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

Phase 3TerminatedNCT03631199

Novartis Pharmaceuticals673 enrolled

Overview

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.

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.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

QUADRUPLE

Enrollment

673

Conditions

Non-small Cell Lung Cancer

Interventions

canakinumabDRUG

canakinumab 200 mg subcutaneous (s.c.) injection every 3 weeks (squamous and non-squamous)

canakinumab-matching placeboDRUG

canakinumab placebo every 3 weeks (squamous and non-squamous)

pembrolizumabDRUG

200 mg every 3 weeks (squamous and non-squamous)

Eligibility

Sex: ALLMin age: 18 YearsMax age: 100 Years

Medical Language ↔ Plain English

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.

Locations (152)

Outcomes

Primary Outcomes

Part 1 (Safety Run-in): Number of Participants With Dose-limiting Toxicities (DLTs)

A DLT was defined as an adverse event or abnormal laboratory value assessed as unrelated to disease progression, inter-current illness, or concomitant medications that met certain criteria as defined in the protocol.

Time frame: During the first 42 days of dosing

Part 2 (Double-blind, Randomized, Placebo-controlled): Progression-free Survival (PFS) Per Investigator Assessment Using RECIST v1.1

Progression free survival was 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.

Time frame: 18 months

Part 2 (Double-blind, Randomized, Placebo-controlled): Overall Survival (OS) Per Investigator Assessment Using RECIST v1.1

Overall survival is defined as the time from date of randomization to date of death due to any cause.

Time frame: Up to approximately 32 months

Secondary Outcomes

Part 1 (Safety Run-in): Overall Response Rate (ORR) Per Investigator Assessment Using RECIST v1.1

ORR was defined as the percentage of participants with confirmed best overall response of complete response (CR) or partial response (PR), as per investigator's assessment by RECIST 1.1. CR=Disappearance of all non-nodal target lesions. In addition, any pathological lymph nodes assigned as target lesions must have a reduction in short axis to \< 10 mm; PR= At least a 30% decrease in the sum of diameter of all target lesions, taking as reference the baseline sum of diameters.

Time frame: Up to approximately 14 months

Part 2 (Double-blind, Randomized, Placebo-controlled): Overall Response Rate (ORR) Per Investigator Assessment Using RECIST v1.1

Data from ClinicalTrials.gov

This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.

Area Under the Curve (AUC) 5 mg/mL\*min every 3 weeks (non-squamous) or AUC 6 mg/mL\*min (squamous)

cisplatinDRUG

75 mg/m\^2 every 3 weeks (non-squamous)

paclitaxelDRUG

200 mg/m\^2 every 3 weeks (squamous)

nab-paclitaxelDRUG

100 mg/m\^2 on Days 1, 8, and 15 of every cycle (squamous)

pemetrexedDRUG

500 mg/m\^2 every 3 weeks (non-squamous)

Pacific Shores Medical Group

Long Beach, California, United States

USC Kenneth Norris Comprehensive Cancer Center

Los Angeles, California, United States

AdventHealth

Orlando, Florida, United States

Dana Farber Cancer Institute

Boston, Massachusetts, United States

Novartis Investigative Site

Caba, Buenos Aires, Argentina

Novartis Investigative Site

Caba, Argentina

Novartis Investigative Site

Westmead, New South Wales, Australia

Novartis Investigative Site

Wooloongabba, Queensland, Australia

Novartis Investigative Site

Melbourne, Victoria, Australia

Novartis Investigative Site

Murdoch, Western Australia, Australia

...and 142 more locations