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

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ClinicalTrials.gov Identifier: NCT03556228
Recruitment Status : Recruiting
First Posted : June 14, 2018
Last Update Posted : March 15, 2021
Sponsor:
Information provided by (Responsible Party):
VM Oncology, LLC

Tracking Information
First Submitted Date  ICMJE April 29, 2018
First Posted Date  ICMJE June 14, 2018
Last Update Posted Date March 15, 2021
Actual Study Start Date  ICMJE June 8, 2018
Estimated Primary Completion Date June 2022   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: June 1, 2018)
Number and severity of treatment-emergent AEs [ Time Frame: Within two months of the first VMD-928 dose for each patient ]
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: June 13, 2018)
  • 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] ]
  • Peak plasma concentration (Cmax) of VMD-928. [ Time Frame: Two to three months after starting treatment for each patient [Estimated] ]
  • Incidence of Dose Limiting Toxicities. [ Time Frame: Within two months of the first VMD-928 dose for each patient ]
  • Analgesic response as defined by the Brief Pain Inventory (BPI). [ Time Frame: Within two months after starting treatment for each patient [Estimated] ]
  • Change in p-TrkA protein expression. [ Time Frame: Pre-dose and within two months after starting treatment for each patient [Estimated] ]
  • Correlation between clinical antitumor and AUC. [ Time Frame: Six to eight months after starting treatment for each patient [Estimated] ]
  • Correlation between clinical antitumor and p-TrkA inhibition. [ Time Frame: Six to eight months after starting treatment for each patient [Estimated] ]
  • Correlation between analgesic response and p-TrkA inhibition. [ Time Frame: Six to eight months after starting treatment for each patient [Estimated] ]
  • Correlation between analgesic response and AUC. [ Time Frame: Six to eight months after starting treatment for each patient [Estimated] ]
Original Secondary Outcome Measures  ICMJE
 (submitted: June 1, 2018)
  • 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] ]
  • Peak plasma concentration (Cmax) of VMD-928. [ Time Frame: Two to three months after starting treatment for each patient [Estimated] ]
  • Incidence of Dose Limiting Toxicities. [ Time Frame: Within two months of the first VMD-928 dose for each patient ]
  • Analgesic response as defined by the Brief Pain Inventory (BPI). [ Time Frame: Within two months after starting treatment for each patient [Estimated] ]
  • Change in p-TrkA protein expression. [ Time Frame: Within two months after starting treatment for each patient [Estimated] ]
  • Correlation between clinical antitumor and AUC. [ Time Frame: Six to eight months after starting treatment for each patient [Estimated] ]
  • Correlation between clinical antitumor and p-TrkA inhibition. [ Time Frame: Six to eight months after starting treatment for each patient [Estimated] ]
  • Correlation between analgesic response and p-TrkA inhibition. [ Time Frame: Six to eight months after starting treatment for each patient [Estimated] ]
  • Correlation between analgesic response and AUC. [ Time Frame: Six to eight months after starting treatment for each patient [Estimated] ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Oral TrkA Inhibitor VMD-928 for Treatment of Advanced Adult Solid Tumors or Lymphoma
Official Title  ICMJE 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
Brief Summary 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.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: N/A
Intervention Model: Sequential Assignment
Intervention Model Description:
  • Part 1, Dose Escalation: Identify the RP2D (complete);
  • Parts 2-4, Cohort Expansion with RP2D (ongoing);
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • 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
Intervention  ICMJE Drug: VMD-928 300 mg Tablets or 100 mg Capsules
Taken orally once daily
Study Arms  ICMJE Experimental: VMD-928 300 mg Tablet or 100 mg Capsule
Intervention: Drug: VMD-928 300 mg Tablets or 100 mg Capsules
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: June 1, 2018)
54
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE December 2022
Estimated Primary Completion Date June 2022   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Jay Wu, PhD 510-661-6770 ext 101 OM@VMOncology.com
Contact: Liz Gaynor; Cameron Wright 602-358-8344; 602-358-8341 egaynor@td2inc.com; cwright@td2inc.com
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03556228
Other Study ID Numbers  ICMJE VMO-01C
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: Undecided
Responsible Party VM Oncology, LLC
Study Sponsor  ICMJE VM Oncology, LLC
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Peg Fletcher, MD PhD MedAssessment
PRS Account VM Oncology, LLC
Verification Date March 2021

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP