Intratumoral CAVATAK (CVA21) and Ipilimumab in Patients With Advanced Melanoma (VLA-013 MITCI)

Study Overview
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Brief Summary
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Open label, single arm study of intratumoral CVA21 and ipilimumab in advanced melanoma patients.

Detailed Description
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Primary Objective: To evaluate the safety and efficacy of CAVATAK (CVA21) administered intratumorally in combination with the approved dose and schedule of ipilimumab. Of particular interest is to estimate the overall response rate (ORR) in the subgroup of subjects with unresectable or metastatic stage III B/C or IV melanoma who have progressed on a single prior anti-PD-1 therapy. Secondary Objectives: Assess the clinical efficacy of ipilimumab in combination with intratumoral CVA21 in terms of: Immune-related progression-free survival (irPFS) at 6 and 12 months, Durable response rate (DRR), 1-year survival, Overall survival (OS), and Quality of life. Assess the response of injected and non-injected melanoma lesions after CVA21 and ipilimumab. Assess the time to initial response.

Official Title
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A PHASE 1b STUDY OF INTRATUMORAL CAVATAK® (COXSACKIEVIRUS A21, CVA21) AND IPILIMUMAB IN PATIENTS WITH ADVANCED MELANOMA (VLA-013 MITCI)

Conditions
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Melanoma

Intervention / Treatment
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* Biological: CAVATAK
* Drug: Ipilimumab


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients with unresectable or metastatic stage III B/C or IV melanoma. Patients enrolled under this version of the protocol must also have progressed on prior anti-PD-1 therapy, according to RECIST 1.1 criteria. Patients who progressed within 3 months of treatment start are excluded. Patients must have at least one cutaneous or subcutaneous tumor, measuring 0.5 to 5.0 cm in the longest diameter, or a palpable lymph node. At least one tumor must qualify as an index lesion that can be accurately and reproducibly measured in two dimensions for which the longest diameter is .10 mm (.15 mm in short axis diameter [SAD] for lymph nodes), and be amenable to intratumoral injection. Histological confirmation of melanoma will be required by previous biopsy or cytology. Patients who have received prior ipilimumab treatment for metastatic melanoma are not eligible. Patients with ≤ 3 visceral metastases (excluding pulmonary lesions), with no lesions >3.0 cm. Patients with substantial tumor burden of non-measurable disease may not be good candidates for an immunotherapy and should be discussed with the Medical Monitor. 7. ECOG performance status of 0-1. Key Exclusion Criteria: Patients with tumors to be injected lying close to an airway, major blood vessel or spinal cord that, in the opinion of the Investigator, could cause occlusion or compression in the case of tumor swelling or erosion into a major vessel in the case of necrosis. Patients with lesions in mucosal areas (vulvar, anus, oral cavity, etc.), are eligible, as long as the subject has at least one lesion suitable for injection; consult Medical Monitor for confirmation. Patients with active, known or suspected autoimmune disease except for autoimmune thyroiditis or vitiligo. Thyroiditis patients must be asymptomatic, on adequate thyroid replacement and have normal thyroid function tests. Patients with active colitis or immune-mediated colitis that has not resolved to grade 1 or less. Patients with untreated brain metastases. Patients with treated brain metastases who are off corticosteroids for at least two weeks and who demonstrate control of brain metastases with follow-up imaging 4 or more weeks after initial therapy are eligible. Patients previously treated with CVA21.

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 ipilimumab<br>CAVATAK intratumoral injection up to a total dose of 3 x 10⁸ TCID50 and ipilimumab intravenously at the recommended dose of 3 mg/kg | Biological: CAVATAK<br>* CAVATAK is a preparation of CVA21<br>* Other names: Coxsackievirus A21, CVA21;Drug: Ipilimumab<br>* Ipilimumab is a human cytotoxic T-lymphocyte antigen (CTLA-4)-blocking antibody indicated for the treatment of unresectable or metastatic melanoma<br>* Other names: Yervoy®;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Response | Best response of complete response (CR) or partial response (PR) | 106 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| DRR | Durable Response Rate | lasting 26 weeks or longer | 
| PFS | Progression-Free Survival | At 6 and 12 months | 
| OS | Overall | Through study completion, an average of 2 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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CAVATAK, melanoma, ipilimumab, coxsackievirus A21, CVA21, checkpoint inhibitors