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

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

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

Study Overview

• Status: Completed
• Conditions: Melanoma
• Intervention / Treatment: Biological: CAVATAK; Drug: Ipilimumab

Detailed Description

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:

1. 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.
2. Assess the response of injected and non-injected melanoma lesions after CVA21 and ipilimumab.
3. Assess the time to initial response.

• Study Type: Interventional
• Enrollment (Actual): 50
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • California
    • Duarte, California, United States, 91010
      • City of Hope National Medical Center,
    • La Jolla, California, United States, 92093
      • UC San Diego Moores Cancer Center
    • Los Angeles, California, United States, 90025
      • The Angeles Clinic & Research Institute
    • Santa Monica, California, United States, 90404
      • John Wayne Cancer Institute
  • Florida
    • Miami, Florida, United States, 33136
      • Sylvester Comprehensive Cancer Center
  • Illinois
    • Park Ridge, Illinois, United States, 60068
      • Advocate Health, SC
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Massachusetts General Hospital
    • Boston, Massachusetts, United States, 02215
      • Dana Farber Cancer Institute
  • New Jersey
    • Morristown, New Jersey, United States, 07960
      • Atlantic Melanoma Center
  • Oregon
    • Portland, Oregon, United States, 97213
      • Providence Portland Medical Center
  • Utah
    • Salt Lake City, Utah, United States, 84112
      • Huntsman Cancer Institute

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. 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.
2. 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.
3. Histological confirmation of melanoma will be required by previous biopsy or cytology.
4. Patients who have received prior ipilimumab treatment for metastatic melanoma are not eligible.
5. 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:

1. 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.
2. 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.
3. Patients with active colitis or immune-mediated colitis that has not resolved to grade 1 or less.
4. 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.
5. Patients previously treated with CVA21.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: CAVATAK and ipilimumab; 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; CAVATAK is a preparation of CVA21; Other Names: Coxsackievirus A21, CVA21; Drug: Ipilimumab; Ipilimumab is a human cytotoxic T-lymphocyte antigen (CTLA-4)-blocking antibody indicated for the treatment of unresectable or metastatic melanoma; Other Names: Yervoy®

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Viralytics
• Collaborators: Providence Health & Services

Publications and helpful links

General Publications

• Curti BD, Richards J, Hyngstrom JR, Daniels GA, Faries M, Feun L, Margolin KA, Hallmeyer S, Grose M, Zhang Y, Li A, Andtbacka RHI. Intratumoral oncolytic virus V937 plus ipilimumab in patients with advanced melanoma: the phase 1b MITCI study. J Immunother Cancer. 2022 Dec;10(12):e005224. doi: 10.1136/jitc-2022-005224.

Study record dates

Study Major Dates

• Study Start (Actual): May 5, 2015
• Primary Completion (Actual): November 5, 2019
• Study Completion (Actual): November 5, 2019

Study Registration Dates

• First Submitted: November 26, 2014
• First Submitted That Met QC Criteria: December 2, 2014
• First Posted (Estimate): December 4, 2014

Study Record Updates

• Last Update Posted (Estimate): January 16, 2023
• Last Update Submitted That Met QC Criteria: January 12, 2023
• Last Verified: January 1, 2023

More Information

Terms related to this study

• Keywords: CVA21; CAVATAK; melanoma; checkpoint inhibitors; ipilimumab; coxsackievirus A21
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Neuroendocrine Tumors; Nevi and Melanomas; Melanoma; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Antineoplastic Agents, Immunological; Immune Checkpoint Inhibitors; Ipilimumab
• Other Study ID Numbers: V937-009; PHS IRB: 14-241 (Other Identifier: Providence Health & Services); VLA-013 (Other Identifier: Viralytics Study ID)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes
• IPD Plan Description: http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf