- VMD-928 100 mg Tablet and VMD-928 Tablet and Pembrolizumab (200 mg)
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 242 participants
- Where
- 15 sitesin 2 countries
- Study dates
- 8 Jun 2018to Jun 2028
- Phase
- Phase 1/2
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- #. Histologically or cytologically confirmed diagnosis of any type of solid tumor malignancy or lymphoma:
- Phase 1 Dose Escalation only: Subjects with
- any advanced solid tumors of
- Head and Neck Cancers ("HNC") (of any types),
- Esophageal cancer,
- Lung cancers (of any types),
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- Mesothelioma,
- Pancreatic cancers,
- Or,
- 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.
- 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:
- Absolute neutrophil count ≥1.5x10^9/L
- Hemoglobin ≥9g/dL
- Platelets ≥100x10^9/L
- PT/INR, PTT ≤1.5xULN
- Total bilirubin ≤1.5x ULN
- AST, ALT ≤2.5xULN
- Creatinine ≤1.2xULN for age, weight
- Calculated creatinine clearance or 24h urine creatinine clearance ≥60mL/min
Who cannot join
- 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.
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- 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.
Trial locations and contacts
15 sites in 2 countries. Contact the study team or a site near you to ask about taking part.
15 sites in 2 countries
United States14 sites, 14 recruiting
- Recruiting
Presbyterian Kaseman Hospital (site 208)
Albuquerque, New Mexico, 87110
Matthew Widdows, CCRC, 505-559-6089, mwiddows2@phs.org
Monique Robertson, 505-559-6143, mrobertson2@phs.org
- Recruiting
Englewood Hospital and Medical Center (site 202)
Englewood, New Jersey, 07631
William Dippolito, 201-608-2572, William.Dippolito@EHMCHealth.org
Dara Herman, Dara.Herman@EHMCHealth.org
- Recruiting
Summit Medical Group (site 205)
Florham Park, New Jersey, 07932
Michelle Mackenzie, 973-436-1755, mmackenzie@summithealth.com
Romilda Moreira, 973-436-1748, rmoreira2@summithealth.com
- Recruiting
Holy Cross Hospital (site 213)
Fort Lauderdale, Florida, 33308
Eileen Georgi, 954-542-7748, eileen.georgi@holy-cross.com
Denise Pichardo, 954-542-8565, denise.pichardo@holy-cross.com
- Recruiting
Hartford Hospital (site 210)
Hartford, Connecticut, 06102
Hayley Yackel, 860-972-5518, hayley.dunnack@hhchealth.org
Christopher Sampson, 860-972-5026, christopher.sampson@hhchealth.org
- Recruiting
The University of Texas MD Anderson Cancer Center (site 127)
Houston, Texas, 77030
Madison Maas, MEMaas@mdanderson.org
Ly M Nguyen, 713-563-2169, LMNguyen1@mdanderson.org
- Recruiting
Taylor Cancer Research Center (site 204)
Maumee, Ohio, 43537
Stephanie Ambrose, RN, BSN, CCRC, 567.402.4502, sambrose@tcrcpt.org
Jessica Obarski, RN, CCRC, 567.402.4503, jobarski@tcrcpt.org
- Recruiting
Atlantic Health System, Morristown Medical Center (site 124)
Morristown, New Jersey, 07962
Salome Geene, 973-971-6373, salome.geene@atlantichealth.org
Tracey Hilden, RN, BSN, OCN, 973-971-7889, Tracey.Hilden@atlantichealth.org
- Recruiting
Weill Cornell Medicine, Cornell University (site 126)
New York, New York, 10065
Marvin Castellon, 646-962-6091, mac7087@med.cornell.edu
Jessica Wilk, jsw9043@med.cornell.edu
- Recruiting
Memorial Cancer Institute at Memorial Healthcare Systems (site 132)
Pembroke Pines, Florida, 33028
Shoria Martelly, 954-844-9917, SMartelly@mhs.net
Ines Padron Cubillan, 954-844-8737, IPadronCubillan@mhs.net
- Recruiting
Utah Cancer Specialists (site 203)
Salt Lake City, Utah, 84106
Angela Nuttall, 801-269-0231, anuttall@utahcancer.com
Angie Sonntag, 801-267-5605, asonntag@utahcancer.com; studies@utahcancer.com
- Recruiting
Providence Medical Foundation (site 209)
Santa Rosa, California, 95403
Melissa Ulrich, 707-521-3833, melissa.ulrich@providence.org
Sam Hansen, 707-521-3829, samantha.hansen@stjoe.org
- Recruiting
The George Washington University Cancer Center (site 212)
Washington D.C., District of Columbia, 20037
Emilie Ginovker, MS, BS, 202-994-2524, Emilie.ginovker@gwu.edu
Bethel Sebsebie, MS, BS, 202-994-1747, Bethel.sebsebie@gwu.edu
- Recruiting
Cancer Care Associates of York (site 206)
York, Pennsylvania, 17403
Katelyn Bean, kbean@cancercareyork.com
Jennifer Stough, 1-717-741-9229, jstough@cancercareyork.com
Puerto Rico1 site, 1 recruiting
- Recruiting
PanOncology Trials, Hospital Oncologico - Puerto Rico Medical Center, Río Piedras (site 200)
San Juan, 00935
Astrid K Martínez, (787) 407-3333, astrid.martinez@panoncologytrials.com
Carlos Quijano, (787) 607-3338, carlos.quijano@panoncologytrials.com
About this study
Official title: A Phase 1/2 Open-Label, Multiple-Dose, Dose-Escalation Study to Investigate the Safety, Pharmacokinetics, and Pharmacodynamics of VMD-928 as Monotherapy and in Combination With Pembrolizumab in Subjects With Solid Tumors or Lymphoma
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
Read the detailed description
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
- Head and Neck Carcinoma, Adenoid Cystic Carcinoma, Lung Cancer, Non-Small Cell Lung Cancer, Pancreatic Cancer, Mesothelioma
- Being tested
- VMD-928 100 mg Tablet, VMD-928 Tablet and Pembrolizumab (200 mg)
- 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
- Medical subject headings
- 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
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
VMD-928 100 mg TabletDrug
Also called Monotherapy
Taken orally once daily for 21 days per 21-day cycle
VMD-928 Tablet and Pembrolizumab (200 mg)Drug
Also called Combination therapy
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.
| Study group | Role | What they receive |
|---|---|---|
| VMD-928 monotherapy | Experimental | VMD-928 tablet monotherapy Receives: 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) Receives: Drug: VMD-928 Tablet and Pembrolizumab (200 mg) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number and severity of treatment-emergent Adverse Events (Phase 1)
TEAE
Measured: First cycle (21 days per cycle)
To determine the recommended Phase 2 dose for VMD-928 (Phase 1)
RP2D of monotherapy
Measured: First cycle (21 days per cycle)
To determine the RP2D of VMD-928 in combination with pembrolizumab (Phase 1)
RP2D of combination therapy
Measured: First cycle (21 days per cycle)
Antitumor activity of VMD-928 in subjects with TrkA-driven tumors (Phase 2)
Antitumor efficacy signal for monotherapy
Measured: 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
Measured: Up to 18 months
Secondary outcomes (4)
Area under the plasma concentration versus time curve (AUC) of VMD-928.
AUC
Measured: On Day 1 and Day 15 of Cycle 1 (each cycle is 21 days)
Peak plasma concentration (Cmax) of VMD-928.
Cmax
Measured: On Day 1 and Day 15 of Cycle 1 (each cycle is 21 days)
Incidence of Dose Limiting Toxicities.
# of DLTs
Measured: During the Cycle 1 (each cycle is 21 days)
Correlation between clinical antitumor and TrkA protein expression.
Relationship of TrkA vs. efficacy
Measured: Up to the end of the Cycle 2 (each cycle is 21 days)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Jun 2018
- Study start8 Jun 2018
- Primary completionDec 2027 (estimated)
- Study completionJun 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Head and Neck CarcinomaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Model description
- Tablet formulation and in Combination with Pembrolizumab: * Dose Escalation (Phase 1) * Cohort Expansion with RP2D (Phase 2)
- Masking
- None (open label)
- Enrolment
- 242 participants (estimated)
Sponsor and investigators
- Lead sponsor
- VM Oncology, LLC
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Clinical Development, Study chair, VM Oncology
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03556228
- Sponsor's protocol ID
- VMO-01C
- Status last verified
- Dec 2025
- First submitted
- 29 Apr 2018
- Last updated
- 11 Dec 2025
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Undecided