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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)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03968419
Recruitment Status : Active, not recruiting
First Posted : May 30, 2019
Last Update Posted : July 6, 2022
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )

Tracking Information
First Submitted Date  ICMJE May 15, 2019
First Posted Date  ICMJE May 30, 2019
Last Update Posted Date July 6, 2022
Actual Study Start Date  ICMJE November 5, 2019
Actual Primary Completion Date April 20, 2022   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: April 22, 2020)
Major Pathological Response (MPR) rate based on Central review [ Time Frame: At time of surgery (approximately 4 - 6 weeks after first dose) ]
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.
Original Primary Outcome Measures  ICMJE
 (submitted: May 29, 2019)
Major Pathological Response (MPR) rate based on Central review [ Time Frame: At time of surgery (approximately 4 - 6 weeks after first dose) ]
This will assess the rate of MPR at the time of surgery in evaluable participants treated with canakinumab alone and in combination with pembrolizumab based on central review.
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: April 22, 2020)
  • 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 ]
    To characterize the prevalence and incidence of immunogenicity (anti-drug antibodies, ADA) of canakinumab
  • 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 ]
    To characterize the prevalence and incidence of immunogenicity (anti-drug antibodies, ADA) of pembrolizumab
  • 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 ]
    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
  • 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 ]
    To characterize the pharmacokinetics of canakinumab therapy
  • 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 ]
    To characterize the pharmacokinetics of pembrolizumab therapy
  • Surgical feasibility rate [ Time Frame: 4 to 6 weeks after first dose ]
    To assess the rate of the surgical feasibility
  • MPR based on central review [ Time Frame: At time of surgery (approximately 4 - 6 weeks after first dose) ]
    This will assess the rate of MPR at the time of surgery in all participants randomized to pembrolizumab monotherapy arm based on central review.
  • MPR based on local review [ Time Frame: At time of surgery (approximately 4 - 6 weeks after first dose) ]
    This will assess the rate of MPR at the time of surgery in all randomized participants based on local review in each treatment arm.
  • Difference in MPR rate based on central review [ Time Frame: At time of surgery (approximately 4 - 6 weeks after first dose) ]
    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.
  • MPR rate based on the levels of biomarkers [ Time Frame: From date of randomization to 130 days after last dose of drug ]
    Biomarkers include PD-L1, CD8, hs-CRP, hs-IL-6
Original Secondary Outcome Measures  ICMJE
 (submitted: May 29, 2019)
  • 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 ]
    To characterize the prevalence and incidence of immunogenicity (anti-drug antibodies, ADA) of canakinumab
  • 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 ]
    To characterize the prevalence and incidence of immunogenicity (anti-drug antibodies, ADA) of pembrolizumab
  • 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 ]
    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
  • 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 ]
    To characterize the pharmacokinetics of canakinumab therapy
  • 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 ]
    To characterize the pharmacokinetics of pembrolizumab therapy
  • Surgical feasibility rate [ Time Frame: 4 to 6 weeks after first dose ]
    To assess the rate of the surgical feasibility
  • MPR based on central review [ Time Frame: At time of surgery (approximately 4 - 6 weeks after first dose) ]
    This will assess the rate of MPR at the time of surgery in evaluable participants in pembrolizumab monotherapy arm based on central review.
  • MPR based on local review [ Time Frame: At time of surgery (approximately 4 - 6 weeks after first dose) ]
    This will assess the rate of MPR at the time of surgery in evaluable participants based on local review in each treatment arm.
  • MPR based on both central & local review [ Time Frame: At time of surgery (approximately 4 - 6 weeks after first dose) ]
    This will assess the rate of MPR at the time of surgery in randomized participants based on both central and local review in each treatment arm.
  • Difference in MPR rate based on central review [ Time Frame: At time of surgery (approximately 4 - 6 weeks after first dose) ]
    This will estimate the difference in MPR and posterior probability of the difference in MPR ≥ 10% between canakinumab + pembrolizumab combination and pembrolizumab alone based on central review.
  • MPR rate based on the levels of biomarkers [ Time Frame: From date of randomization to 130 days after last dose of drug ]
    Biomarkers include PD-L1, CD8, hs-CRP, hs-IL-6
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE 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  ICMJE 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)
Brief Summary 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.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Non-small Cell Lung Cancer
Intervention  ICMJE
  • Drug: canakinumab
    Administered subcutaneously
    Other Name: ACZ885
  • Drug: pembrolizumab
    200mg administered intravenously every 3 weeks
Study Arms  ICMJE
  • Experimental: canakinumab monotherapy
    All patients will receive canakinumab (ACZ885) prior to surgery
    Intervention: Drug: canakinumab
  • Experimental: canakinumab + pembrolizumab
    All patients will receive canakinumab (ACZ885) and pembrolizumab prior to surgery
    Interventions:
    • Drug: canakinumab
    • Drug: pembrolizumab
  • Experimental: pembrolizumab monotherapy
    All patients will receive 2 doses of pembrolizumab prior to surgery
    Intervention: Drug: pembrolizumab
Publications * Garrido P, Pujol JL, Kim ES, Lee JM, Tsuboi M, Gómez-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.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Active, not recruiting
Actual Enrollment  ICMJE
 (submitted: February 24, 2022)
88
Original Estimated Enrollment  ICMJE
 (submitted: May 29, 2019)
110
Estimated Study Completion Date  ICMJE August 18, 2022
Actual Primary Completion Date April 20, 2022   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.

Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Belgium,   Canada,   France,   Germany,   Greece,   Japan,   Netherlands,   Russian Federation,   Spain,   Taiwan,   Turkey,   United States
Removed Location Countries Hungary
 
Administrative Information
NCT Number  ICMJE NCT03968419
Other Study ID Numbers  ICMJE CACZ885V2201C
2018-004813-42 ( EudraCT Number )
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: Yes
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.

Current Responsible Party Novartis ( Novartis Pharmaceuticals )
Original Responsible Party Same as current
Current Study Sponsor  ICMJE Novartis Pharmaceuticals
Original Study Sponsor  ICMJE Same as current
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals
PRS Account Novartis
Verification Date July 2022

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP