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. (CANOPY-N)

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)

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.

Study Overview

• Status: Terminated
• Conditions: Non-small Cell Lung Cancer
• Intervention / Treatment: Drug: Canakinumab; Drug: Pembrolizumab

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).

• Study Type: Interventional
• Enrollment (Actual): 88
• Phase: Phase 2

Contacts and Locations

Study Locations

• Belgium
  • Bruxelles, Belgium, 1000
    • Novartis Investigative Site
• Canada
  • Quebec
    • Montreal, Quebec, Canada, H2W 1T8
      • Novartis Investigative Site
• France
  • Bron, France, 69677
    • Novartis Investigative Site
  • Paris, France, 75679
    • Novartis Investigative Site
  • Herault
    • Montpellier cedex 5, Herault, France, 34059
      • Novartis Investigative Site
• Germany
  • Bad Berka, Germany, 99437
    • Novartis Investigative Site
  • Giessen, Germany, 35392
    • Novartis Investigative Site
  • Halle (Saale), Germany, 06120
    • Novartis Investigative Site
  • Koeln, Germany, 51109
    • Novartis Investigative Site
• Greece
  • Thessaloniki, Greece, 57001
    • Novartis Investigative Site
• Japan
  • Chiba
    • Kashiwa, Chiba, Japan, 277 8577
      • Novartis Investigative Site
• Netherlands
  • Breda, Netherlands, 4819 EV
    • Novartis Investigative Site
  • Hertogenbosch, Netherlands, 5200
    • Novartis Investigative Site
  • Maastricht, Netherlands, 6229 HX
    • Novartis Investigative Site
• Russian Federation
  • Omsk, Russian Federation, 644013
    • Novartis Investigative Site
  • Saint Petersburg, Russian Federation, 197022
    • Novartis Investigative Site
  • St Petersburg, Russian Federation, 195271
    • Novartis Investigative Site
• Spain
  • Madrid, Spain, 28034
    • Novartis Investigative Site
  • Andalucia
    • Jaen, Andalucia, Spain, 23007
      • Novartis Investigative Site
  • Asturias
    • Oviedo, Asturias, Spain, 33011
      • Novartis Investigative Site
• Taiwan
  • Taipei, Taiwan, 110
    • Novartis Investigative Site
  • Taipei, Taiwan, 103616
    • Novartis Investigative Site
• Turkey
  • Izmir, Turkey
    • Novartis Investigative Site
  • Sakarya, Turkey, 54290
    • Novartis Investigative Site
  • Sihhiye / Ankara, Turkey, 06100
    • Novartis Investigative Site
• United States
  • California
    • La Jolla, California, United States, 92037
      • UCLA Oncology Hematology
  • Kansas
    • Kansas City, Kansas, United States, 66160
      • University of Kansas Medical Center Neurology Dept.
  • New York
    • Syracuse, New York, United States, 13210
      • SUNY - Upstate Medical University
  • Texas
    • Houston, Texas, United States, 77030
      • Methodist Hospital / Methodist Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Canakinumab monotherapy; Participants received 200 mg of canakinumab once every 3 weeks for a maximum duration of 6 weeks prior to surgery	Drug: Canakinumab; 200 mg of canakinumab administered via subcutaneous injections once every 3 weeks for a maximum duration of 6 weeks; Other Names: ACZ885
Experimental: Canakinumab + pembrolizumab; 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	Drug: Canakinumab; 200 mg of canakinumab administered via subcutaneous injections once every 3 weeks for a maximum duration of 6 weeks; Other Names: ACZ885; Drug: Pembrolizumab; 200 mg of pembrolizumab administered via infusion once every 3 weeks for a maximum duration of 6 weeks
Experimental: Pembrolizumab monotherapy; Participants received 200 mg of pembrolizumab every 3 weeks for a maximum duration of 6 weeks prior to surgery	Drug: Pembrolizumab; 200 mg of pembrolizumab administered via infusion once every 3 weeks for a maximum duration of 6 weeks

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	At time of surgery (up to 6 weeks after first dose of study treatment)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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	Predose (0 hour) on Day 1 of Cycle 1 (Cycle=21 days)
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)	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
Pembrolizumab ADA Prevalence	Pembrolizumab ADA prevalence at baseline was calculated as the percentage of participants who had a pembrolizumab ADA positive result at baseline	Predose (0 hour) on Day 1 of Cycle 1 (Cycle = 21 days)
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)	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
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	From date of randomization to date of surgery, assessed up to 6 weeks
Serum Canakinumab Concentration	Canakinumab serum concentrations were determined at the specified time points.	Predose (0 hour) on Day 1 of Cycles 1 and 2 (Cycle =21 days)
Serum Pembrolizumab Concentration	Pembrolizumab serum concentrations were determined at the specified time points.	Predose (0 hour) and 0.5 hours post dose on Day 1 of Cycle 1 and predose on Cycle 2 (Cycle =21 days)
Surgical Feasibility Rate	Surgical feasibility rate was defined as the percentage of subjects who underwent surgery following study treatment.	Up to 6 weeks after first dose
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.	At time of surgery (up to 6 weeks after first dose)
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.	At time of surgery (up to 6 weeks after first dose of study treatment)
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.	At time of surgery (up to 6 weeks after first dose)
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.	From date of randomization up to 6 weeks after first dose

Collaborators and Investigators

• Sponsor: Novartis Pharmaceuticals
• Investigators: Study Director: Novartis Pharmaceuticals, Novartis Pharmaceuticals

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start (Actual): November 5, 2019
• Primary Completion (Actual): April 20, 2022
• Study Completion (Actual): August 15, 2022

Study Registration Dates

• First Submitted: May 15, 2019
• First Submitted That Met QC Criteria: May 29, 2019
• First Posted (Actual): May 30, 2019

Study Record Updates

• Last Update Posted (Actual): July 3, 2023
• Last Update Submitted That Met QC Criteria: June 12, 2023
• Last Verified: June 1, 2023

More Information

Terms related to this study

• Keywords: NSCLC; CD8; non-small cell lung cancer; surgery; PD-L1; pembrolizumab; neo-adjuvant; non small cell lung cancer; hsCRP; ACZ885; canakinumab; hs-CRP; squamous; neo adjuvant; early stage NSCLC; non-squamous,; MPR; major pathological response; hs-IL-6; CANOPY
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Neoplasms; Lung Diseases; Neoplasms by Site; Respiratory Tract Neoplasms; Thoracic Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Carcinoma, Non-Small-Cell Lung; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Antineoplastic Agents, Immunological; Immune Checkpoint Inhibitors; Pembrolizumab
• Other Study ID Numbers: CACZ885V2201C; 2018-004813-42 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

IPD 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.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No