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

Malignant Solid Tumour Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02923466
• Other study ID #: VYR-VSV2-101
• Status: Completed
• Phase: Phase 1
• Start date: April 17, 2017
• Est. completion date: April 22, 2022

Study information

• Verified date: April 2022
• Source: Vyriad, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 76
• Est. completion date: April 22, 2022
• Est. primary completion date: February 5, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Malignant Solid Tumour
• Neoplasms

Intervention

Biological:
• VSV-IFNß-NIS
Intratumoral injection of a single dose of VSV-IFNß-NIS
• VSV-IFNß-NIS and avelumab
Intratumoral injection of a single dose of VSV-IFNß-NIS and intravenous infusion of avelumab

Locations

Country	Name	City	State
United States	Nationwide Children's Hospital	Columbus	Ohio
United States	Mary Crowley Cancer Research Center	Dallas	Texas
United States	University of Miami	Miami	Florida
United States	Masonic Cancer Center, University of Minnesota	Minneapolis	Minnesota
United States	Sarah Cannon Research Institute	Nashville	Tennessee
United States	Sanford Cancer Center	Sioux Falls	South Dakota

Sponsors (1)

Lead Sponsor	Collaborator
Vyriad, Inc.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Maximum Tolerated Dose (MTD) of VSV-IFNß-NIS Monotherapy and Combination Therapy		21 days after VSV-IFNß-NIS Monotherapy or Combination Therapy for each dose cohort