Back to resultsThis 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. (CANOPY-N)
Primary Purpose
Non-small Cell Lung Cancer
Status
Terminated
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
Canakinumab
Pembrolizumab
Sponsored by
About this trial
This is an interventional treatment trial for Non-small Cell Lung Cancer focused on measuring 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
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.
Sites / Locations
- UCLA Oncology Hematology
- University of Kansas Medical Center Neurology Dept.
- SUNY - Upstate Medical University
- Methodist Hospital / Methodist Cancer Center
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm Type
Experimental
Experimental
Experimental
Arm Label
Canakinumab monotherapy
Canakinumab + pembrolizumab
Pembrolizumab monotherapy
Arm Description
Participants received 200 mg of canakinumab once every 3 weeks for a maximum duration of 6 weeks prior to surgery
Participants received 200 mg of canakinumab in combination with 200 mg of pembrolizumab once every 3 weeks for a maximum duration of 6 weeks prior to surgery
Participants received 200 mg of pembrolizumab every 3 weeks for a maximum duration of 6 weeks prior to surgery
Outcomes
Primary Outcome Measures
Major Pathological Response (MPR) Rate at the Time of Surgery in Subjects Randomized to Canakinumab Monotherapy and in Combination With Pembrolizumab Based on Central Review
MPR was defined as the percentage of participants with major pathological response (defined as ≤10% residual viable tumor cells on surgical samples). Any participant who had >10% residual viable cancer cells, or started new antineoplastic therapy prior to surgery, or did not have the surgery performed, or had the surgery performed but with unevaluable MPR result, was considered as a non-responder.
MPR was assessed at the time of surgery in all subjects randomized to canakinumab monotherapy and in combination with pembrolizumab based on central review.
Secondary Outcome Measures
Canakinumab Antidrug Antibodies (ADA) Prevalence
Canakinumab ADA prevalence at baseline was calculated as the percentage of participants who had a canakinumab ADA positive result at baseline
Canakinumab ADA Incidence
Canakinumab ADA incidence on treatment was calculated as the percentage of participants who were canakinumab treatment-induced ADA positive (post-baseline ADA positive with ADA-negative sample at baseline) and canakinumab treatment-boosted ADA positive (post-baseline ADA positive with titer that is at least the fold titer change greater than the ADA-positive baseline titer)
Pembrolizumab ADA Prevalence
Pembrolizumab ADA prevalence at baseline was calculated as the percentage of participants who had a pembrolizumab ADA positive result at baseline
Pembrolizumab ADA Incidence
Pembrolizumab ADA incidence on treatment was calculated as the percentage of participants who were pembrolizumab treatment-induced ADA positive (post-baseline ADA positive with ADA-negative sample at baseline) and pembrolizumab treatment-boosted ADA positive (post-baseline ADA positive with titer that is at least the fold titer change greater than the ADA-positive baseline titer)
Overall Response Rate (ORR) Based on Local Investigator Assessment Using RECIST v1.1
ORR is defined as the percentage of subjects with confirmed best overall response of complete response (CR) or partial response (PR), as per local investigator's assessment by RECIST 1.1.
CR: Disappearance of all non-nodal target lesions. In addition, any pathological lymph nodes assigned as target lesions must have a reduction in short axis to < 10 mm.
PR: At least a 30% decrease in the sum of diameter of all target lesions, taking as reference the baseline sum of diameters
Serum Canakinumab Concentration
Canakinumab serum concentrations were determined at the specified time points.
Serum Pembrolizumab Concentration
Pembrolizumab serum concentrations were determined at the specified time points.
Surgical Feasibility Rate
Surgical feasibility rate was defined as the percentage of subjects who underwent surgery following study treatment.
Major Pathological Response (MPR) Rate at the Time of Surgery in Subjects Randomized to Pembrolizumab Monotherapy Based on Central Review
MPR was defined as the percentage of participants with major pathological response (defined as ≤10% residual viable tumor cells on surgical samples). Any participant who had >10% residual viable cancer cells, or started new antineoplastic therapy prior to surgery, or did not have the surgery performed, or had the surgery performed but with unevaluable MPR result, was considered as a non-responder.
MPR was assessed at the time of surgery in all subjects randomized to pembrolizumab monotherapy arm based on central review.
Difference in Major Pathological Response (MPR) Rate Between the Canakinumab Plus Pembrolizumab Arm and the Pembrolizumab Arm Based on Central Review
MPR was defined as the percentage of participants with ≤10% residual viable tumor cells on surgical samples. MPR was assessed at the time of surgery based on central review. The difference in MPR rate between the canakinumab plus pembrolizumab arm and the pembrolizumab arm based on central review along with the Chang and Zhang confidence interval was assessed.
Major Pathological Response (MPR) Rate at the Time of Surgery in All Subjects Based on Local Review
MPR was defined as the percentage of participants with major pathological response (defined as ≤10% residual viable tumor cells on surgical samples). Any participant who had >10% residual viable cancer cells, or started new antineoplastic therapy prior to surgery, or did not have the surgery performed, or had the surgery performed but with unevaluable MPR result, was considered as a non-responder.
MPR was assessed at the time of surgery in all subjects based on local review.
Major Pathological Response (MPR) Rate Based on the Levels of Biomarkers
MPR was defined as the percentage of participants with major pathological response (defined as ≤10% residual viable tumor cells on surgical samples). Any participant who had >10% residual viable cancer cells, or started new antineoplastic therapy prior to surgery, or did not have the surgery performed, or had the surgery performed but with unevaluable MPR result, was considered as a non-responder.
MPR rate was analyzed by the biomarker subgroups at baseline. Biomarkers included PD-L1, CD8, hs-CRP and hs-IL-6.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT03968419
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.
Acronym
CANOPY-N
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)
Study Type
Interventional
2. Study Status
Record Verification Date
June 2023
Overall Recruitment Status
Terminated
Why Stopped
Study early terminated due to low enrollment compared to the anticipated figures.
Study Start Date
November 5, 2019 (Actual)
Primary Completion Date
April 20, 2022 (Actual)
Study Completion Date
August 15, 2022 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Novartis Pharmaceuticals
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
Brief Summary
The purpose of this study was to evaluate the 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 of pembrolizumab as a single agent and the dynamic of the tumor microenvironment changes on treatment.
Detailed Description
This was a randomized, phase II, open-label study evaluating canakinumab, an anti-IL-1β monoclonal antibody, or pembrolizumab, a monoclonal antibody designed to block the PD-1 receptor, as monotherapy or in combination as neoadjuvant therapy. The study population included adult subjects with resectable non-small cell lung cancer (NSCLC) planned for surgery in approximately 4-6 weeks. Subjects were treated for a maximum duration of 6 weeks (2 cycles) until surgery, progression, unacceptable toxicity or discontinuation from the study treatment for any other reason.
Subjects were randomized in a 2:2:1 ratio to one of the 3 treatment arms (canakinumab alone or canakinumab in combination with pembrolizumab or pembrolizumab alone). Surgery was performed between 4 to 6 weeks after the first dose of study treatment.
All randomized subjects were followed for safety for up to 130 days following the last dose of study treatment (safety follow-up period).
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Non-small Cell Lung Cancer
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
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
88 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Canakinumab monotherapy
Arm Type
Experimental
Arm Description
Participants received 200 mg of canakinumab once every 3 weeks for a maximum duration of 6 weeks prior to surgery
Arm Title
Canakinumab + pembrolizumab
Arm Type
Experimental
Arm Description
Participants received 200 mg of canakinumab in combination with 200 mg of pembrolizumab once every 3 weeks for a maximum duration of 6 weeks prior to surgery
Arm Title
Pembrolizumab monotherapy
Arm Type
Experimental
Arm Description
Participants received 200 mg of pembrolizumab every 3 weeks for a maximum duration of 6 weeks prior to surgery
Intervention Type
Drug
Intervention Name(s)
Canakinumab
Other Intervention Name(s)
ACZ885
Intervention Description
200 mg of canakinumab administered via subcutaneous injections once every 3 weeks for a maximum duration of 6 weeks
Intervention Type
Drug
Intervention Name(s)
Pembrolizumab
Intervention Description
200 mg of pembrolizumab administered via infusion once every 3 weeks for a maximum duration of 6 weeks
Primary Outcome Measure Information:
Title
Major Pathological Response (MPR) Rate at the Time of Surgery in Subjects Randomized to Canakinumab Monotherapy and in Combination With Pembrolizumab Based on Central Review
Description
MPR was defined as the percentage of participants with major pathological response (defined as ≤10% residual viable tumor cells on surgical samples). Any participant who had >10% residual viable cancer cells, or started new antineoplastic therapy prior to surgery, or did not have the surgery performed, or had the surgery performed but with unevaluable MPR result, was considered as a non-responder.
MPR was assessed at the time of surgery in all subjects randomized to canakinumab monotherapy and in combination with pembrolizumab based on central review.
Time Frame
At time of surgery (up to 6 weeks after first dose of study treatment)
Secondary Outcome Measure Information:
Title
Canakinumab Antidrug Antibodies (ADA) Prevalence
Description
Canakinumab ADA prevalence at baseline was calculated as the percentage of participants who had a canakinumab ADA positive result at baseline
Time Frame
Predose (0 hour) on Day 1 of Cycle 1 (Cycle=21 days)
Title
Canakinumab ADA Incidence
Description
Canakinumab ADA incidence on treatment was calculated as the percentage of participants who were canakinumab treatment-induced ADA positive (post-baseline ADA positive with ADA-negative sample at baseline) and canakinumab treatment-boosted ADA positive (post-baseline ADA positive with titer that is at least the fold titer change greater than the ADA-positive baseline titer)
Time Frame
From baseline (Predose on Day 1 of Cycle 1) up to 130 days after last dose of study treatment (assessed up to 24.6 weeks). Cycle = 21 days
Title
Pembrolizumab ADA Prevalence
Description
Pembrolizumab ADA prevalence at baseline was calculated as the percentage of participants who had a pembrolizumab ADA positive result at baseline
Time Frame
Predose (0 hour) on Day 1 of Cycle 1 (Cycle = 21 days)
Title
Pembrolizumab ADA Incidence
Description
Pembrolizumab ADA incidence on treatment was calculated as the percentage of participants who were pembrolizumab treatment-induced ADA positive (post-baseline ADA positive with ADA-negative sample at baseline) and pembrolizumab treatment-boosted ADA positive (post-baseline ADA positive with titer that is at least the fold titer change greater than the ADA-positive baseline titer)
Time Frame
From baseline (Predose on Day 1 of Cycle 1) up to 26 days after last dose of study treatment (assessed up to 10.7 weeks). Cycle = 21 days
Title
Overall Response Rate (ORR) Based on Local Investigator Assessment Using RECIST v1.1
Description
ORR is defined as the percentage of subjects with confirmed best overall response of complete response (CR) or partial response (PR), as per local investigator's assessment by RECIST 1.1.
CR: Disappearance of all non-nodal target lesions. In addition, any pathological lymph nodes assigned as target lesions must have a reduction in short axis to < 10 mm.
PR: At least a 30% decrease in the sum of diameter of all target lesions, taking as reference the baseline sum of diameters
Time Frame
From date of randomization to date of surgery, assessed up to 6 weeks
Title
Serum Canakinumab Concentration
Description
Canakinumab serum concentrations were determined at the specified time points.
Time Frame
Predose (0 hour) on Day 1 of Cycles 1 and 2 (Cycle =21 days)
Title
Serum Pembrolizumab Concentration
Description
Pembrolizumab serum concentrations were determined at the specified time points.
Time Frame
Predose (0 hour) and 0.5 hours post dose on Day 1 of Cycle 1 and predose on Cycle 2 (Cycle =21 days)
Title
Surgical Feasibility Rate
Description
Surgical feasibility rate was defined as the percentage of subjects who underwent surgery following study treatment.
Time Frame
Up to 6 weeks after first dose
Title
Major Pathological Response (MPR) Rate at the Time of Surgery in Subjects Randomized to Pembrolizumab Monotherapy Based on Central Review
Description
MPR was defined as the percentage of participants with major pathological response (defined as ≤10% residual viable tumor cells on surgical samples). Any participant who had >10% residual viable cancer cells, or started new antineoplastic therapy prior to surgery, or did not have the surgery performed, or had the surgery performed but with unevaluable MPR result, was considered as a non-responder.
MPR was assessed at the time of surgery in all subjects randomized to pembrolizumab monotherapy arm based on central review.
Time Frame
At time of surgery (up to 6 weeks after first dose)
Title
Difference in Major Pathological Response (MPR) Rate Between the Canakinumab Plus Pembrolizumab Arm and the Pembrolizumab Arm Based on Central Review
Description
MPR was defined as the percentage of participants with ≤10% residual viable tumor cells on surgical samples. MPR was assessed at the time of surgery based on central review. The difference in MPR rate between the canakinumab plus pembrolizumab arm and the pembrolizumab arm based on central review along with the Chang and Zhang confidence interval was assessed.
Time Frame
At time of surgery (up to 6 weeks after first dose of study treatment)
Title
Major Pathological Response (MPR) Rate at the Time of Surgery in All Subjects Based on Local Review
Description
MPR was defined as the percentage of participants with major pathological response (defined as ≤10% residual viable tumor cells on surgical samples). Any participant who had >10% residual viable cancer cells, or started new antineoplastic therapy prior to surgery, or did not have the surgery performed, or had the surgery performed but with unevaluable MPR result, was considered as a non-responder.
MPR was assessed at the time of surgery in all subjects based on local review.
Time Frame
At time of surgery (up to 6 weeks after first dose)
Title
Major Pathological Response (MPR) Rate Based on the Levels of Biomarkers
Description
MPR was defined as the percentage of participants with major pathological response (defined as ≤10% residual viable tumor cells on surgical samples). Any participant who had >10% residual viable cancer cells, or started new antineoplastic therapy prior to surgery, or did not have the surgery performed, or had the surgery performed but with unevaluable MPR result, was considered as a non-responder.
MPR rate was analyzed by the biomarker subgroups at baseline. Biomarkers included PD-L1, CD8, hs-CRP and hs-IL-6.
Time Frame
From date of randomization up to 6 weeks after first dose
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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 have been 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 was required for study enrollment. An archival biopsy was 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.
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 was permitted
Subject with suspected or proven immunocompromised state or infections
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Novartis Pharmaceuticals
Organizational Affiliation
Novartis Pharmaceuticals
Official's Role
Study Director
Facility Information:
Facility Name
UCLA Oncology Hematology
City
La Jolla
State/Province
California
ZIP/Postal Code
92037
Country
United States
Facility Name
University of Kansas Medical Center Neurology Dept.
City
Kansas City
State/Province
Kansas
ZIP/Postal Code
66160
Country
United States
Facility Name
SUNY - Upstate Medical University
City
Syracuse
State/Province
New York
ZIP/Postal Code
13210
Country
United States
Facility Name
Methodist Hospital / Methodist Cancer Center
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States
Facility Name
Novartis Investigative Site
City
Bruxelles
ZIP/Postal Code
1000
Country
Belgium
Facility Name
Novartis Investigative Site
City
Montreal
State/Province
Quebec
ZIP/Postal Code
H2W 1T8
Country
Canada
Facility Name
Novartis Investigative Site
City
Montpellier cedex 5
State/Province
Herault
ZIP/Postal Code
34059
Country
France
Facility Name
Novartis Investigative Site
City
Bron
ZIP/Postal Code
69677
Country
France
Facility Name
Novartis Investigative Site
City
Paris
ZIP/Postal Code
75679
Country
France
Facility Name
Novartis Investigative Site
City
Bad Berka
ZIP/Postal Code
99437
Country
Germany
Facility Name
Novartis Investigative Site
City
Giessen
ZIP/Postal Code
35392
Country
Germany
Facility Name
Novartis Investigative Site
City
Halle (Saale)
ZIP/Postal Code
06120
Country
Germany
Facility Name
Novartis Investigative Site
City
Koeln
ZIP/Postal Code
51109
Country
Germany
Facility Name
Novartis Investigative Site
City
Thessaloniki
ZIP/Postal Code
57001
Country
Greece
Facility Name
Novartis Investigative Site
City
Kashiwa
State/Province
Chiba
ZIP/Postal Code
277 8577
Country
Japan
Facility Name
Novartis Investigative Site
City
Breda
ZIP/Postal Code
4819 EV
Country
Netherlands
Facility Name
Novartis Investigative Site
City
Hertogenbosch
ZIP/Postal Code
5200
Country
Netherlands
Facility Name
Novartis Investigative Site
City
Maastricht
ZIP/Postal Code
6229 HX
Country
Netherlands
Facility Name
Novartis Investigative Site
City
Omsk
ZIP/Postal Code
644013
Country
Russian Federation
Facility Name
Novartis Investigative Site
City
Saint Petersburg
ZIP/Postal Code
197022
Country
Russian Federation
Facility Name
Novartis Investigative Site
City
St Petersburg
ZIP/Postal Code
195271
Country
Russian Federation
Facility Name
Novartis Investigative Site
City
Jaen
State/Province
Andalucia
ZIP/Postal Code
23007
Country
Spain
Facility Name
Novartis Investigative Site
City
Oviedo
State/Province
Asturias
ZIP/Postal Code
33011
Country
Spain
Facility Name
Novartis Investigative Site
City
Madrid
ZIP/Postal Code
28034
Country
Spain
Facility Name
Novartis Investigative Site
City
Taipei
ZIP/Postal Code
103616
Country
Taiwan
Facility Name
Novartis Investigative Site
City
Taipei
ZIP/Postal Code
110
Country
Taiwan
Facility Name
Novartis Investigative Site
City
Izmir
Country
Turkey
Facility Name
Novartis Investigative Site
City
Sakarya
ZIP/Postal Code
54290
Country
Turkey
Facility Name
Novartis Investigative Site
City
Sihhiye / Ankara
ZIP/Postal Code
06100
Country
Turkey
12. IPD Sharing Statement
Plan to Share IPD
Yes
IPD Sharing Plan Description
Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent expert panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations.
This trial data is currently available according to the process described on www.clinicalstudydatarequest.com.
Citations:
PubMed Identifier
33648347
Citation
Garrido P, Pujol JL, Kim ES, Lee JM, Tsuboi M, Gomez-Rueda A, Benito A, Moreno N, Gorospe L, Dong T, Blin C, Rodrik-Outmezguine V, Passos VQ, Mok TS. Canakinumab with and without pembrolizumab in patients with resectable non-small-cell lung cancer: CANOPY-N study design. Future Oncol. 2021 Apr;17(12):1459-1472. doi: 10.2217/fon-2020-1098. Epub 2021 Mar 2.
Results Reference
derived
Learn more about this trial
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.
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