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Selektiv TrkA-hæmmer VMD-928 til behandling af TrkA-overekspressionsdrevne solide tumorer eller lymfom

30. oktober 2026 opdateret af: VM Oncology, LLC

En åben-label, multiple-dosis, dosis-eskaleringsundersøgelse for at undersøge sikkerheden, farmakokinetikken og farmakodynamikken af ​​VMD-928 hos forsøgspersoner med solide tumorer eller lymfom

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

Studieoversigt

Status

Rekruttering

Betingelser

Intervention / Behandling

Detaljeret beskrivelse

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.

Undersøgelsestype

Interventionel

Tilmelding (Anslået)

242

Fase

  • Fase 2
  • Fase 1

Kontakter og lokationer

Dette afsnit indeholder kontaktoplysninger for dem, der udfører undersøgelsen, og oplysninger om, hvor denne undersøgelse udføres.

Studiekontakt

Studiesteder

  • Forenede Stater
    • California
      • Santa Rosa, California, Forenede Stater, 95403
    • Connecticut
      • Hartford, Connecticut, Forenede Stater, 06102
    • District of Columbia
      • Washington D.C., District of Columbia, Forenede Stater, 20037
        • Rekruttering
        • The George Washington University Cancer Center (site 212)
        • Kontakt:
        • Ledende efterforsker:
          • Pavani Chalasani, MD, MPH
        • Kontakt:
    • Florida
      • Fort Lauderdale, Florida, Forenede Stater, 33308
      • Pembroke Pines, Florida, Forenede Stater, 33028
        • Rekruttering
        • Memorial Cancer Institute at Memorial Healthcare Systems (site 132)
        • Ledende efterforsker:
          • Luis E Raez, MD
        • Kontakt:
        • Kontakt:
    • New Jersey
      • Englewood, New Jersey, Forenede Stater, 07631
      • Florham Park, New Jersey, Forenede Stater, 07932
        • Rekruttering
        • Summit Medical Group (site 205)
        • Kontakt:
        • Ledende efterforsker:
          • Steven Papish, MD, FACP
      • Morristown, New Jersey, Forenede Stater, 07962
        • Rekruttering
        • Atlantic Health System, Morristown Medical Center (site 124)
        • Ledende efterforsker:
          • Angela Alistar, MD
        • Kontakt:
        • Kontakt:
    • New Mexico
      • Albuquerque, New Mexico, Forenede Stater, 87110
        • Rekruttering
        • Presbyterian Kaseman Hospital (site 208)
        • Kontakt:
        • Ledende efterforsker:
          • Ethan Binder, MD
        • Kontakt:
    • New York
      • New York, New York, Forenede Stater, 10065
        • Rekruttering
        • Weill Cornell Medicine, Cornell University (site 126)
        • Kontakt:
        • Kontakt:
        • Ledende efterforsker:
          • Ashish Saxena, M.D., Ph.D.
    • Pennsylvania
      • York, Pennsylvania, Forenede Stater, 17403
        • Rekruttering
        • Cancer Care Associates of York (site 206)
        • Ledende efterforsker:
          • Chanh Huynh, MD
        • Kontakt:
        • Kontakt:
    • Texas
      • Houston, Texas, Forenede Stater, 77030
        • Rekruttering
        • The University of Texas MD Anderson Cancer Center (site 127)
        • Ledende efterforsker:
          • David S Hong, MD
        • Kontakt:
        • Kontakt:
  • Puerto Rico
      • San Juan, Puerto Rico, 00935

Deltagelseskriterier

Forskere leder efter personer, der passer til en bestemt beskrivelse, kaldet berettigelseskriterier. Nogle eksempler på disse kriterier er en persons generelle helbredstilstand eller tidligere behandlinger.

Berettigelseskriterier

Aldre berettiget til at studere

18 år til 80 år (Voksen, Ældre voksen)

Tager imod sunde frivillige

Ingen

Køn, der er berettiget til at studere

Alle

Beskrivelse

Key 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.

Key Inclusion Criteria:

  • 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

Key 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.

Studieplan

Dette afsnit indeholder detaljer om studieplanen, herunder hvordan undersøgelsen er designet, og hvad undersøgelsen måler.

Hvordan er undersøgelsen tilrettelagt?

Design detaljer

  • Primært formål: Behandling
  • Tildeling: Ikke-randomiseret
  • Interventionel model: Sekventiel tildeling
  • Maskning: Ingen (Åben etiket)

Våben og indgreb

Deltagergruppe / Arm
Intervention / Behandling
Eksperimentel: VMD-928 monotherapy

VMD-928 tablet monotherapy
Medicin: VMD-928 100 mg Tablet

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

Andre navne:
  • Monoterapi
Eksperimentel: Combination Therapy

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

Andre navne:
  • Kombinationsterapi

Hvad måler undersøgelsen?

Primære resultatmål

Resultatmål
Foranstaltningsbeskrivelse
Tidsramme
Number and severity of treatment-emergent Adverse Events (Phase 1)
Tidsramme: First cycle (21 days per cycle)

TEAE
First cycle (21 days per cycle)
To determine the recommended Phase 2 dose for VMD-928 (Phase 1)
Tidsramme: First cycle (21 days per cycle)

RP2D of monotherapy
First cycle (21 days per cycle)
To determine the RP2D of VMD-928 in combination with pembrolizumab (Phase 1)
Tidsramme: First cycle (21 days per cycle)

RP2D of combination therapy
First cycle (21 days per cycle)
Antitumor activity of VMD-928 in subjects with TrkA-driven tumors (Phase 2)
Tidsramme: Up to 18 months

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)
Tidsramme: Up to 18 months

Antitumor efficacy signal for combination therapy
Up to 18 months

Sekundære resultatmål

Resultatmål
Foranstaltningsbeskrivelse
Tidsramme
Area under the plasma concentration versus time curve (AUC) of VMD-928.
Tidsramme: On Day 1 and Day 15 of Cycle 1 (each cycle is 21 days)

AUC
On Day 1 and Day 15 of Cycle 1 (each cycle is 21 days)
Peak plasma concentration (Cmax) of VMD-928.
Tidsramme: On Day 1 and Day 15 of Cycle 1 (each cycle is 21 days)

Cmax
On Day 1 and Day 15 of Cycle 1 (each cycle is 21 days)
Incidence of Dose Limiting Toxicities.
Tidsramme: During the Cycle 1 (each cycle is 21 days)

# of DLTs
During the Cycle 1 (each cycle is 21 days)
Correlation between clinical antitumor and TrkA protein expression.
Tidsramme: Up to the end of the Cycle 2 (each cycle is 21 days)

Relationship of TrkA vs. efficacy
Up to the end of the Cycle 2 (each cycle is 21 days)

Samarbejdspartnere og efterforskere

Det er her, du vil finde personer og organisationer, der er involveret i denne undersøgelse.

Sponsor

VM Oncology, LLC

Efterforskere

  • Studiestol: Clinical Development, VM Oncology

Datoer for undersøgelser

Disse datoer sporer fremskridtene for indsendelser af undersøgelsesrekord og resumeresultater til ClinicalTrials.gov. Studieregistreringer og rapporterede resultater gennemgås af National Library of Medicine (NLM) for at sikre, at de opfylder specifikke kvalitetskontrolstandarder, før de offentliggøres på den offentlige hjemmeside.

Studer store datoer

Studiestart (Faktiske)

8. juni 2018

Primær færdiggørelse (Anslået)

1. december 2027

Studieafslutning (Anslået)

1. juni 2028

Datoer for studieregistrering

Først indsendt

29. april 2018

Først indsendt, der opfyldte QC-kriterier

1. juni 2018

Først opslået (Faktiske)

14. juni 2018

Opdateringer af undersøgelsesjournaler

Sidste opdatering sendt (Faktiske)

4. november 2026

Sidste opdatering indsendt, der opfyldte kvalitetskontrolkriterier

30. oktober 2026

Sidst verificeret

1. oktober 2026

Mere information

Begreber relateret til denne undersøgelse

Nøgleord

Yderligere relevante MeSH-vilkår

Andre undersøgelses-id-numre

  • VMO-01C

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Ingen

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