Ph I/II Trial of Systemic VSV-IFNβ-NIS in Combination With Checkpoint Inhibitor Therapy in Patients With Select Solid Tumors

Part of paid clinical trials in Rochester, Minnesota.

Sponsor
Vyriad, Inc.
Study ID
NCT03647163
Phase
PHASE1/PHASE2
Status
Active Not Recruiting

Conditions

Eligibility Criteria

Sex
ALL
Age
18 Years - N/A
Healthy Volunteers
Not accepted

Interventions

  • VSV-IFNβ-NIS — BIOLOGICAL
    Intravenous oncolytic Vesicular stomatitis virus (VSV) expressing Interferon-beta (IFNβ) and the sodium iodide symporter (NIS)
  • Pembrolizumab — BIOLOGICAL
    Pembrolizumab
  • ipilimumab + nivolumab — BIOLOGICAL
    Intravenous ipilimumab 1mg/kg in combination with nivolumab 360mg, or Intravenous ipilimumab 1mg/kg in combination with nivolumab 3mg/ kg for 4 cycles, followed by fixed dose nivolumab 480mg

Study Details

The safety run-in portion of this study is designed to identify the optimal dose of VSV-IFNβ-NIS in combination with pembrolizumab in patients with solid tumors and follows the 3+3 design. The expansion portion will use one-sample binomial designs to assess the efficacy of the combination in patients with refractory NSCLC or NEC. The optimal dose (RP2D) determined in the dose escalation portion of the trial will be used for the expansion portion. The study has been conducted with a dose of 1.7 × 1010 as the recommended phase II dose in an expansion cohort of 10 patients with NSCLC. However, current data suggests that VSV-IFNβ-NIS doses of up to 1.7 × 1011 is safe and likely more efficacious. Thus, this study will test a second VSV-IFNβ-NIS dose level, 1.0x1011 TCID50. A safety assessment will be carried out after 3 patients are enrolled. If this dose schedule is well tolerated and virus PK are not negatively impacted, both the NSCLC and NEC expansion cohorts will open using this dose schedule. If 2 of the first 3 patients or 2 of the first 6 patients experience a DLT, the dose will be de-escalated to 5 x 1010. The safety run-in/dose escalation portion of this study is expected to require a minimum of 3 patients and a maximum of 18 patients (6 patients per dose level). The expansion portion of this study is expected to require a minimum of 10 per cohort. The NSCLC and NEC patients enrolled at the identified optimal dose in the dose escalation cohort would be included in the dose expansion cohort if they are evaluable for the primary endpoint in the expansion portion (4 dose escalation patients at the optimal dose are expected to roll over to the expansion). Additionally, up to 16 Renal Cell Carcinoma (RCC) patients will be treated in the expansion cohort. This will permit up to 86 treated patients.

Key Dates

Start date
Apr 9, 2019
Status verified
Sep 2025
Primary completion
Jul 31, 2025
Completion
Sep 30, 2025

Study Design

Enrollment
33 participants (actual)
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT

Arms

  • Experimental: Safety Run-in Dose Level 1
    Patients with pembrolizumab refractory solid tumors will receive a single IV dose of 5e10 TCID50 VSV-IFNβ-NIS in combination with Pembrolizumab at standard labeled dose administered on day 1, then every 21 days, up to 2 years.
  • Experimental: Safety Run-in Dose Level 2
    Patients with pembrolizumab refractory Neuroendocrine Carcinoma (NEC) or non small cell lung cancer (NSCLC) will receive a single IV dose of 1.0e11 TCID50 VSV-IFNβ-NIS in combination with Pembrolizumab at standard labeled dose administered on day 8, then every 21 days, up to 2 years.
  • Experimental: Expansion NEC
    Patients with pembrolizumab refractory Neuroendocrine Carcinoma (NEC) will receive a single IV dose of 1.0e11 TCID50 VSV-IFNβ-NIS in combination with Pembrolizumab at standard labeled dose administered on day 8, then every 21 days, up to 2 years.
  • Experimental: Expansion NSCLC arm
    Patients with pembrolizumab refractory non small cell lung cancer (NSCLC) will receive a single IV dose of 1.0e11 TCID50 VSV-IFNβ-NIS in combination with Pembrolizumab at standard labeled dose administered on day 8, then every 21 days, up to 2 years.
  • Experimental: Expansion Part D
    Patients with non small cell lung cancer (NSCLC) or Neuroendocrine Carcinoma (NEC) will receive a single IV dose of VSV-IFNβ-NIS on Day 4 in combination with ipilumumab + nivolumab at standard labeled dose administered on Day 1 then every 21 days up to 2 years.
  • Experimental: Expansion Renal Cell Carcinoma (RCC) Part E
    Arm Description: Renal Cell Carcinoma (RCC) will receive a single IV dose of VSV-IFNβ-NIS on Day 4 in combination with ipilumumab + nivolumab at standard labeled dose administered on Day 1 then every 21 days for a total of 4 Cycles. Nivo Single agent will be administered every 28 days starting with Cycle 5 for a total treatment period of up to 2 years.

Primary Outcome Measure

Expansion arms: Overall response rate (ORR) [ Time Frame: 43 days - 6 months ]

Locations (2)

FacilityCityStateZIPSite coordinators
Mayo ClinicRochesterMinnesota55905-
Cleveland Clinic Taussig Cancer InstituteClevelandOhio44195-

Find similar trials in Rochester, MN

By condition
Neuroendocrine tumorsLung cancer
By specialty
OncologyLung oncologyLung disease
By research site
Mayo Clinic· Rochester, MNCleveland Clinic Taussig Cancer Institute· Cleveland, OH

Related Studies