Dose Escalation Trial of Intra-Tumoral Injection of NIS Measles Virus in Combination With Atezolizumab

Study Overview
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Brief Summary
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This a Phase 1 study designed to determine the maximum tolerated dose (MTD) and toxicity of attenuated Measles virus (MV-NIS) combined with Atezolizumab in patients with recurrent and metastatic NSCLC.

Detailed Description
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Phase 1, dose escalation study of the combination of intra-tumoral MV-NIS and systemic atezolizumab in patients with recurrent and metastatic NSCLC. After the dose escalation phase of the trial, a dose expansion cohort was planned to further investigate safety, clinical and immune responses at the MTD. A standard 3+3 design was to be used for the dose escalation part of the study. Starting at dose level 1, three patients were to be treated per dose level. MV-NIS was to be administered once intra-tumorally (IT) on Day 1 of treatment in 3 escalating dose cohorts, starting at dose level 1 x 10e8

Official Title
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Phase 1 Dose Escalation Trial of Intra-Tumoral Injection of Sodium Iodide Simporter (NIS) Measles Virus (Edmonston Strain) in Combination With Atezolizumab in Patients With Metastatic Non-Small Cell Lung Cancer (NSCLC)

Conditions
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Recurrent Non-Small Cell Lung Cancer

Intervention / Treatment
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* Biological: MV-NIS
* Biological: Atezolizumab


Participation Criteria
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Eligibility Criteria
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Key Inclusion Criteria: Diagnosis of metastatic lung cancer, with histologic confirmation of the primary NSCLC histology and with at least one lesion amenable for intra-tumoral injection of MV-NIS. Patient meets the FDA-approved indication for Atezolizumab treatment in NSCLC. Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) 0 or 1. Ability to provide informed consent. Adequate hematological, liver and kidney function. Must be willing to implement contraception throughout study and for the 8 weeks following last study drug administration. Key Exclusion Criteria: Any of the following prior therapy: Chemotherapy ≤ 3 weeks prior to registration. Biologic therapy ≤ 4 weeks prior to registration. Radiation therapy ≤ 3 weeks prior to registration Other concurrent investigational therapy (utilized for a non-FDA-approved indication and in the context of a research investigation). Pregnant women. Nursing women. Men or women of childbearing potential who are unwilling to employ adequate contraception during treatment and 8 weeks following the completion of study drug treatment. Allergy to measles vaccine or history of severe reaction to prior measles vaccination. History of organ transplantation.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: MV-NIS and Atezolizumab<br>MV-NIS will be administered intratumorally as a single dose on day 1. Atezolizumab will be given at day 15 and then every 3 weeks. | Biological: MV-NIS<br>* This is an open label single ascending dose phase I study designed to determine the safety profile and MTD after IT administration of a single dose of MV-NIS in combination with Atezolizumab in patients with metastatic NSCLC<br>Biological: Atezolizumab<br>* Atezolizumab will be administered every 3 weeks<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum Tolerated Dose (MTD) of MV-NIS in Combination With Atezolizumab | To determine the maximum tolerated dose (MTD) of the intra-tumoral administration of an Edmonston strain MV genetically engineered to produce NIS (MV-NIS), in combination with the PD-L1 inhibitor atezolizumab | 28 days after MV-NIS administration for each dose cohort | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Lung Cancer Measles Nivolumab Opdivo