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

• ClinicalTrials.gov Identifier: NCT02307149
• Recruitment Status: Completed
• First Posted: December 4, 2014
• Last Update Posted: January 17, 2023
• Sponsor: Viralytics
• Collaborator: Providence Health & Services
• Information provided by (Responsible Party): Viralytics

Tracking Information

• First Submitted Date: November 26, 2014
• First Posted Date: December 4, 2014
• Last Update Posted Date: January 17, 2023
• Actual Study Start Date: May 5, 2015
• Actual Primary Completion Date: November 5, 2019 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: July 23, 2017)

Response [ Time Frame: 106 days ]

Best response of complete response (CR) or partial response (PR)

• Original Primary Outcome Measures (submitted: December 2, 2014): Safety/ tolerance of multiple intratumoral injections of CAVATAK when given in conjunction with ipilimumab as assessed by incidence of dose-limiting toxicities (DLT). [ Time Frame: Up to 106 days ]

Current Secondary Outcome Measures (submitted: July 23, 2017)

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

• Original Secondary Outcome Measures (submitted: December 2, 2014): Estimate the objective response rate to CAVATAK and ipilimumab in patients with metastatic melanoma using irRC-WHO criteria [ Time Frame: Up to 106 days ]
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Intratumoral CAVATAK (CVA21) and Ipilimumab in Patients With Advanced Melanoma (VLA-013 MITCI)
• Official Title: A PHASE 1b STUDY OF INTRATUMORAL CAVATAK® (COXSACKIEVIRUS A21, CVA21) AND IPILIMUMAB IN PATIENTS WITH ADVANCED MELANOMA (VLA-013 MITCI)
• Brief Summary: Open label, single arm study of intratumoral CVA21 and ipilimumab in advanced melanoma patients.

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
• Study Phase: Phase 1
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Melanoma

Intervention

• Biological: CAVATAK
  CAVATAK is a preparation of CVA21
  Other Name: 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 Name: Yervoy®

Study Arms

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

Interventions:

• Biological: CAVATAK
• Drug: Ipilimumab

• 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.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: January 14, 2020): 50
• Original Estimated Enrollment (submitted: December 2, 2014): 26
• Actual Study Completion Date: November 5, 2019
• Actual Primary Completion Date: November 5, 2019 (Final data collection date for primary outcome measure)

Eligibility Criteria

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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT02307149
• Other Study ID Numbers: V937-009; PHS IRB: 14-241 ( Other Identifier: Providence Health & Services ); VLA-013 ( Other Identifier: Viralytics Study ID )
• Has Data Monitoring Committee: Not Provided
• U.S. FDA-regulated Product: Not Provided

IPD Sharing Statement

• Plan to Share IPD: Yes
• Plan Description: http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf
• URL: http://engagezone.msd.com/ds_documentation.php

• Current Responsible Party: Viralytics
• Original Responsible Party: Same as current
• Current Study Sponsor: Viralytics
• Original Study Sponsor: Same as current
• Collaborators: Providence Health & Services

Investigators

• Principal Investigator: Brendan Curti, MD; Providence Health & Services

• PRS Account: Viralytics
• Verification Date: January 2023