Clinical Trials /

Oral TrkA Inhibitor VMD-928 for Treatment of Advanced Adult Solid Tumors or Lymphoma

NCT03556228

Description:

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

Related Conditions:
  • Acute Myeloid Leukemia
  • Adenoid Cystic Carcinoma
  • Breast Carcinoma
  • Cervical Carcinoma
  • Esophagogastric Carcinoma
  • Head and Neck Squamous Cell Carcinoma
  • Hematopoietic and Lymphoid Malignancy
  • Hepatocellular Carcinoma
  • Lymphoma
  • Malignant Solid Tumor
  • Melanoma
  • Mesothelioma
  • Non-Hodgkin Lymphoma
  • Ovarian Carcinoma
  • Pancreatic Carcinoma
  • Prostate Carcinoma
  • Squamous Cell Lung Carcinoma
  • Thymic Carcinoma
  • Thymoma
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: Oral TrkA Inhibitor VMD-928 for Treatment of Advanced Adult Solid Tumors or Lymphoma
  • 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 IDs

  • ORG STUDY ID: VMO-01C
  • NCT ID: NCT03556228

Conditions

  • Thymic Carcinoma and Thymoma
  • Mesothelioma
  • Head and Neck Squamous Cell Carcinoma
  • Ovarian Cancer
  • Hepatocellular Carcinoma
  • Squamous Cell Carcinoma of Lung
  • Esophageal Cancer
  • Adenoid Cystic Carcinoma
  • Prostate Cancer
  • Cervical Cancer
  • Gastric Cancer
  • Melanoma
  • Acute Myeloid Leukemia
  • Non Hodgkin Lymphoma

Interventions

DrugSynonymsArms
VMD-928 300 mg Tablets or 100 mg CapsulesVMD-928 300 mg Tablet or 100 mg Capsule

Purpose

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

Detailed 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.
    

Trial Arms

NameTypeDescriptionInterventions
VMD-928 300 mg Tablet or 100 mg CapsuleExperimental
  • VMD-928 300 mg Tablets or 100 mg Capsules

Eligibility Criteria

        Part-1 Dose Escalation [Key Inclusion]:

          -  Histologically or cytologically confirmed diagnosis of solid tumor malignancy or
             lymphoma that is not responsive to standard therapies, are unfit for standard
             chemotherapy or for which there is no approved or curative therapy.

          -  ECOG score of 0 or 1.

          -  Able to swallow and retain oral medication.

          -  Adequate organ system function.

        Parts 2-4 Cohort Expansion Only [Key Inclusion]:

          -  Part 1 inclusion criteria.

          -  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, AND have a tumor or tumor type in one of the following categories:

             (i). Tumors showing a response or stable disease after at least 2 cycles of VMD-928
             during Part 1;

        (ii). Tumor types associated with high TrkA protein overexpression, i.e.:

          -  Thymic carcinoma and thymoma

          -  Mesothelioma

          -  Head and neck squamous cell carcinoma (HNSCC)

          -  Ovarian cancer (especially serous)

          -  Hepatocellular carcinoma

          -  Squamous cell carcinoma of lung (squamous NSCLC)

          -  Esophageal cancer

          -  Adenoid cystic carcinoma

          -  Prostate cancer

          -  Cervical cancer

          -  Gastric cancer

          -  Melanoma

          -  Acute myeloid leukemia

          -  Pancreatic carcinoma

          -  Non-Hodgkins' lymphoma

        (iii). Tumors with documented NTRK1 gene fusions or amplifications, or TrkA protein
        overexpression, or a tumor which has progressed due to NTRK1 mutation after treatment of a
        pan-Trk inhibitor (e.g. larotrectinib or entrectinib)

        Part 3 Pharmacodynamic Activity only (Eligible subjects in Part 2 may enroll in Part 3):

          -  Part-2 inclusion criteria.

          -  Tumor with readily accessible lesion that is amenable to biopsy and consent to pre-and
             post-dose biopsy.

        Part 4 Exploratory Comparative PK of Tablet vs. Capsule Formulations only (Eligible
        subjects in Part 2 or 3 will be encouraged to enroll in Part 4)

        Key Exclusion Criteria (Parts 1-4):

          1. Received chemotherapy having delayed toxicity within the last 21 days (six weeks for
             prior nitrosourea or mitomycin C).

          2. Received anticancer therapy with radiation, immunotherapy, a biologic, surgery and/or
             tumor embolization within the past 2 weeks.

          3. Received an investigational anti-cancer drug within 21 days or 5 half-lives of the
             investigational agent prior, whichever is longer, to the first dose of VMD-928.

          4. Unresolved toxicity from previous anti-cancer therapy ≥ CTCAE Grade 1 (except alopecia
             or anemia) unless agreed to by both the Investigator and Sponsor.

          5. Negative result on TrkA-specific or pan-Trk IHC assay (Parts 2-4 only).

          6. Known active infections including HIV disease.

          7. Currently pregnant, nursing, or planning to become pregnant during the course of the
             study.

          8. QTcF interval ≥ 480 msec.

          9. Class II, III, or IV heart failure as defined by the New York Heart Association (NYHA)
             functional classification system.

         10. Acute coronary syndromes (including unstable angina), coronary angioplasty, or
             stenting within the past 24 weeks.

         11. Unstable or uncompensated respiratory, hepatic, renal, or cardiac disease that would
             compromise the patient's safety or interfere with assessment of the drug.

         12. Psychological, familial, sociological, geographical or other concurrent conditions
             that would interfere with safety evaluation, limit the subject's ability to follow the
             procedures in the protocol or otherwise jeopardize compliance with the protocol.
             Subjects with uncontrolled major depression, bipolar disorder, or severe anxiety
             disorder are excluded.

             Key Exclusion Criteria (For Parts 1 and 4 only):

         13. Any current medical condition that would alter the absorption, distribution,
             metabolism or excretion of VMD-928 including but not limited to:

               -  Severe uncontrolled nausea or vomiting

               -  Severe uncontrolled diarrhea

               -  With a history of short bowel syndrome

               -  Clinically diagnosed malabsorption secondary to bowel resection
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Number and severity of treatment-emergent AEs
Time Frame:Within two months of the first VMD-928 dose for each patient
Safety Issue:
Description:

Secondary Outcome Measures

Measure:Area under the plasma concentration versus time curve (AUC) of VMD-928.
Time Frame:Two to three months after starting treatment for each patient [Estimated]
Safety Issue:
Description:
Measure:Peak plasma concentration (Cmax) of VMD-928.
Time Frame:Two to three months after starting treatment for each patient [Estimated]
Safety Issue:
Description:
Measure:Incidence of Dose Limiting Toxicities.
Time Frame:Within two months of the first VMD-928 dose for each patient
Safety Issue:
Description:
Measure:Analgesic response as defined by the Brief Pain Inventory (BPI).
Time Frame:Within two months after starting treatment for each patient [Estimated]
Safety Issue:
Description:
Measure:Change in p-TrkA protein expression.
Time Frame:Pre-dose and within two months after starting treatment for each patient [Estimated]
Safety Issue:
Description:
Measure:Correlation between clinical antitumor and AUC.
Time Frame:Six to eight months after starting treatment for each patient [Estimated]
Safety Issue:
Description:
Measure:Correlation between clinical antitumor and p-TrkA inhibition.
Time Frame:Six to eight months after starting treatment for each patient [Estimated]
Safety Issue:
Description:
Measure:Correlation between analgesic response and p-TrkA inhibition.
Time Frame:Six to eight months after starting treatment for each patient [Estimated]
Safety Issue:
Description:
Measure:Correlation between analgesic response and AUC.
Time Frame:Six to eight months after starting treatment for each patient [Estimated]
Safety Issue:
Description:

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:VM Oncology, LLC

Trial Keywords

  • TrkA
  • NTRK1
  • Thymic carcinoma and thymoma
  • Mesothelioma
  • Head and Neck Squamous Cell Carcinoma
  • Ovarian Cancer
  • Hepatocellular Carcinoma
  • Squamous Cell Carcinoma of Lung (squamous NSCLC)
  • Esophageal Cancer
  • Adenoid Cystic Carcinoma
  • Prostate Cancer
  • Cervical Cancer
  • Gastric Cancer
  • Melanoma
  • Acute Myeloid Leukemia
  • Non Hodgkin Lymphoma

Last Updated

December 8, 2020