Description:
Major pathological response (MPR) rate of canakinumab given as a neoadjuvant treatment,
either as single agent or in combination with pembrolizumab, in addition to evaluate the MPR
rate of pembrolizumab as a single agent. Additionally the dynamics of the tumor
microenvironment changes on treatment by comparing pre-, on- and post-treatment samples will
be evaluated.
Title
- Brief Title: This Study Will Evaluate the Effect of Canakinumab or Pembrolizumab Given as Monotherapy or in Combination as Neo-adjuvant Treatment for Subjects With Early Stages NSCLC.
- Official Title: A Randomized, Open-label, Phase II Study of Canakinumab or Pembrolizumab as Monotherapy or in Combination as Neoadjuvant Therapy in Subjects With Resectable Non-small Cell Lung Cancer (CANOPY-N)
Clinical Trial IDs
- ORG STUDY ID:
CACZ885V2201C
- SECONDARY ID:
2018-004813-42
- NCT ID:
NCT03968419
Conditions
- Non-small Cell Lung Cancer
Interventions
Drug | Synonyms | Arms |
---|
canakinumab | ACZ885 | canakinumab + pembrolizumab |
pembrolizumab | | canakinumab + pembrolizumab |
Purpose
Major pathological response (MPR) rate of canakinumab given as a neoadjuvant treatment,
either as single agent or in combination with pembrolizumab, in addition to evaluate the MPR
rate of pembrolizumab as a single agent. Additionally the dynamics of the tumor
microenvironment changes on treatment by comparing pre-, on- and post-treatment samples will
be evaluated.
Trial Arms
Name | Type | Description | Interventions |
---|
canakinumab monotherapy | Experimental | All patients will receive canakinumab (ACZ885) prior to surgery | |
canakinumab + pembrolizumab | Experimental | All patients will receive canakinumab (ACZ885) and pembrolizumab prior to surgery | |
pembrolizumab monotherapy | Experimental | All patients will receive 2 doses of pembrolizumab prior to surgery | |
Eligibility Criteria
Key inclusion criteria:
- Histologically confirmed NSCLC stage IB-IIIA (per AJCC 8th edition), deemed suitable
for primary resection by treating surgeon, except for N2 and T4 tumors.
- Subject must be eligible for surgery and with a planned surgical resection in
approximately 4-6 weeks (after the first dose of study treatment).
- A mandatory newly obtained tissue biopsy from primary site is required for study
enrollment. An archival biopsy is also acceptable if obtained up to 5 months before
first day of study treatment and if the subject did not go through antineoplastic
systemic therapies between biopsy collection date and beginning of study treatment.
Note: Aspirates will not be accepted.
- Eastern Cooperative oncology group (ECOG) performance status of 0 or 1.
Key exclusion criteria:
- Subjects with unresectable or metastatic disease.
- History of severe hypersensitivity reactions to monoclonal antibodies, which in the
opinion of the investigator may pose an increased risk of serious infusion reaction
- Subjects who received prior systemic therapy (including chemotherapy, other
anti-cancer therapies and any other antibody or drug specifically targeting T-cell
co-stimulation or immune checkpoint pathways) in the past 3 years before screening
- Active autoimmune disease that has required systemic treatment in the past 2 years
prior to randomization. Control of the disorder with replacement therapy is permitted
- Subject with suspected or proven immunocompromised state or infections
Other protocol-defined inclusion/exclusion criteria may apply.
Maximum Eligible Age: | N/A |
Minimum Eligible Age: | 18 Years |
Eligible Gender: | All |
Healthy Volunteers: | No |
Primary Outcome Measures
Measure: | Major Pathological Response (MPR) rate based on Central review |
Time Frame: | At time of surgery (approximately 4 - 6 weeks after first dose) |
Safety Issue: | |
Description: | This will assess the rate of MPR at the time of surgery in all participants randomized to canakinumab alone and in combination with pembrolizumab arms based on central review. |
Secondary Outcome Measures
Measure: | Antidrug antibodies (ADA) of canakinumab |
Time Frame: | Predose (0 hour) on Day 1 of Cycles 1 and 2 (Cycle length =21 days), at end of treatment & then at 26, 78 and 130 days after last dose |
Safety Issue: | |
Description: | To characterize the prevalence and incidence of immunogenicity (anti-drug antibodies, ADA) of canakinumab |
Measure: | Antidrug antibodies (ADA) of pembrolizumab |
Time Frame: | Predose (0 hour) on Day 1 of Cycles 1 and 2 (Cycle length =21 days), at end of treatment and then at 26 days after last dose |
Safety Issue: | |
Description: | To characterize the prevalence and incidence of immunogenicity (anti-drug antibodies, ADA) of pembrolizumab |
Measure: | Overall response rate (ORR) per investigator assessment using RECIST v1.1 |
Time Frame: | From date of randomization to date of surgery up to 6 weeks |
Safety Issue: | |
Description: | ORR is defined as the proportion of subjects with confirmed best overall response of complete response (CR) or partial response (PR), as per investigator's assessment by RECIST 1.1 |
Measure: | Serum canakinumab concentration |
Time Frame: | Predose (0 hour) on Day 1 of Cycles 1 and 2 (Cycle length =21 days), at end of treatment & then at 26, 78 and 130 days after last dose |
Safety Issue: | |
Description: | To characterize the pharmacokinetics of canakinumab therapy |
Measure: | Serum pembrolizumab concentration |
Time Frame: | Predose (0 hour) on Day 1 of Cycles 1 and 2 (Cycle length =21 days), end of infusion on Day 1 Cycle 1, at end of treatment and then at 26 days after last dose |
Safety Issue: | |
Description: | To characterize the pharmacokinetics of pembrolizumab therapy |
Measure: | Surgical feasibility rate |
Time Frame: | 4 to 6 weeks after first dose |
Safety Issue: | |
Description: | To assess the rate of the surgical feasibility |
Measure: | MPR based on central review |
Time Frame: | At time of surgery (approximately 4 - 6 weeks after first dose) |
Safety Issue: | |
Description: | This will assess the rate of MPR at the time of surgery in all participants randomized to pembrolizumab monotherapy arm based on central review. |
Measure: | MPR based on local review |
Time Frame: | At time of surgery (approximately 4 - 6 weeks after first dose) |
Safety Issue: | |
Description: | This will assess the rate of MPR at the time of surgery in all randomized participants based on local review in each treatment arm. |
Measure: | Difference in MPR rate based on central review |
Time Frame: | At time of surgery (approximately 4 - 6 weeks after first dose) |
Safety Issue: | |
Description: | This will estimate the difference in MPR and posterior probability of the difference in MPR ≥ 10% between participants randomized to canakinumab + pembrolizumab combination and pembrolizumab alone based on central review. |
Measure: | MPR rate based on the levels of biomarkers |
Time Frame: | From date of randomization to 130 days after last dose of drug |
Safety Issue: | |
Description: | Biomarkers include PD-L1, CD8, hs-CRP, hs-IL-6 |
Details
Phase: | Phase 2 |
Primary Purpose: | Interventional |
Overall Status: | Recruiting |
Lead Sponsor: | Novartis Pharmaceuticals |
Trial Keywords
- ACZ885
- canakinumab
- pembrolizumab
- NSCLC
- non-small cell lung cancer
- non small cell lung cancer
- early stage NSCLC
- squamous
- non-squamous,
- MPR
- major pathological response
- hs-CRP
- PD-L1
- hsCRP
- surgery
- neo-adjuvant
- neo adjuvant
- CD8
- hs-IL-6
- CANOPY
Last Updated
May 27, 2021