Intratumoral CAVATAK (CVA21) and Pembrolizumab in Patients With Advanced Melanoma (VLA-011 CAPRA)

Study Overview
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Brief Summary
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This study will employ a phase Ib design using the established dose of CAVATAK with pembrolizumab in subjects with advanced melanoma for whom pembrolizumab would be considered standard of care. Our hypothesis is that oncolysis of melanoma cells by CAVATAK will be important in amplifying the T-cell potentiating effects of pembrolizumab.

Official Title
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Phase I Study of Intratumoral CAVATAK® (Coxsackievirus A21) and Pembrolizumab in Subjects With Advanced Melanoma (VLA-011 CAPRA)

Conditions
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Melanoma

Intervention / Treatment
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* Biological: CAVATAK
* Drug: Pembrolizumab


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subjects with metastatic or unresectable stage IIIb/c of IV melanoma for whom treatment with pembrolizumab is indicated and who have at least one cutaneous, subcutaneous tumor or palpable lymph node amenable to intratumoral injection. At least one tumor must qualify to be an index lesion for modified WHO criteria. Subjects must have adequate hematologic, hepatic and renal function. ECOG performance status of 0 or 1. Anticipated lifespan greater than 12 weeks Exclusion Criteria: Ocular primary tumors. Presence of any central nervous system tumor that has not been stable for at least 4 weeks off corticosteroids. Tumors lying in mucosal regions or close to an airway, major blood vessel or spinal cord. Subjects with active, known or suspected autoimmune or immunosuppressive disease. Subjects previously treated with CVA21. Subjects requiring systemic treatment with corticosteroids or other immunosuppressive medications within 14 days prior to the first treatment. Subject has received chemotherapy within the last 4 weeks prior to first treatment. Clinically significant cardiovascular disease. Females of childbearing potential must have negative serum or urine pregnancy test. Subjects requiring or using other investigational agents while on treatment in this trial. History of other malignancy within the last 3 years (with exceptions). Active infection requiring systemic therapy. Known history of HIV disease, active hepatitis B or hepatitis C. History or evidence of other clinically significant disorders that would pose a risk to subject safety. Inability to give informed consent and comply with the protocol.

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: CAVATAK and pembrolizumab<br>Intratumoral CAVATAK administration on trial days 1, 3, 5 and 8 and at 3-weekly intervals up to a maximum of 19 total with intravenous pembrolizumab (2 mg/kg solution) starting on day 8 and continuing every 3 weeks, up to 2 years. | Biological: CAVATAK<br>* Maximum dose of CVA21 is 3 x 10E+08 TCID50 (about 4.5 x 10E+06 TCID50/kg for a 70-kg patient) by intratumoral administration.<br>* Other names: Coxsackievirus A21, CVA21;Drug: Pembrolizumab<br>* Intravenous pembrolizumab at 2 mg/kg solution.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The incidence of dose-limiting toxicities (DLT) of intravenous pembrolizumab in combination with intratumoral CAVATAK will be assessed using CTCAE v. 4.0. |  | Up to 2 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Pembrolizumab, Coxsackievirus A21, melanoma, CAVATAK, CVA21, checkpoint inhibitor