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

Phase 1

Completed

• Conditions: Melanoma
• Interventions: Biological: CAVATAK; Drug: Ipilimumab

• Registration Number: NCT02307149
• Lead Sponsor: Viralytics

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 Timeline

• Study First Submitted: 2014-11-26
• Study First Submitted QC: 2014-12-02
• Study First Posted: 2014-12-04
• Study Start: 2015-05-05
• Primary Completion: 2019-11-05
• Study Completion: 2019-11-05
• Status Verified: 2023-01
• Last Update Submitted: 2023-01-12
• Last Update Posted: 2023-01-17

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 50

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.

6. 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 & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
CAVATAK and ipilimumab	CAVATAK	CAVATAK intratumoral injection up to a total dose of 3 x 10⁸ TCID50 and ipilimumab intravenously at the recommended dose of 3 mg/kg
CAVATAK and ipilimumab	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

Primary Outcome Measures

Name	Time	Method
Response	106 days	Best response of complete response (CR) or partial response (PR)

Secondary Outcome Measures

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

Trial Locations

Locations (11)

The Angeles Clinic & Research Institute; 🇺🇸 Los Angeles, California, United States

Sylvester Comprehensive Cancer Center; 🇺🇸 Miami, Florida, United States

Advocate Health, SC; 🇺🇸 Park Ridge, Illinois, United States

Massachusetts General Hospital; 🇺🇸 Boston, Massachusetts, United States

Dana Farber Cancer Institute; 🇺🇸 Boston, Massachusetts, United States

Providence Portland Medical Center; 🇺🇸 Portland, Oregon, United States

City of Hope National Medical Center,; 🇺🇸 Duarte, California, United States

UC San Diego Moores Cancer Center; 🇺🇸 La Jolla, California, United States

John Wayne Cancer Institute; 🇺🇸 Santa Monica, California, United States

Atlantic Melanoma Center; 🇺🇸 Morristown, New Jersey, United States

Huntsman Cancer Institute; 🇺🇸 Salt Lake City, Utah, United States