Clinical trial NCT02923466: Ph1 Administration of VSV-IFNβ-NIS Monotherapy and in Combination With Avelumab in Pts With Refractory Solid Tumors
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Malignant Solid Tumour
Keywords: refractory solid tumor
Lead sponsor: Vyriad, Inc.
Sponsor class: INDUSTRY
First posted: 2016-10-04
Enrollment: 76
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Maximum Tolerated Dose (MTD) of VSV-IFNβ-NIS Monotherapy and Combination Therapy
timeFrame: 21 days after VSV-IFNβ-NIS Monotherapy or Combination Therapy for each dose cohort
Secondary outcomes:
Other outcomes:
Locations:
city: Miami
country: United States
facility: University of Miami
state: Florida
city: Minneapolis
country: United States
facility: Masonic Cancer Center, University of Minnesota
state: Minnesota
city: Columbus
country: United States
facility: Nationwide Children's Hospital
state: Ohio
city: Sioux Falls
country: United States
facility: Sanford Cancer Center
state: South Dakota
city: Nashville
country: United States
facility: Sarah Cannon Research Institute
state: Tennessee
city: Dallas
country: United States
facility: Mary Crowley Cancer Research Center
state: Texas
Study officials:
affiliation: CMO
name: Alice Bexon, MD
role: PRINCIPAL_INVESTIGATOR
References: