Pembrolizumab + CVA21 in Advanced NSCLC
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|ClinicalTrials.gov Identifier: NCT02824965|
Recruitment Status : Active, not recruiting
First Posted : July 7, 2016
Last Update Posted : February 12, 2020
|Condition or disease||Intervention/treatment||Phase|
|Non-Small Cell Lung Cancer||Drug: Pembrolizumab Biological: CVA21||Phase 1|
Primary Objective & Hypothesis
To evaluate the safety of intravenous CVA21 in combination with pembrolizumab in patients with advanced NSCLC.
Pembrolizumab in combination with intravenous CVA21 will be well tolerated in patients with advanced NSCLC.
Secondary Objective & Hypothesis
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.
i. CVA21 will induce immune cell infiltration into tumors of patients that lack an immune cell rich micro-environment.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||11 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||A Phase I/II Open-label Trial of Intravenous CAVATAK^TM in Combination With Pembrolizumab for the Treatment of Patients With Advanced NSCLC|
|Actual Study Start Date :||August 9, 2017|
|Estimated Primary Completion Date :||December 2020|
|Estimated Study Completion Date :||December 2020|
Experimental: Pembrolizumab+1x10^9 TCID50 CVA21
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.
Other Name: KEYTRUDA
CAVATAK is an oncolytic Coxsackie virus that specifically infects and kills ICAM overexpressing tumour cells
Other Name: CAVATAK, Coxsackie virus 21
- Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability]. [ Time Frame: 0-24 months ]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.
- ORR from the date of first study treatment as assessed by RECIST [ Time Frame: 0-24 months ]Quantification of the Objective Response rate in patients on study by RECIST
- ORR from the date of first study treatment as assessed by immune related response criteria (irRC) [ Time Frame: 0-24 Months ]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).
- PFS [ Time Frame: 0-36 Months ]Progression Free survival from first study treatment until end of study
- Incidence of detectable CVA21 virus and neutralizing antibodies [ Time Frame: 0-24 Months ]Measurement of CVA21 virus and neutralizing antibodies at each CVA21 injection time point
- OS [ Time Frame: 0-36 Months ]Overall survival of patients on study from first study treatment.
- Change in PD-L1 expression from sequential biopsies in NSCLC patients [ Time Frame: 0-36 months ]PD-L1 expression will be measured using IHC from baseline and sequential biopsies
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02824965
|Heidelberg, Victoria, Australia, 3078|
|Principal Investigator:||Thomas John||Austin Health|