Neoplasms

Skin and Connective Tissue Diseases

All Conditions

Infections

Rare Diseases

Melanoma

Coxsackievirus Infections

Neuroendocrine Tumors

Neuroectodermal Tumors

Neuroectodermal Tumors, Primitive

Neoplasms, Germ Cell and Embryonal

Neoplasms by Histologic Type

Neoplasms, Nerve Tissue

Nevus, Pigmented

Nevus

Nevi and Melanomas

Skin Neoplasms

Skin Diseases

Neuroendocrine Tumor

Neuroepithelioma

All Drugs and Chemicals

Antineoplastic Agents

Antibodies

Ipilimumab

Immunoglobulins

Antibodies, Blocking

Antineoplastic Agents, Immunological

Immune Checkpoint Inhibitors

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

Ipilimumab is a human cytotoxic T-lymphocyte antigen (CTLA-4)-blocking antibody indicated for the treatment of unresectable or metastatic melanoma

Brendan Curti, MD

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

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.

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

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

http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf

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

Providence Health & Services

Viralytics

Pharmaceutical Solutions

Pembrolizumab

Intratumoral CAVATAK administration on trial days 1, 3, 5 and 8 and at 3-weekly intervals up to a maximum of 19 total with intravenous pembrolizumab (2 mg/kg solution) starting on day 8 and continuing every 3 weeks, up to 2 years.

Maximum dose of CVA21 is 3 x 10E+08 TCID50 (about 4.5 x 10E+06 TCID50/kg for a 70-kg patient) by intratumoral administration.

Intravenous pembrolizumab at 2 mg/kg solution.

This study will employ a phase Ib design using the established dose of CAVATAK with pembrolizumab in subjects with advanced melanoma for whom pembrolizumab would be considered standard of care. Our hypothesis is that oncolysis of melanoma cells by CAVATAK will be important in amplifying the T-cell potentiating effects of pembrolizumab.

Intratumoral CAVATAK (CVA21) and Pembrolizumab in Patients With Advanced Melanoma (VLA-011 CAPRA)

Phase I Study of Intratumoral CAVATAK® (Coxsackievirus A21) and Pembrolizumab in Subjects With Advanced Melanoma (VLA-011 CAPRA)

Carcinoma

Carcinoma, Squamous Cell

Squamous Cell Carcinoma of Head and Neck

Head and Neck Neoplasms

1, 3 or 6 doses of CAVATAK (10\^9 TCID50) at 48 hour intervals.

CVA21

Stephen Ackland, MBBS FRACP

This study is designed to assess the safety and initial indications of efficacy resulting from multiple doses of CAVATAK injected directly into solid tumours of the Head and Neck that have been confirmed to express ICAM-1 and DAF.

CAVATAK (Coxsackievirus A21) is a naturally occurring common cold virus that preclinical research indicates can preferentially infect and kill cancer cells expressing the receptors ICAM-1 and/or DAF. This virus is known to cause self limiting upper respiratory infections and has been used previously to challenge therapies against the common cold. The virus is not generically modified.

The study proposes to administer CAVATAK to three cohorts each of three patients. The first cohort will receive a single dose, the second cohort will receive three doses, and the final cohort will receive six doses. There will a 48 hour interval between repeated doses.

The primary objective of the study is to determine the safety and efficacy of CVA21 given by intratumoural injection in the treatment of recurrent, unresectable squamous cell carcinoma of the head and neck by measuring primary and field tumour status and adverse effects.

Secondary objectives of the study are:

1. Indirect measurements of efficacy by measuring appropriate biomarkers in serum and tumour biopsy samples for viral replication, induction of apoptosis and anti-tumour immune responses.
2. To determine the time course of potential primary and secondary viraemia.
3. To characterise the time course of the anti-CVA21 antibody response after administration of CVA21

A Study of the Intratumoural Administration of CAVATAK to Head and Neck Cancer Patients (VLA-X06)

A Phase I, Open-label, Dosage Escalation, Study of Multiple Doses of CAVATAKTM (CVA21; Coxsackievirus A21) Administered Intratumourally in the Treatment of Squamous Cell Carcinoma of the Head and Neck Bearing ICAM-1 Receptors (VLA-X06)

Symptoms and General Pathology

Communicable Diseases

Enterovirus Infections

Picornaviridae Infections

Virus Diseases

RNA Virus Infections

Coxsackievirus A21

The purpose of this study is to determine the safety of an injection of coxsackievirus A21 into a melanoma tumour, and also to see if there is a tumour response.

Coxsackievirus A21, a naturally occurring enterovirus, has shown that in vivo it can infect and lyse melanoma. This study is to assess safety of a single intratumoural injection of the virus into an accessible subcutaneous melanoma metastasis.

Intratumoural Administration of Coxsackievirus A21 for the Control of Malignant Melanoma (PXS-X02)

The purpose of the study is to determine the safety and tolerability of two doses of Coxsackievirus A21, administered 48 hours apart into a superficial melanoma tumour.

Injected and non-injected tumours will be observed regarding change in tumour size.

Coxsackievirus A21 (CVA21) is a naturally occurring virus, that is known to cause self limiting upper respiratory infections. CVA21 has been shown in cell culture to infect and kill human melanoma cancer cell lines. This property of CVA21 is due to the specific receptors CVA21 uses in order to attach to, and infect a cell. The 2 receptors CVA21 uses to infect a cell are Intracellular Adhesion Molecule 1 (ICAM-1) and Decay Accelerating Factor. Both of these surface proteins are expressed on melanoma cell lines as well as human melanoma tumours. Animal models of human melanoma tumours have demonstrated that CVA21 injection either intratumour or intravenous causes infection in the tumours, resulting in reduction of tumour size and growth.

A Safety Study of Two Intratumoural Doses of Coxsackievirus Type A21 in Melanoma Patients (PSX-X03)

A Phase I, Open Label, Cohort Study of Two Doses of Cavatak (Coxsackievirus Type A21) Given Intratumourally in Stage IV Melanoma Patients.

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Urinary Bladder Neoplasms

Non-Muscle Invasive Bladder Neoplasms

Urologic Neoplasms

Urogenital Neoplasms

Urogenital Diseases

Female Urogenital Diseases

Pregnancy Complications

Female Urogenital Diseases and Pregnancy Complications

Urinary Bladder Diseases

Urologic Diseases

Male Urogenital Diseases

Neoplasms, Glandular and Epithelial

Anti-Infective Agents

Mitomycins

Mitomycin

Anti-Bacterial Agents

Antibiotics, Antitubercular

Alkylating Agents

Enzyme Inhibitors

CVA21 was administered by intravesical instillation at one of three (3) ascending dose levels or schedules.

Mitomycin C (MMC) was administered at 10 mg by intravesical instillation on Day 1. Four hours after instillation of MMC, CVA21 was administered by intravesical instillation of one of 2 ascending dose levels or schedules. Subjects received a second instillation of CVA21 alone on Day 2 without pretreatment with MMC.

CAVATAK is a purified preparation of CVA21

Mitomycin C

Hardev Pandha

The study consisted of 2 sequential parts. Part A assessed the safety and tolerability of CAVATAK administered via intravesical instillation in patients with non-muscle invasive bladder cancer scheduled to undergo TUR. Part B assessed the safety and tolerability of CAVATAK administered in sequential combination with low dose Mitomycin C in the same patient population.

This was a Phase I, two-part, open-label, dose-escalation study designed to evaluate CVA21 alone and in sequential combination with low-dose mitomycin C in patients with non-muscle invasive bladder cancer (NMIBC) who were candidates for and were planning to undergo TUR for treatment of their disease. This gave a relatively homogeneous study population and facilitated collection of resected tumour tissue for histological, pharmacodynamics (PD) and pharmacokinetic (PK) analyses.

CAVATAK (CVA21) in Non-muscle Invasive Bladder Cancer (VLA-012 CANON)

A Phase 1 Study to Evaluate the Safety and Clinical Activity of Intravesicular CAVATAK (Coxsackievirus A21, CVA21) Alone and in Sequential Combination With Low Dose Mitomycin C in Patients With Non-Muscle Invasive Bladder Cancer (VLA-012 CANON)

Number of Participants with Treatment-emergent adverse events. The events for each cohort of dose of CVA21 only are pooled for the analysis.

No SUSARs were reported for the VLA-012 study.

CVA21 was administered by intravesical instillation of one of 3 ascending dose levels or schedules

CVA21/Mitomycin C

CVA21 was administered by intravesical instillation of one of 3 ascending dose levels or schedules:

Mitomycin C (MMC) was administered at 10 mg by intravesical instillation on Day 1. Four hours after instillation of MMC, CVA21 was administered by intravesical instillation of one of 2 ascending dose levels or schedules. Subjects received a second instillation of CVA21 alone on Day 2 without pretreatment with MMC

CVA21/MitomycinC

Total

Age, Continuous

Sex: Female, Male

Ethnicity (NIH/OMB)

Small number of subjects with limited follow-up; study not designed to give any indication of efficacy. The analysis for each dose escalation cohort for CVA21 only was pooled as the numbers were so small. This resulted in an analysis showing 2 arms.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Intratumoral CAVATAK (CVA21) and Ipilimumab in Patients With Advanced Melanoma (VLA-013 MITCI)	NCT02307149	Melanoma	CAVATAK Ipilimumab	18 Years -	Viralytics
Intratumoral CAVATAK (CVA21) and Ipilimumab in Patients With Advanced Melanoma (VLA-013 MITCI)	NCT02307149	Melanoma	CAVATAK Ipilimumab	18 Years -	Viralytics
Intratumoral CAVATAK (CVA21) and Pembrolizumab in Patients With Advanced Melanoma (VLA-011 CAPRA)	NCT02565992	Melanoma	CAVATAK Pembrolizumab	18 Years -	Viralytics
A Study of the Intratumoural Administration of CAVATAK to Head and Neck Cancer Patients (VLA-X06)	NCT00832559	Head and Neck C...	CVA21	18 Years -	Viralytics
Intratumoural Administration of Coxsackievirus A21 for the Control of Malignant Melanoma (PXS-X02)	NCT00235482	Malignant Melan...	Coxsackievirus ...	21 Years - 70 Years	Viralytics
A Safety Study of Two Intratumoural Doses of Coxsackievirus Type A21 in Melanoma Patients (PSX-X03)	NCT00438009	Stage IV Melano...	Coxsackievirus ...	18 Years -	Viralytics
CAVATAK (CVA21) in Non-muscle Invasive Bladder Cancer (VLA-012 CANON)	NCT02316171	Non-muscle Inva...	CVA21 Mitomycin C	18 Years -	Viralytics

Spots Global Cancer Trial Database for coxsackievirus a21