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Phase III Study Evaluating Efficacy and Safety of Canakinumab in Combination With Docetaxel in Adult Subjects With Non-small Cell Lung Cancers as a Second or Third Line Therapy

NCT03626545

Description:

This phase III study is designed to evaluate the role of IL-1β inhibition in combination with docetaxel in subjects with advanced NSCLC previously treated with PD-(L)1 inhibitors and platinum-based chemotherapy. The randomized III part will be preceded by a safety run-in part in which the recommended dose of the combination of canakinumab and docetaxel will be confirmed.

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

Recruiting

Phase:

Phase 3

Trial Eligibility

Document

Title

  • Brief Title: Phase III Study Evaluating Efficacy and Safety of Canakinumab in Combination With Docetaxel in Adult Subjects With Non-small Cell Lung Cancers as a Second or Third Line Therapy
  • Official Title: A Randomized, Double-blind, Placebo-controlled, Phase III Study Evaluating the Efficacy and Safety of Canakinumab in Combination With Docetaxel Versus Placebo in Combination With Docetaxel in Adult Subjects With Non-small Cell Lung Cancer (NSCLC) Previously Treated With PD-(L)1 Inhibitors and Platinum-based Chemotherapy (CANOPY 2)

Clinical Trial IDs

  • ORG STUDY ID: CACZ885V2301
  • SECONDARY ID: 2018-002480-26
  • NCT ID: NCT03626545

Conditions

  • Non-Small-Cell Lung

Interventions

DrugSynonymsArms
CanakinumabACZ885Canakinumab
DocetaxelCanakinumab

Purpose

This phase III study is designed to evaluate the role of IL-1β inhibition in combination with docetaxel in subjects with advanced NSCLC previously treated with PD-(L)1 inhibitors and platinum-based chemotherapy. The randomized III part will be preceded by a safety run-in part in which the recommended dose of the combination of canakinumab and docetaxel will be confirmed.

Trial Arms

NameTypeDescriptionInterventions
CanakinumabExperimentalBlinded Canakinumab administered at the recommended Phase III regimen (defined in the safety run-in part). Canakinumab will be given in combination with docetaxel (standard of care)
  • Canakinumab
  • Docetaxel
PlaceboPlacebo ComparatorMatching placebo, administered at the recommended Phase III regimen (defined in the safety run-in part), in combination with docetaxel (standard of care)
  • Docetaxel

Eligibility Criteria

        Key Inclusion Criteria:

          -  Histologically confirmed advanced (stage IIIB) or metastatic NSCLC.

          -  Subject has received one prior platinum-based chemotherapy and one prior PD-(L)1
             inhibitor therapy for locally advanced or metastatic disease.

          -  Subject with ECOG performance status (PS) of 0 or 1.

          -  Subject with at least 1 evaluable (measurable or non-measurable) lesion by RECIST 1.1
             in solid tumors criteria.

        Key Exclusion Criteria:

          -  Subject who previously received docetaxel, canakinumab (or another IL-1β inhibitor),
             or any systemic therapy for their locally advanced or metastatic NSCLC other than one
             platinum-based chemotherapy and one prior PD-(L)1 inhibitor.

          -  Subject with EGFRor ALK positive tumor.

          -  History of severe hypersensitivity reaction to monoclonal antibodies, taxanes or
             excipients of docetaxel or canakinumab.

        Other protocol-defined inclusion/exclusion 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
Safety Issue:
Description:Incidence of DLT assessed among a minimum of 6 evaluable subjects during 42 days of docetaxel and canakinumab treatment

Secondary Outcome Measures

Measure:Overall response rate (ORR)
Time Frame:every 6 weeks during the first 12 months and every 12 weeks thereafter until disease progression or death due to any cause, whichever occurs first (26 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:Duration of response (DOR)
Time Frame:every 6 weeks during the first 12 months and every 12 weeks thereafter until disease progression or death due to any cause, whichever occurs first (26 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:Disease control rate (DCR)
Time Frame:every 6 weeks during the first 12 months and every 12 weeks thereafter until disease progression or death due to any cause, whichever occurs first (26 months)
Safety Issue:
Description:Disease control rate is defined as the proportion of patients with CR or PR or subjects with SD as per local review according to RECIST 1.1 criteria
Measure:Randomized Part only: Progression-Free Survival (PFS)
Time Frame:every 6 weeks during the first 12 months, then every 12 weeks thereafter until disease progression or death due to any cause, whichever occurs first (26 months)
Safety Issue:
Description:Progression-free survival is defined as the time from randomization to the date of the first documented radiological progression using RECIST 1.1 response criteria or death due to any cause
Measure:Randomized part only: Time to Response (TTR)
Time Frame:every 6 weeks during the first 12 months and every 12 weeks thereafter until disease progression or death due to any cause, whichever occurs first (26 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:Randomized part only: Time to definitive 10 point deterioration symptom scores of pain,cough and dyspnea per QLQ-LC13 questionnaire
Time Frame:26 months
Safety Issue:
Description:To assess the effect of canakinumab vs placebo on time to onset or deterioration of lung cancer specific symptoms
Measure:Randomized part only: Time to definitive deterioration in global health status/QoL, shortness of breath and pain per QLQ-C30 questionnaire
Time Frame:26 months
Safety Issue:
Description:To assess the effect of canakinumab vs placebo on time to onset or deterioration of lung cancer specific symptoms
Measure:Randomized part only: change from baseline in score per the EORTC QLQ C30 questionnaire
Time Frame:26 months
Safety Issue:
Description:To assess the effect of canakinumab versus placebo on PROs (patient's health related quality of life)
Measure:Randomized part only: change fropm baseline in score as per the EORTC-QLQ LC13 questionnaire
Time Frame:26 months
Safety Issue:
Description:To assess the effect of canakinumab versus placebo on PROs (patient's health related quality of life)
Measure:Randomized part only: change from baseline in score as per the EQ-5D-5L questionnaire
Time Frame:26 months
Safety Issue:
Description:To assess the effect of canakinumab versus placebo on PROs (patient's health related quality of life)
Measure:Serum concentration-time profiles of canakinumab
Time Frame:26 months
Safety Issue:
Description:To characterize the pharmacokinetics of canakinumab
Measure:Maximum serum concentration (Cmax) of canakimumab
Time Frame:26 months
Safety Issue:
Description:The Cmax values are based on the serum concentration-time profile of canakimuab. To characterize the pharmacokinetics of canakinumab
Measure:Steady-state trough concentrations (Ctrough) of canakinumab
Time Frame:26 months
Safety Issue:
Description:To caracterize the pharmacokinetics of canakinumab
Measure:Time of maximum serum concentration (Tmax) of canakinumab
Time Frame:26 months
Safety Issue:
Description:The Tmax values are based on the serum concentration-time profile of canakimuab. To characterize the pharmacokinetics of canakinumab.
Measure:Plasma concentration-time profiles of docetaxel
Time Frame:26 months
Safety Issue:
Description:To characterize the pharmacokinetics of docetaxel
Measure:Maximum plasma concentration (Cmax) of docetaxel
Time Frame:26 months
Safety Issue:
Description:The Cmax values are based on the plasma concentration-time profile of docetaxel. To characterize the pharmacokinetics of docetaxel.
Measure:Antidrug antibodies (ADA)
Time Frame:26 months
Safety Issue:
Description:

Details

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

Trial Keywords

  • ACZ885
  • canakinumab
  • docetaxel
  • NSCLC
  • Non Small Cell Lung Cancer
  • Carcinoma
  • IL-1β
  • PD-(L)1
  • CANOPY
  • CANOPY-2
  • second or third line therapy
  • PD-(L)1 inhibitors
  • platinum-based chemotherapy

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