Neoplasms

Respiratory Tract (Lung and Bronchial) Diseases

All Conditions

Lung Neoplasms

Carcinoma, Non-Small-Cell Lung

Carcinoma

Carcinoma, Bronchogenic

Bronchial Neoplasms

Respiratory Tract Neoplasms

Thoracic Neoplasms

Lung Diseases

Respiratory Tract Diseases

All Drugs and Chemicals

Antineoplastic Agents

Antibodies

Antibodies, Monoclonal

Pembrolizumab

Immunoglobulins

Antineoplastic Agents, Immunological

Immune Checkpoint Inhibitors

CVA21 will be administered IV on days: 1, 3, 5, 8 29, 50, 71, 92, 113 134, and 155. 200mg Pembrolizumab will be administered as per normal dosing frequency at Q3W IV, and will continue for up to 24 months. Should dose limiting toxicities be observed participants may be transferred a lower dosage of CVA21.

Pembrolizumab is a selective monoclonal antibody that blocks the interaction between PD1 and its ligands PDL1 and PDL2, resulting in infiltration of tumour specific CD8+ T-cells and ultimately leads to tumour rejection.

CAVATAK is an oncolytic Coxsackie virus that specifically infects and kills ICAM overexpressing tumour cells

CVA21

Thomas John

This will be a Phase Ib open-label trial of CAVATAK™ (CVA21) in combination with Pembrolizumab for the treatment of patients with advanced NSCLC. The dose of Pembrolizumab will be fixed at 200mg. Three cohorts (dose levels) of intravenously-delivered CVA21 will be explored, using a standard 3+3 patient dose escalation design. The starting dose of CVA21 will be one log below the 1 x 10\^9 TCID50 dose found to be safe when CVA21 was given alone in an ongoing Phase I study (NCT02043665).

Primary Objective \& Hypothesis

(1) Objective:

To evaluate the safety of intravenous CVA21 in combination with pembrolizumab in patients with advanced NSCLC.

Hypothesis:

Pembrolizumab in combination with intravenous CVA21 will be well tolerated in patients with advanced NSCLC.

Secondary Objective \& Hypothesis

(1) Objective:

i. To evaluate the efficacy of intravenous CVA21 in inducing an immune cell rich tumour microenvironment in patients with a baseline biopsy demonstrating a tumour with an immune cell poor microenvironment.

ii. To evaluate the efficacy of intravenous CVA21 in combination with pembrolizumab in patients with advanced NSCLC using irRECIST.

iii. To evaluate the safety of intravenous CVA21 in combination with pembrolizumab.

iv. To identify a safe and potentially effective dose for intravenous CVA21 in combination with intravenous pembrolizumab.

v. To serially evaluate the presence of detectable virus and anti-viral antibodies in peripheral blood of the trial participants.

Hypothesis:

i. CVA21 will induce immune cell infiltration into tumors of patients that lack an immune cell rich micro-environment.

Pembrolizumab + CVA21 in Advanced NSCLC

A Phase I/II Open-label Trial of Intravenous CAVATAK^TM in Combination With Pembrolizumab for the Treatment of Patients With Advanced NSCLC

To evaluate the safety of intravenous CVA21 in combination with pembrolizumab in patients with advanced NSCLC. All adverse events will be collected and assessed with regards to CTCAE V4.0 grading, seriousness, duration and relationship to the study drugs.

Quantification of the Objective Response rate in patients on study by RECIST

The overall response according to the irRC is derived from time-point response assessments based on tumor burden. In the irRC, an immune-related Complete Response (irCR) is the disappearance of all lesions, measured or unmeasured, and no new lesions; an immune-related Partial Response (irPR) is a 50% drop in tumour burden from baseline as defined by the irRC; and immune-related Progressive Disease (irPD) is a 25% increase in tumour burden from the lowest level recorded. Everything else is considered immune-related Stable Disease (irSD).

Progression Free survival from first study treatment until end of study

Measurement of CVA21 virus and neutralizing antibodies at each CVA21 injection time point

Overall survival of patients on study from first study treatment.

PD-L1 expression will be measured using IHC from baseline and sequential biopsies

Merck Sharp & Dohme LLC

Viralytics

Olivia Newton-John Cancer Research Institute

Skin and Connective Tissue Diseases

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

Ipilimumab

Antibodies, Blocking

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

Pharmaceutical Solutions

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)

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Symptoms and General Pathology

Prostatic Neoplasms

Breast Neoplasms

Virus Diseases

Communicable Diseases

Genital Neoplasms, Male

Urogenital Neoplasms

Genital Diseases

Genital Diseases, Male

Urogenital Diseases

Prostatic Diseases

Male Urogenital Diseases

Enterovirus Infections

Picornaviridae Infections

RNA Virus Infections

IV administration of CVA21 in a dose escalation manner

IV infusion, dose escalation of one or two infusions of escalating strength

Boris Chern, MD

Winston Liauw, MD

Coxsackie A21 (CVA21) virus is to be administered by IV infusion to patients with Stage 4 melanoma, prostate and breast cancer. This is a dose escalation, safety study.

This is a phase I, multiple dose, dose escalation, open label, cohort study of three intravenous doses of Coxsackie virus A21 in patients with stage IV solid tumours. Prospective patients will attend the study centre for initial screening within 28 days prior to commencement of treatment. They will have the nature of the study and its procedures and risks fully explained. Patients must then sign an informed consent form giving permission for tumour testing before initial screening can be commenced.

Patients whose tumours test positive for ICAM-1 with or without DAF will attend the study centre for a further screening visit within 14 days prior to commencement of treatment. They will sign a full study informed consent form before any further screening procedures are carried out.

Patients who satisfy all inclusion and none of the exclusion criteria will commence the treatment stage, which consists of one or more doses of CVA21 administered by intravenous infusion as per the dosage escalation chart. The first 4 cohorts will be treated as in-patients. The follow up period will consist of 12 weeks, during which time patients will attend the trial centre for up to13 follow up visits to collect safety and efficacy data.

Coxsackie Virus A21 Administered Intravenously (IV) for Solid Tumour Cancers (PSX-X04)

A Phase I, Open-Label, Cohort Study of Multiple Doses of Cavatak™ (Coxsackie Virus A21) Given Intravenously to Stage IV Solid Tumour Cancer Patients Bearing ICAM-1 With or Without DAF Expressing Tumours (PSX-X04)

Dose of CAVATAK up to 3 x 10⁸ TCID50 for an additional 9 treatments at 3-week intervals

This is an extended use study for patients who have received 10 doses of CAVATAK™ in the VLA 007 trial. There may be patients who have benefitted from the study drug and who might benefit from further treatment. In order to accommodate those patients further treatment to complete 48 weeks of CVA21 intratumoral injections will be made available.

CAVATAK in Patients With Stage IIIc or IV Malignant Melanoma to Extend Dosing to 48 Weeks (VLA-008 CALM Ext)

A Phase 2 Study of the Efficacy and Safety of Intratumoral CAVATAK™ (Coxsackievirus A21, CVA21) in Patients With Stage IIIc and Stage IV Malignant Melanoma to Extend Dosing for up to 48 Weeks Total (VLA-008 CALM Ext)

Participants with Grade 3 or Higher Adverse Events

Listed serious adverse events (SAEs) and adverse events (AEs) are irrespective of treatment relationship. No SAEs reported were attributable to CVA21. No serious unexpected adverse events (SUSARs) were reported for the study.

Dose of CVA21 up to 3 x 10⁸ TCID50 for an additional 9 treatments at 3-week intervals

Dose of CAVATAK up to 3 x 10⁸ TCID50 for an additional 9 treatments at 3-week intervals CVA21

Age, Continuous

Sex: Female, Male

United States

Region of Enrollment

Mark Grose

Safety

Overall Study

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.

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)

Urinary Bladder Neoplasms

Non-Muscle Invasive Bladder Neoplasms

Urologic Neoplasms

Female Urogenital Diseases

Pregnancy Complications

Female Urogenital Diseases and Pregnancy Complications

Urinary Bladder Diseases

Urologic 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

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.

Incidence of Dose-limiting Toxicities Treatment-related Adverse Events.

CAVATAK was administered by intravesical instillation at 1x10\^8 TCID50.

A1 - CVA21 1x10^8 TCID50

CAVATAK was administered at 3x10\^8 TCID50

A2 - CVA21 3x10^8 TCID50.

CAVATAK was administered at 3x10\^8 TCID50 twice.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Pembrolizumab + CVA21 in Advanced NSCLC	NCT02824965	Non-Small Cell ...	Pembrolizumab CVA21	18 Years -	Olivia Newton-John Cancer Research Institute
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
Coxsackie Virus A21 Administered Intravenously (IV) for Solid Tumour Cancers (PSX-X04)	NCT00636558	Melanoma Breast Cancer Prostate Cancer	CVA21	18 Years -	Viralytics
CAVATAK in Patients With Stage IIIc or IV Malignant Melanoma to Extend Dosing to 48 Weeks (VLA-008 CALM Ext)	NCT01636882	Melanoma	CVA21	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
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 cva21

Every month we try and update this database with for cva21 cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Spots Global Cancer Trial Database for cva21

Every month we try and update this database with for cva21 cancer trials from around the world to help patients and their families find trials that might be right for them. We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Every month we try and update this database with for cva21 cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.