Clinical trial NCT02307149: 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)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Melanoma
Keywords: melanoma
ipilimumab
coxsackievirus A21
CAVATAK
CVA21
checkpoint inhibitors
Lead sponsor: Viralytics
Sponsor class: INDUSTRY
Collaborators: name: Providence Health & Services
First posted: 2014-12-04
Enrollment: 50
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: Response
timeFrame: 106 days
Secondary outcomes:
measure: DRR
timeFrame: lasting 26 weeks or longer
measure: PFS
timeFrame: At 6 and 12 months
measure: OS
timeFrame: Through study completion, an average of 2 years
Other outcomes:
Locations:
city: Duarte
country: United States
facility: City of Hope National Medical Center,
state: California
city: La Jolla
country: United States
facility: UC San Diego Moores Cancer Center
state: California
city: Los Angeles
country: United States
facility: The Angeles Clinic & Research Institute
state: California
city: Santa Monica
country: United States
facility: John Wayne Cancer Institute
state: California
city: Miami
country: United States
facility: Sylvester Comprehensive Cancer Center
state: Florida
city: Park Ridge
country: United States
facility: Advocate Health, SC
state: Illinois
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Boston
country: United States
facility: Dana Farber Cancer Institute
state: Massachusetts
city: Morristown
country: United States
facility: Atlantic Melanoma Center
state: New Jersey
city: Portland
country: United States
facility: Providence Portland Medical Center
state: Oregon
city: Salt Lake City
country: United States
facility: Huntsman Cancer Institute
state: Utah
Study officials:
affiliation: Providence Health & Services
name: Brendan Curti, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.