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Purpose

This was 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 participants.

Condition

Eligibility

Eligible Ages
Between 18 Years and 100 Years
Eligible Sex
All
Accepts Healthy Volunteers
No

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

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.

Study Design

Phase
Phase 3
Study Type
Interventional
Allocation
Randomized
Intervention Model
Parallel Assignment
Primary Purpose
Treatment
Masking
Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Arm Groups

ArmDescriptionAssigned Intervention
Experimental
Part 1: Cohort A 		Safety run-in, canakinumab in combination with pembrolizumab, carboplatin, and pemetrexed.
  • Drug: canakinumab
    canakinumab 200 mg subcutaneous (s.c.) injection every 3 weeks (squamous and non-squamous)
    Other names:
    • ACZ885
  • Drug: pembrolizumab
    200 mg every 3 weeks (squamous and non-squamous)
  • Drug: carboplatin
    Area Under the Curve (AUC) 5 mg/mL*min every 3 weeks (non-squamous) or AUC 6 mg/mL*min (squamous)
  • Drug: pemetrexed
    500 mg/m^2 every 3 weeks (non-squamous)
Experimental
Part 1: Cohort B 		Safety run-in, canakinumab in combination with pembrolizumab, cisplatin, and pemetrexed.
  • Drug: canakinumab
    canakinumab 200 mg subcutaneous (s.c.) injection every 3 weeks (squamous and non-squamous)
    Other names:
    • ACZ885
  • Drug: pembrolizumab
    200 mg every 3 weeks (squamous and non-squamous)
  • Drug: cisplatin
    75 mg/m^2 every 3 weeks (non-squamous)
  • Drug: pemetrexed
    500 mg/m^2 every 3 weeks (non-squamous)
Experimental
Part 1: Cohort C 		Safety run-in, canakinumab in combination with pembrolizumab, carboplatin, and paclitaxel.
  • Drug: canakinumab
    canakinumab 200 mg subcutaneous (s.c.) injection every 3 weeks (squamous and non-squamous)
    Other names:
    • ACZ885
  • Drug: pembrolizumab
    200 mg every 3 weeks (squamous and non-squamous)
  • Drug: carboplatin
    Area Under the Curve (AUC) 5 mg/mL*min every 3 weeks (non-squamous) or AUC 6 mg/mL*min (squamous)
  • Drug: paclitaxel
    200 mg/m^2 every 3 weeks (squamous)
Experimental
Part 2: Canakinumab+pembro+CTx 		Double-blind, randomized, placebo-controlled, canakinumab in combination with pembrolizumab and platinum-based doublet chemotherapy.
  • Drug: canakinumab
    canakinumab 200 mg subcutaneous (s.c.) injection every 3 weeks (squamous and non-squamous)
    Other names:
    • ACZ885
  • Drug: pembrolizumab
    200 mg every 3 weeks (squamous and non-squamous)
  • Drug: carboplatin
    Area Under the Curve (AUC) 5 mg/mL*min every 3 weeks (non-squamous) or AUC 6 mg/mL*min (squamous)
  • Drug: cisplatin
    75 mg/m^2 every 3 weeks (non-squamous)
  • Drug: paclitaxel
    200 mg/m^2 every 3 weeks (squamous)
  • Drug: nab-paclitaxel
    100 mg/m^2 on Days 1, 8, and 15 of every cycle (squamous)
  • Drug: pemetrexed
    500 mg/m^2 every 3 weeks (non-squamous)
Other
Part 2: Placebo+pembro+CTx 		Double-blind, randomized, placebo-controlled, 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
    Area Under the Curve (AUC) 5 mg/mL*min every 3 weeks (non-squamous) or AUC 6 mg/mL*min (squamous)
  • Drug: cisplatin
    75 mg/m^2 every 3 weeks (non-squamous)
  • Drug: paclitaxel
    200 mg/m^2 every 3 weeks (squamous)
  • Drug: nab-paclitaxel
    100 mg/m^2 on Days 1, 8, and 15 of every cycle (squamous)
  • Drug: pemetrexed
    500 mg/m^2 every 3 weeks (non-squamous)

More Details

Status
Active, not recruiting
Sponsor
Novartis Pharmaceuticals

Study Contact

Detailed Description

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

Notice

Study information shown on this site is derived from ClinicalTrials.gov (a public registry operated by the National Institutes of Health). The listing of studies provided is not certain to be all studies for which you might be eligible. Furthermore, study eligibility requirements can be difficult to understand and may change over time, so it is wise to speak with your medical care provider and individual research study teams when making decisions related to participation.