Clinical trial NCT02043665: CVA21 and Pembrolizumab in NSCLC & Bladder Cancer (VLA-009 STORM/ KEYNOTE-200)
Official title: A Phase 1, Dose-finding and Signal-seeking Study of the Safety & Efficacy of Intravenous CAVATAK® Alone and in Combination With Pembrolizumab in Patients With Late Stage Solid Tumours (VLA-009 STORM / KEYNOTE-200)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Non-small Cell Lung Cancer
Bladder Cancer
Keywords: CAVATAK
KEYNOTE-200
pembrolizumab
lung cancer
bladder cancer
Lead sponsor: Viralytics
Sponsor class: INDUSTRY
Collaborators: name: Merck Sharp & Dohme LLC
First posted: 2014-01-23
Enrollment: 85
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: The purpose of this trial is to assess the ability of CVA21, either alone (Part A) or in combination with pembrolizumab (Part B), to reach and to replicate in existing tumors (while sparing normal cells) and to establish a safe multi-dose schedule of the virus for the treatment of solid tumors where enhanced expression of ICAM-1 and/ or DAF receptor occurs.

This trial consists of 2 sequential parts: VLA-009 (Part A) conducted only in the UK and employed CVA21 as a monotherapy in NSCLC, castrate-resistant prostate cancer, melanoma and bladder cancer. VLA-009 (Part B) conducted in the US, AUS and UK employs CVA21 with pembrolizumab in NSCLC and bladder cancer.

Both VLA-009A and VLA-009B are open-label, multi-center, ascending dose escalation (3+3 design) dose-finding and signal-seeking studies.

Part A of the study is now complete and closed to enrolment. Part B is currently enrolling.


Eligibility criteria: Inclusion Criteria:

* Histologically-confirmed (1) NSCLC, (2) bladder cancer, (3) castrate-resistant prostate cancer which are metastatic, or (4) stage 3C or stage 4 melanoma.
* VLA009A: Locally advanced and/or metastatic disease for which curative surgery and/or radiation therapy is not possible and judged not to be a candidate for the current standard of care treatment. VLA009B: locally advanced and/or metastatic disease and judged to be a candidate for pembrolizumab to be used in combination with CVA21.
* All subjects in Cohort 3 or Phase 2 dose (P2D) must have a lesion accessible for FNA or core or open biopsy on day 8 of the first treatment cycle.
* No CVA21 neutralising antibody (≤ 1:16)
* Measurable or evaluable disease

Exclusion Criteria:

* Second primary malignancy within the past 2 years (except non-melanoma skin cancer, in situ carcinoma of the cervix, breast cancer)
* Concurrent immunosuppressive therapy and no known immunosuppressive disease other than primary tumour

Primary outcomes:
measure: Response rate assessed according to immune-related RECIST 1.1 criteria
timeFrame: Up to 6 months
Secondary outcomes:
Other outcomes:
Locations:
city: Santa Monica
country: United States
facility: John Wayne Cancer Institute
state: California
city: Coral Gables
country: United States
facility: University of Miami
state: Florida
city: Niles
country: United States
facility: Advocate Health
state: Illinois
city: Detroit
country: United States
facility: Karmanos Cancer Institute
state: Michigan
city: New York
country: United States
facility: Memorial Sloan Kettering Cancer Center
state: New York
city: Portland
country: United States
facility: Providence Portland Medical Center
state: Oregon
city: Philadelphia
country: United States
facility: Fox Chase Cancer Center
state: Pennsylvania
city: Dallas
country: United States
facility: UT Southwestern
state: Texas
city: Salt Lake City
country: United States
facility: Huntsman Cancer Institute
state: Utah
city: Southport
country: Australia
facility: Tasman Oncology Research
state: Queensland
city: Clayton
country: Australia
facility: Monash Health
state: Victoria
city: Fitzroy
country: Australia
facility: St Vincent's Hospital, Melbourne
state: Victoria
city: Geelong
country: Australia
facility: Barwon Health
state: Victoria
city: Richmond
country: Australia
facility: Epworth HealthCare
state: Victoria
city: Subiaco
country: Australia
facility: St John of God Healthcare
state: Western Australia
city: Chelsea
country: United Kingdom
facility: Royal Marsden NHS Foundation Trust
city: Guildford
country: United Kingdom
facility: Royal Surrey County Hospital
city: Leeds
country: United Kingdom
facility: St. James University Hospital
Study officials:
affiliation: Royal Surrey County Hospital NHS Foundation Trust
name: Hardev Pandha, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Rudin CM, Pandha HS, Zibelman M, Akerley WL, Harrington KJ, Day D, Hill AG, O'Day SJ, Clay TD, Wright GM, Jennens RR, Gerber DE, Rosenberg JE, Ralph C, Campbell DC, Curti BD, Merchan JR, Ren Y, Schmidt EV, Guttman L, Gupta S. Phase 1, open-label, dose-escalation study on the safety, pharmacokinetics, and preliminary efficacy of intravenous Coxsackievirus A21 (V937), with or without pembrolizumab, in patients with advanced solid tumors. J Immunother Cancer. 2023 Jan;11(1):e005007. doi: 10.1136/jitc-2022-005007.