Clinical Trials /

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

NCT03631199

Description:

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.

Related Conditions:
  • Non-Small Cell Lung Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 3

Trial Eligibility

Document

Title

  • Brief Title: 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: 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)

Clinical Trial IDs

  • ORG STUDY ID: CACZ885U2301
  • SECONDARY ID: 2018-001547-32
  • NCT ID: NCT03631199

Conditions

  • Non-small Cell Lung Cancer

Interventions

DrugSynonymsArms
canakinumabACZ885canakinumab
canakinumab matching placebocanakinumab matching-placebo
pembrolizumabcanakinumab
carboplatincanakinumab
cisplatincanakinumab
paclitaxelcanakinumab
nab-paclitaxelcanakinumab
pemetrexedcanakinumab

Purpose

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.

Trial Arms

NameTypeDescriptionInterventions
canakinumabExperimentalcanakinumab in combination with pembrolizumab and platinum-based doublet chemotherapy
  • canakinumab
  • pembrolizumab
  • carboplatin
  • cisplatin
  • paclitaxel
  • nab-paclitaxel
  • pemetrexed
canakinumab matching-placeboOthercanakinumab matching-placebo in combination with pembrolizumab and platinum-based doublet chemotherapy
  • canakinumab matching placebo
  • pembrolizumab
  • carboplatin
  • cisplatin
  • paclitaxel
  • nab-paclitaxel
  • pemetrexed

Eligibility 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.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Safety run-in part: Incidence of dose limiting toxicities (DLTs)
Time Frame:6 months from start of safety run-in part
Safety Issue:
Description:Incidence of DLTs assessed among at least 6 evaluable subjects during the first 42 days of study treatment

Secondary Outcome Measures

Measure: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
Safety Issue:
Description: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
Measure: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
Safety Issue:
Description: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
Measure: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
Safety Issue:
Description: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
Measure: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
Safety Issue:
Description: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
Measure: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
Safety Issue:
Description: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
Measure: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
Safety Issue:
Description: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
Measure: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
Safety Issue:
Description: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
Measure: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
Safety Issue:
Description:
Measure: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 Issue:
Description:
Measure: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
Safety Issue:
Description:
Measure: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 Issue:
Description:
Measure: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)
Safety Issue:
Description:
Measure: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 Issue:
Description:
Measure: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)
Safety Issue:
Description:
Measure: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 Issue:
Description:
Measure: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)
Safety Issue:
Description:
Measure: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 Issue:
Description:
Measure: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)
Safety Issue:
Description:
Measure: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 Issue:
Description:
Measure: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)
Safety Issue:
Description:
Measure: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 Issue:
Description:
Measure: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)
Safety Issue:
Description:
Measure: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)
Safety Issue:
Description:
Measure: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)
Safety Issue:
Description:
Measure: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
Safety Issue:
Description:To assess the effect of canakinumab vs placebo on time to onset or deterioration of lung cancer specific symptoms
Measure: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
Safety Issue:
Description:To assess the effect of canakinumab vs placebo on time to onset or deterioration of lung cancer specific symptoms
Measure: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
Safety Issue:
Description:To assess the effect of canakinumab versus placebo on patient reported outcomes ((PROs) - patient's health related quality of life)

Details

Phase:Phase 3
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Novartis Pharmaceuticals

Trial Keywords

  • 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
  • CANOPY-1
  • platinum-based doublet chemotherapy
  • first line therapy
  • locally advanced
  • metastatic

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