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Study of Efficacy and Safety of Pembrolizumab Plus Platinum-based Doublet Chemotherapy With or Without Canakinumab in Previously Untreated Locally Advanced or Metastatic Non-squamous and Squamous NSCLC Subjects (CANOPY-1)

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ClinicalTrials.gov Identifier: NCT03631199
Recruitment Status : Active, not recruiting
First Posted : August 15, 2018
Last Update Posted : September 13, 2021
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )

Tracking Information
First Submitted Date  ICMJE August 6, 2018
First Posted Date  ICMJE August 15, 2018
Last Update Posted Date September 13, 2021
Actual Study Start Date  ICMJE December 21, 2018
Actual Primary Completion Date August 9, 2021   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: November 7, 2018)
  • Safety run-in part: Incidence of dose limiting toxicities (DLTs) [ Time Frame: 6 months from start of safety run-in part ]
    Incidence of DLTs assessed among at least 6 evaluable subjects during the first 42 days of study treatment
  • Double-blind, randomized, placebo-controlled part: Progression free survival (PFS) per investigator assessment using RECIST v1.1 [ Time Frame: 18 months from start of randomization part ]
    Progression free survival is defined as the time from randomization to the date of the first documented radiological progression using RECIST 1.1(Response evaluation criteria in solid tumor) or death due to any cause
  • Double-blind, randomized, placebo-controlled part: Overall survival (OS) per investigator assessment using RECIST v1.1 [ Time Frame: 38 months from start of randomization part ]
    Overall survival is defined as the time from date of randomization to date of death due to any cause
Original Primary Outcome Measures  ICMJE
 (submitted: August 10, 2018)
  • Incidence of dose limiting toxicities (DLT) [ Time Frame: 6 months ]
  • Progression free survival (PFS) per investigator assessment using RECIST v1.1 [ Time Frame: 18 months ]
    RECIST v1.1 = Response evaluation criteria in solid tumor v1.1
  • Overall survival (OS) per investigator assessment using RECIST v1.1 [ Time Frame: 38 months ]
    RECIST v1.1 = Response evaluation criteria in solid tumor v1.1
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: November 7, 2018)
  • Safety run-in part: Overall response rate (ORR) per investigator assessment using RECIST v1.1 [ Time Frame: Baseline, every 6 weeks (for the first 12 weeks), then every 9 weeks (for the next 21 weeks) and every 12 weeks thereafter until progression per investigator assessment and up to 6 months ]
    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
  • Double-blind, randomized, placebo-controlled part : Overall response rate (ORR) per investigator assessment using RECIST v1.1 [ Time Frame: Baseline, every 6 weeks (for the first 12 weeks), then every 9 weeks (for the next 21 weeks) and every 12 weeks thereafter until progression per investigator assessment and up to 18 months ]
    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
  • Safety run-in part: Disease control rate (DCR) per investigator assessment using RECIST v1.1 [ Time Frame: Baseline, every 6 weeks (for the first 12 weeks), then every 9 weeks (for the next 21 weeks) and every 12 weeks thereafter until progression per investigator assessment and up to 6 months ]
    Disease control rate is defined as the proportion of patients with complete response (CR) or partial response (PR) or subjects with stable disease (SD) as per investigator assessment according to RECIST 1.1 criteria
  • Double-blind, randomized, placebo-controlled part : Disease control rate (DCR) per investigator assessment using RECIST v1.1 [ Time Frame: Baseline, every 6 weeks (for the first 12 weeks), then every 9 weeks (for the next 21 weeks) and every 12 weeks thereafter until progression per investigator assessment and up to 18 months ]
    Disease control rate is defined as the proportion of patients with complete response (CR) or partial response (PR) or subjects with stable disease (SD) as per investigator assessment according to RECIST 1.1 criteria
  • Safety run-in part: Duration of response (DOR) per investigator assessment using RECIST v1.1 [ Time Frame: Baseline, every 6 weeks (for the first 12 weeks), then every 9 weeks (for the next 21 weeks) and every 12 weeks thereafter until progression per investigator assessment and up to 6 months ]
    Duration of response is defined as the time from first documented response of CR or PR to date of first documented progression or death due to any cause, according to RECIST 1.1 criteria
  • Double-blind, randomized, placebo-controlled part : Duration of response (DOR) per investigator assessment using RECIST v1.1 [ Time Frame: Baseline, every 6 weeks (for the first 12 weeks), then every 9 weeks (for the next 21 weeks) and every 12 weeks thereafter until progression per investigator assessment and up to 18 months ]
    Duration of response is defined as the time from first documented response of CR or PR to date of first documented progression or death, according to RECIST 1.1 criteria
  • Double-blind, randomized, placebo-controlled part only: Time to response (TTR) per investigator assessment using RECIST v1.1 [ Time Frame: Baseline, every 6 weeks (for the first 12 weeks), then every 9 weeks (for the next 21 weeks) and every 12 weeks thereafter until progression per investigator assessment and up to 18 months ]
    Time to response (TTR) is defined as duration of time between the date of randomization and the date of first documented response of either CR or PR, according to RECIST 1.1 criteria
  • Safety run-in part: Antidrug antibodies (ADA) of canakinumab [ Time Frame: Predose (0 h) on Day 1 of Cycles 1, 4, 8, 12, 16 (Cycle length =21 days), at end of treatment & then at 26, 78 and 130 days after last dose ]
  • Double-blind, randomized, placebo-controlled part : Antidrug antibodies (ADA) of canakinumab [ Time Frame: Predose (0 h) on Day 1 of Cycles 1, 4, 8, 12, 16 (Cycle length =21 days), at end of treatment & then at 26, 78 and 130 days after last dose ]
  • Safety run-in part: Antidrug antibodies (ADA) of pembrolizumab [ Time Frame: Predose (0 h) on Day 1 of Cycles 1, 2, 4, 8, 12, 16 (Cycle length =21 days), at end of treatment & then at 26 days after last dose ]
  • Double-blind, randomized, placebo-controlled part : Antidrug antibodies (ADA) of pembrolizumab [ Time Frame: Predose (0 h) on Day 1 of Cycles 1, 2, 4, 8, 12, 16 (Cycle length =21 days), at end of treatment & then at 26 days after last dose ]
  • Safety run-in part: Serum canakinumab concentration [ Time Frame: Predose (0 h) on Day 1 of Cycles 1-6, 8, 12, 16, Postdose on D2, D8, D15 of Cycle 1, Post dose on C5D8, at end of treatment & then at 26, 78 and 130 days after last dose (Cycle length =21 days) ]
  • Double-blind, randomized, placebo-controlled part : Serum canakinumab concentration [ Time Frame: Predose (0 h) on Day 1 of Cycles 1-6, 8, 12, 16, Postdose on D2, D8, D15 of Cycle 1, Postdose on C5D8, at end of treatment & then at 26, 78 and 130 days after last dose (Cycle length =21 days) ]
  • Safety run-in part: Serum pembrolizumab concentration [ Time Frame: Predose (0 h) on Day 1 of Cycles 1-6, 8, 12, 16, Postdose on D2, D8, D15 of Cycle 1, at end of treatment & then at 26 days after last dose (Cycle length =21 days) ]
  • Double-blind, randomized, placebo-controlled part : Serum pembrolizumab concentration [ Time Frame: Predose (0 h) on Day 1 of Cycles 1-6, 8, 12, 16, Postdose on D2, D8, D15 of Cycle 1, at end of treatment & then at 26 days after last dose (Cycle length =21 days) ]
  • Safety run-in part: Plasma pemetrexed concentration [ Time Frame: Pre (0 h) and end of infusion on Cy 1 and 2, 1, 4, 8 h post infusion on Cy 1, 1, 2, 4, 8h post infusion on Cy 2 (Cy length =21 days) ]
  • Double-blind, randomized, placebo-controlled part : : Plasma pemetrexed concentration [ Time Frame: Pre (0 h) and end of infusion of Cy 1 and 2, 1, 4, 8 h post infusion on Cy 1, 1, 2, 4, 8 h post infusion on Cy 2 (Cy length =21 days) ]
  • Safety run-in part: Plasma cisplatin concentration [ Time Frame: Pre (0 h) and end of infusion on Cy 1 and 2, 2, 4, 8 h post infusion on Cy 1, 1.5, 2, 4, 8 h post infusion on Cy 2 (Cy length =21 days) ]
  • Double-blind, randomized, placebo-controlled part: Plasma cisplatin concentration [ Time Frame: Pre (0 h) and end of infusion on Cy 1 and 2, 2, 4, 8 h post infusion on Cy 1, 1.5, 2, 4, 8 h post infusion on Cy 2 (Cy length = 21 days) ]
  • Safety run-in part: Plasma carboplatin concentration [ Time Frame: Pre (0 h), end of infusion, 1, 2, 4, 8 h post infusion on Cycles 1 and 2 (Cycle length =21 days) ]
  • Double-blind, randomized, placebo-controlled part: Plasma carboplatin concentration [ Time Frame: Pre (0 h), end of infusion, 1, 2, 4, 8 h post infusion on Cycles 1 and 2 (Cycle length =21 days) ]
  • Safety run-in part: Plasma paclitaxel concentration [ Time Frame: Pre (0 h) and end of infusion on Cy 1 and 2, 4, 8, 12 h post infusion on Cycles 1, 4, 6, 8, 12 h post infusion on Cycle 2 (Cycle length =21 days) ]
  • Double-blind, randomized, placebo-controlled part: Plasma paclitaxel concentration [ Time Frame: Pre (0 h) and end of infusion on Cy 1 and 2, 4, 8, 12 h post infusion on Cy 1, 4, 6, 8, 12 h post infusion on Cy 2 (Cy length =21 days) ]
  • Double-blind, randomized, placebo-controlled part: Plasma nab-paclitaxel concentration [ Time Frame: Pre (0 h) and end of infusion on Cy 1 and 2, 4, 8, 12 h post infusion on Cy 1, 4, 6, 8, 12 h post infusion on Cy 2 (Cy length =21 days) ]
  • Double-blind, randomized, placebo-controlled part only :Time to definitive 10 point deterioration symptom scores of pain, cough and dyspnea per QLQ-LC13 questionnaire [ Time Frame: Baseline and at day 1 of every visit (with dosing or not) until end of treatment, before each tumor assessments and 2 times (7 days and 28 days) after disease progression and up to 18 months ]
    To assess the effect of canakinumab vs placebo on time to onset or deterioration of lung cancer specific symptoms
  • Double-blind, randomized, placebo-controlled part only: Time to definitive deterioration in global health status/QoL, shortness of breath and pain per QLQ-C30 questionnaire [ Time Frame: Baseline and at day 1 of every visit (with dosing or not) until end of treatment, before each tumor assessments and 2 times (7 days and 28 days) after disease progression and up to 18 months ]
    To assess the effect of canakinumab vs placebo on time to onset or deterioration of lung cancer specific symptoms
  • Double-blind, randomized, placebo-controlled part only: change from baseline in score as per the EQ-5D-5L questionnaire [ Time Frame: Baseline and at day 1 of every visit (with dosing or not) until end of treatment, before each tumor assessments and 2 times (7 days and 28 days) after disease progression and up to 18 months ]
    To assess the effect of canakinumab versus placebo on patient reported outcomes ((PROs) - patient's health related quality of life)
Original Secondary Outcome Measures  ICMJE
 (submitted: August 10, 2018)
  • Overall response rate (ORR) per investigator assessment using RECIST v1.1 [ Time Frame: Baseline, every 6 weeks (for the first 12 weeks), then every 9 weeks (for the next 21 weeks) and every 12 weeks thereafter until progression per investigator assessment up to 1 year after last patient last visit ]
  • Disease control rate (DRC) per investigator assessment using RECIST v1.1 [ Time Frame: Baseline, every 6 weeks (for the first 12 weeks), then every 9 weeks (for the next 21 weeks) and every 12 weeks thereafter until progression per investigator assessment up to 1 year after last patient last visit ]
  • Duration of response (DOR) per investigator assessment using RECIST v1.1 [ Time Frame: Baseline, every 6 weeks (for the first 12 weeks), then every 9 weeks (for the next 21 weeks) and every 12 weeks thereafter until progression per investigator assessment up to 1 year after last patient last visit ]
  • Time to response (TTR) per investigator assessment using RECIST v1.1 [ Time Frame: Baseline, every 6 weeks (for the first 12 weeks), then every 9 weeks (for the next 21 weeks) and every 12 weeks thereafter until progression per investigator assessment up to 1 year after last patient last visit ]
  • Antidrug antibodies (ADA) [ Time Frame: Cycle1 Day1, Cycle2 Day1, Cycle4 Day1, Cycle8 Day1, Cycle12 Day1, Cycle16 Day1 (each cycle is 3 weeks) and through end of treatment, an average of 1 year ]
  • Cmax [ Time Frame: Cycle1 Day1, Cycle1 Day2, Cycle1 Day8, Cycle1 Day15, Cycle2 Day1, Cycle3 Day1, Cycle4 Day1, Cycle5 Day1, Cycle6 Day1, Cycle8 Day1, Cycle12 Day1, Cycle16 Day1(each cycle is 3 weeks) and through treatment end, an average of 1 year ]
  • Area under the curve (AUC) [ Time Frame: Cycle1 Day1, Cycle1 Day2, Cycle1 Day8, Cycle1 Day15, Cycle2 Day1, Cycle3 Day1, Cycle4 Day1, Cycle5 Day1, Cycle6 Day1, Cycle8 Day1, Cycle12 Day1, Cycle16 Day1(each cycle is 3 weeks) and through treatment end, an average of 1 year ]
  • Ctrough [ Time Frame: Cycle1 Day1, Cycle1 Day2, Cycle1 Day8, Cycle1 Day15, Cycle2 Day1, Cycle3 Day1, Cycle4 Day1, Cycle5 Day1, Cycle6 Day1, Cycle8 Day1, Cycle12 Day1, Cycle16 Day1(each cycle is 3 weeks) and through treatment end, an average of 1 year ]
  • Patient reported outcome (PRO) [ Time Frame: Baseline and every visit until end of treatment and 2 times after disease progression, an average of 1 year ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Study of Efficacy and Safety of Pembrolizumab Plus Platinum-based Doublet Chemotherapy With or Without Canakinumab in Previously Untreated Locally Advanced or Metastatic Non-squamous and Squamous NSCLC Subjects
Official Title  ICMJE A Randomized, Double-blind, Placebo-controlled, Phase III Study Evaluating the Efficacy and Safety of Pembrolizumab Plus Platinum-based Doublet Chemotherapy With or Without Canakinumab as First Line Therapy for Locally Advanced or Metastatic Non-squamous and Squamous Non-small Cell Lung Cancer Subjects (CANOPY-1)
Brief Summary

This is a phase III study of pembrolizumab plus platinum-based doublet chemotherapy with or without canakinumab in previously untreated locally advanced or metastatic non-squamous and squamous NSCLC subjects.

The study will assess primarily the safety and tolerability (safety run-in part) of pembrolizumab plus platinum-based doublet chemotherapy with canakinumab and then the efficacy (double-blind, randomized, placebo controlled part) of pembrolizumab plus platinum-based doublet chemotherapy with or without canakinumab.

Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
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
    canakinumab every 3 weeks (squamous and non-squamous)
    Other Name: ACZ885
  • Drug: canakinumab matching placebo
    canakinumab placebo every 3 weeks (squamous and non-squamous)
  • Drug: pembrolizumab
    200 mg every 3 weeks (squamous and non-squamous)
  • Drug: carboplatin
    AUC 5 mg/mL*min every 3 weeks (non-squamous) or AUC 6 mg/mL*min (squamous)
  • Drug: cisplatin
    75 mg/m2 every 3 weeks (non-squamous)
  • Drug: paclitaxel
    200 mg/m2 every 3 weeks (squamous)
  • Drug: nab-paclitaxel
    100 mg/m2 every 3 weeks (squamous)
  • Drug: pemetrexed
    500 mg/m2 every 3 weeks (non-squamous)
Study Arms  ICMJE
  • Experimental: canakinumab
    canakinumab in combination with pembrolizumab and platinum-based doublet chemotherapy
    Interventions:
    • Drug: canakinumab
    • Drug: pembrolizumab
    • Drug: carboplatin
    • Drug: cisplatin
    • Drug: paclitaxel
    • Drug: nab-paclitaxel
    • Drug: pemetrexed
  • canakinumab matching-placebo
    canakinumab matching-placebo in combination with pembrolizumab and platinum-based doublet chemotherapy
    Interventions:
    • Drug: canakinumab matching placebo
    • Drug: pembrolizumab
    • Drug: carboplatin
    • Drug: cisplatin
    • Drug: paclitaxel
    • Drug: nab-paclitaxel
    • Drug: pemetrexed
Publications * Not Provided

*   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: April 23, 2020)
673
Original Estimated Enrollment  ICMJE
 (submitted: August 10, 2018)
627
Estimated Study Completion Date  ICMJE September 22, 2022
Actual Primary Completion Date August 9, 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Key inclusion criteria:

  • Histologically confirmed locally advanced stage IIIB or stage IV NSCLC for treatment in the first-line setting
  • Known PD-L1 status determined by a Novartis designated central laboratory. A newly obtained tissue biopsy or an archival biopsy (block or slides) is required for PD-L1 determination (PD-L1 IHC 22C3 pharmDx assay), prior to study randomization. Note: For the safety run-in part, known PD-L1 status is not required.
  • Eastern Cooperative oncology group (ECOG) performance status of 0 or 1.
  • At least 1 measurable lesion by RECIST 1.1

Key exclusion criteria:

  • Previous immunotherapy (e.g. anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CTLA-4 antibody, or any other antibody or drug specifically targeting T-cell co-stimulation or immune checkpoint pathways).
  • Prior treatment with canakinumab or drugs of a similar mechanism of action (IL-1β inhibitor).
  • Subjects with epidermal growth factor receptor (EGFR) sensitizing mutations (identified in exons 19, 20, or 21), and/or ALK rearrangement by locally approved laboratory testing.
  • Previously untreated or symptomatic central nervous system (CNS) metastases or lepto-meningeal disease.
  • Subject with suspected or proven immune-compromised state or infections.
  • Subject has prior to starting study drug: received live vaccination ≤3 months, had major surgery ≤4 weeks prior to starting study drug, has thoracic radiotherapy: lung fields ≤ 4 weeks, other anatomic sites ≤ 2 weeks, palliative radiotherapy for bone lesions ≤ 2 weeks.

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 Argentina,   Australia,   Austria,   Brazil,   Canada,   Chile,   China,   Colombia,   Czechia,   Denmark,   Finland,   France,   Germany,   Greece,   Hong Kong,   Hungary,   Iceland,   India,   Italy,   Japan,   Korea, Republic of,   Lebanon,   Malaysia,   Netherlands,   Norway,   Philippines,   Poland,   Portugal,   Romania,   Russian Federation,   Singapore,   Slovakia,   Spain,   Sweden,   Switzerland,   Taiwan,   Thailand,   Turkey,   United Kingdom,   United States,   Vietnam
Removed Location Countries South Africa
 
Administrative Information
NCT Number  ICMJE NCT03631199
Other Study ID Numbers  ICMJE CACZ885U2301
2018-001547-32 ( EudraCT Number )
Has Data Monitoring Committee Yes
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.

Responsible Party Novartis ( Novartis Pharmaceuticals )
Study Sponsor  ICMJE Novartis Pharmaceuticals
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals
PRS Account Novartis
Verification Date September 2021

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