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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 : Not yet recruiting
First Posted : August 15, 2018
Last Update Posted : November 9, 2018
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )

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.


Condition or disease Intervention/treatment Phase
Non-small Cell Lung Cancer Drug: canakinumab Drug: canakinumab matching placebo Drug: pembrolizumab Drug: carboplatin Drug: cisplatin Drug: paclitaxel Drug: nab-paclitaxel Drug: pemetrexed Phase 3

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 627 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: 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)
Estimated Study Start Date : January 14, 2019
Estimated Primary Completion Date : May 31, 2021
Estimated Study Completion Date : October 21, 2022

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: canakinumab
canakinumab in combination with pembrolizumab and platinum-based doublet chemotherapy
Drug: canakinumab
canakinumab every 3 weeks (squamous and non-squamous)
Other Name: ACZ885

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)

canakinumab matching-placebo
canakinumab matching-placebo in combination with pembrolizumab and platinum-based doublet chemotherapy
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)




Primary Outcome Measures :
  1. 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

  2. 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

  3. 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


Secondary Outcome Measures :
  1. 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

  2. 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

  3. 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

  4. 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

  5. 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

  6. 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

  7. 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

  8. 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 ]
  9. 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 ]
  10. 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 ]
  11. 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 ]
  12. 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) ]
  13. 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) ]
  14. 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) ]
  15. 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) ]
  16. 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) ]
  17. 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) ]
  18. 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) ]
  19. 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) ]
  20. 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) ]
  21. 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) ]
  22. 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) ]
  23. 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) ]
  24. 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) ]
  25. 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

  26. 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

  27. 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)



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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.


Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03631199


Contacts
Contact: Novartis Pharmaceuticals 1-888-669-6682 novartis.email@novartis.com
Contact: Novartis Pharmaceuticals +41613241111

Sponsors and Collaborators
Novartis Pharmaceuticals
Investigators
Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals

Responsible Party: Novartis Pharmaceuticals
ClinicalTrials.gov Identifier: NCT03631199     History of Changes
Other Study ID Numbers: CACZ885U2301
2018-001547-32 ( EudraCT Number )
First Posted: August 15, 2018    Key Record Dates
Last Update Posted: November 9, 2018
Last Verified: November 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided
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.


Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Novartis ( Novartis Pharmaceuticals ):
CANOPY-1
ACZ885
canakinumab
pembrolizumab
carboplatin
cisplatin
paclitaxel
nab-paclitaxel
pemetrexed
NSCLC
non-small cell lung cancer
non small cell lung cancer
squamous
non-squamous
hsCRP
IL-1β
PD-L1
CANOPY
platinum-based doublet chemotherapy
first line therapy
locally advanced
metastatic

Additional relevant MeSH terms:
Lung Neoplasms
Carcinoma, Non-Small-Cell Lung
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Neoplasms
Lung Diseases
Respiratory Tract Diseases
Carcinoma, Bronchogenic
Bronchial Neoplasms
Paclitaxel
Pembrolizumab
Albumin-Bound Paclitaxel
Cisplatin
Carboplatin
Pemetrexed
Antibodies, Monoclonal
Antineoplastic Agents, Phytogenic
Antineoplastic Agents
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Enzyme Inhibitors
Folic Acid Antagonists
Nucleic Acid Synthesis Inhibitors
Immunologic Factors
Physiological Effects of Drugs