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.
Active, not recruiting
Phase 1
| Drug | Synonyms | Arms |
|---|---|---|
| VSV-IFNβ-NIS | Selection of VSV-IFNβ-NIS Monotherapy | |
| VSV-IFNβ-NIS and avelumab | VSV-IFNβ-NIS and avelumab |
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.
| Name | Type | Description | Interventions |
|---|---|---|---|
| VSV-IFNβ-NIS | Experimental | VSV-IFNβ-NIS will be administered intratumorally as a single dose on day 1. |
|
| Selection of VSV-IFNβ-NIS Monotherapy | Experimental | VSV-IFNβ-NIS will be administered either intratumorally, intravenously or with a combination of intratumorally and intravenously as a single dose on day 1. |
|
| VSV-IFNβ-NIS and avelumab | Experimental | 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. |
|
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.
| Maximum Eligible Age: | N/A |
| Minimum Eligible Age: | 18 Years |
| Eligible Gender: | All |
| Healthy Volunteers: | No |
| Measure: | 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 |
| Safety Issue: | |
| Description: |
| Phase: | Phase 1 |
| Primary Purpose: | Interventional |
| Overall Status: | Active, not recruiting |
| Lead Sponsor: | Vyriad, Inc. |
July 7, 2021
