Ph1 Administration of VSV-IFNβ-NIS Monotherapy and in Combination With Avelumab in Pts With Refractory Solid Tumors

April 25, 2022 updated by: Vyriad, Inc.

Phase 1 Trial of Vesicular Stomatitis Virus Genetically Engineered to Express NIS and Human Interferon Beta (VSV-IFNβ-NIS) Monotherapy and in Combination With Avelumab, in Patients With Refractory Solid Tumors

This is a three-part open label phase 1 study designed to determine the safety profile, MTD, PK and tumor and biomarker response after IT or IV administration of a single dose of VSV-IFNβ-NIS, or combined IT followed by IV VSV-IFNβ-NIS, with or without IV avelumab every two weeks, in patients with refractory advanced/metastatic solid tumors.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

The study consists of three parts: a single ascending dose escalation of IT VSV-IFNβ-NIS monotherapy, a monotherapy IV regimen selection phase and an expansion phase, designed to explore the safety and efficacy of the chosen monotherapy regimen alone or in combination with avelumab in patients with metastatic colorectal cancer. Monotherapy will also be explored in patients with pheochromocytoma and NET.

Patients are required to have at least 1 measurable lesion per RECIST 1.1, and in the IT-containing arms this lesion should be amenable for a one-time IT injection of VSV-IFNβ-NIS. At least one patient per IT cohort is required to have at least 2 measurable lesions per RECIST 1.1, one for a one-time IT injection of VSV-IFNβ-NIS and one to be used as a control. Priority enrollment in the IT-containing arms will be granted to patients with 2 measurable lesions per RECIST 1.1. At least one patient per dose level should have metastatic colorectal cancer. In order to fulfil these requirements, at least 3 or 4 patients will be required per escalation dose cohort. Other tumor types of particular interest based on prior experience with VSV or oncolytic viruses include malignant melanoma and endometrial cancer. When more than one cohort is open simultaneously, slot assignment will be determined by the sponsor in consultation with the PIs.

Study Type

Interventional

Enrollment (Actual)

76

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Florida
      • Miami, Florida, United States, 33136
        • University of Miami
    • Minnesota
      • Minneapolis, Minnesota, United States, 55455
        • Masonic Cancer Center, University of Minnesota
    • Ohio
      • Columbus, Ohio, United States, 43205/2664
        • Nationwide Children's Hospital
    • South Dakota
      • Sioux Falls, South Dakota, United States, 57104
        • Sanford Cancer Center
    • Tennessee
      • Nashville, Tennessee, United States, 37203
        • Sarah Cannon Research Institute
    • Texas
      • Dallas, Texas, United States, 75230
        • Mary Crowley Cancer Research Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

14 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Be > 18 years of age on day of signing informed consent.
  • Have a histologically confirmed diagnosis of an advanced and/or metastatic solid tumor that is relapsed and/or refractory to standard therapy, as defined as progression on at least one prior line of therapy in the relapsed/metastatic setting and no existing options are felt to provide clinical benefit.
  • Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) 0 or 1.
  • Adequate hematological, liver and kidney function.
  • Must be willing to implement contraception throughout study and for 120 days after receiving the study drug.

Exclusion Criteria:

  • Has been receiving: radiotherapy, chemotherapy, or molecularly-targeted agents or tyrosine kinase inhibitors within 2 weeks or 5 half-lives (whichever is longer) of the start of study treatment; immunotherapy/monoclonal antibodies within 3 weeks of the start of study treatment; nitrosoureas, antibody-drug conjugates, or radioactive isotopes within 6 weeks of the start of study treatment.
  • Has a history of a bone marrow or solid organ transplant.
  • Is pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the trial, starting with the pre-screening or screening visit through 120 days after the last dose of trial treatment.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: VSV-IFNβ-NIS
VSV-IFNβ-NIS will be administered intratumorally as a single dose on day 1.
Biological: VSV-IFNβ-NIS
Intratumoral injection of a single dose of VSV-IFNβ-NIS
Experimental: Selection of VSV-IFNβ-NIS Monotherapy
VSV-IFNβ-NIS will be administered either intratumorally, intravenously or with a combination of intratumorally and intravenously as a single dose on day 1.
Biological: VSV-IFNβ-NIS
Intratumoral injection of a single dose of VSV-IFNβ-NIS
Experimental: VSV-IFNβ-NIS and avelumab

VSV-IFNβ-NIS will be administered as determined in arm 2 as a single dose on day 1.

Avelumab will be administered intravenously every 2 weeks starting on day 1.
Biological: VSV-IFNβ-NIS and avelumab
Intratumoral injection of a single dose of VSV-IFNβ-NIS and intravenous infusion of avelumab

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Maximum Tolerated Dose (MTD) of VSV-IFNβ-NIS Monotherapy and Combination Therapy
Time Frame: 21 days after VSV-IFNβ-NIS Monotherapy or Combination Therapy for each dose cohort
21 days after VSV-IFNβ-NIS Monotherapy or Combination Therapy for each dose cohort

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Vyriad, Inc.

Investigators

  • Principal Investigator: Alice Bexon, MD, CMO

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

April 17, 2017

Primary Completion (Actual)

February 5, 2022

Study Completion (Actual)

April 22, 2022

Study Registration Dates

First Submitted

September 30, 2016

First Submitted That Met QC Criteria

October 3, 2016

First Posted (Estimate)

October 4, 2016

Study Record Updates

Last Update Posted (Actual)

April 27, 2022

Last Update Submitted That Met QC Criteria

April 25, 2022

Last Verified

April 1, 2022

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • VYR-VSV2-101

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

No

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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