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

See Contacts and Locations

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

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

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

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

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):

Received chemotherapy having delayed toxicity within the last 21 days (six weeks for prior nitrosourea or mitomycin C).
Received anticancer therapy with radiation, immunotherapy, a biologic, surgery and/or tumor embolization within the past 2 weeks.
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.
Unresolved toxicity from previous anti-cancer therapy ≥ CTCAE Grade 1 (except alopecia or anemia) unless agreed to by both the Investigator and Sponsor.
Negative result on TrkA-specific or pan-Trk IHC assay (Parts 2-4 only).
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 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):
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

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

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