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

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

  • Non-small Cell Lung Cancer

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.