CVA21 and Pembrolizumab in NSCLC & Bladder Cancer (VLA-009 STORM/ KEYNOTE-200)

Study Overview
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Brief Summary
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The purpose of this trial is to assess the ability of CVA21, either alone (Part A) or in combination with pembrolizumab (Part B), to reach and to replicate in existing tumors (while sparing normal cells) and to establish a safe multi-dose schedule of the virus for the treatment of solid tumors where enhanced expression of ICAM-1 and/ or DAF receptor occurs. This trial consists of 2 sequential parts: VLA-009 (Part A) conducted only in the UK and employed CVA21 as a monotherapy in NSCLC, castrate-resistant prostate cancer, melanoma and bladder cancer. VLA-009 (Part B) conducted in the US, AUS and UK employs CVA21 with pembrolizumab in NSCLC and bladder cancer. Both VLA-009A and VLA-009B are open-label, multi-center, ascending dose escalation (3+3 design) dose-finding and signal-seeking studies. Part A of the study is now complete and closed to enrolment. Part B is currently enrolling.

Official Title
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A Phase 1, Dose-finding and Signal-seeking Study of the Safety & Efficacy of Intravenous CAVATAK® Alone and in Combination With Pembrolizumab in Patients With Late Stage Solid Tumours (VLA-009 STORM / KEYNOTE-200)

Conditions
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Non-small Cell Lung Cancer, Bladder Cancer

Intervention / Treatment
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* Biological: CVA21/pembrolizumab


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologically-confirmed (1) NSCLC, (2) bladder cancer, (3) castrate-resistant prostate cancer which are metastatic, or (4) stage 3C or stage 4 melanoma. VLA009A: Locally advanced and/or metastatic disease for which curative surgery and/or radiation therapy is not possible and judged not to be a candidate for the current standard of care treatment. VLA009B: locally advanced and/or metastatic disease and judged to be a candidate for pembrolizumab to be used in combination with CVA21. All subjects in Cohort 3 or Phase 2 dose (P2D) must have a lesion accessible for FNA or core or open biopsy on day 8 of the first treatment cycle. No CVA21 neutralising antibody (≤ 1:16) Measurable or evaluable disease Exclusion Criteria: Second primary malignancy within the past 2 years (except non-melanoma skin cancer, in situ carcinoma of the cervix, breast cancer) Concurrent immunosuppressive therapy and no known immunosuppressive disease other than primary tumour

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: CVA21/pembrolizumab<br>CVA21/pembrolizumab | Biological: CVA21/pembrolizumab<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Response rate assessed according to immune-related RECIST 1.1 criteria |  | Up to 6 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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CAVATAK, KEYNOTE-200, pembrolizumab, lung cancer, bladder cancer