Clinical trial NCT03631199: 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)
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE3
Conditions: Non-small Cell Lung Cancer
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
Lead sponsor: Novartis
Sponsor class: INDUSTRY
First posted: 2018-08-15
Enrollment: 673
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.

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.

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.

Primary outcomes:
measure: Part 1 (Safety Run-in): Number of Participants With Dose-limiting Toxicities (DLTs)
timeFrame: During the first 42 days of dosing
measure: Part 2 (Double-blind, Randomized, Placebo-controlled): Progression-free Survival (PFS) Per Investigator Assessment Using RECIST v1.1
timeFrame: 18 months
measure: Part 2 (Double-blind, Randomized, Placebo-controlled): Overall Survival (OS) Per Investigator Assessment Using RECIST v1.1
timeFrame: Up to approximately 32 months
Secondary outcomes:
measure: Part 1 (Safety Run-in): Overall Response Rate (ORR) Per Investigator Assessment Using RECIST v1.1
timeFrame: Up to approximately 14 months
measure: Part 2 (Double-blind, Randomized, Placebo-controlled): Overall Response Rate (ORR) Per Investigator Assessment Using RECIST v1.1
timeFrame: Up to approximately 26 months
measure: Part 1 (Safety run-in): Disease Control Rate (DCR) Per Investigator Assessment Using RECIST v1.1
timeFrame: Up to approximately 14 months
measure: Part 2 (Double-blind, Randomized, Placebo-controlled): Disease Control Rate (DCR) Per Investigator Assessment Using RECIST v1.1
timeFrame: Up to approximately 26 months
measure: Part 1 (Safety run-in): Duration of Response (DOR) Per Investigator Assessment Using RECIST v1.1
timeFrame: Up to approximately 25 months
measure: Part 2 (Double-blind, Randomized, Placebo-controlled): Duration of Response (DOR) Per Investigator Assessment Using RECIST v1.1
timeFrame: Up to approximately 26 months
measure: Part 2 (Double-blind, Randomized, Placebo-controlled): Time to Response (TTR) Per Investigator Assessment Using RECIST v1.1
timeFrame: Up to approximately 26 months
measure: Part 1 (Safety Run-in): Antidrug Antibodies (ADA) of Canakinumab
timeFrame: Predose (0 hours (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
measure: Part 2 (Double-blind, Randomized, Placebo-controlled): Number of Participants With Antidrug Antibodies (ADA) of Canakinumab
timeFrame: Up to approximately 26 months
measure: Part 1 (Safety run-in): Antidrug Antibodies (ADAs) of Pembrolizumab
timeFrame: 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
measure: Part 2 (Double-blind, Randomized, Placebo-controlled): Antidrug Antibodies (ADA) of Pembrolizumab
timeFrame: Up to approximately 26 months
measure: Part 1 (Safety Run-in): Serum Canakinumab Concentration
timeFrame: Predose (0 h) on Day 1 of Cycles 1-6, 8, 12, 16, Postdose on day 2, 8, 15 of Cycle 1, Post dose on Cycle 5 day 8, at end of treatment & then at 26, 78 and 130 days after last dose (Cycle length =21 days)
measure: Part 2 (Double-blind, Randomized, Placebo-controlled): Serum Canakinumab Concentration
timeFrame: Predose (0 h) on Day 1 of Cycles 1-6, 8, 12, 16, Postdose on day 2, 8, 15 of Cycle 1, Post dose on Cycle 5 day 8, at end of treatment & then at 26, 78 and 130 days after last dose (Cycle length =21 days)
measure: Part 1 (Safety Run-in): Serum Pembrolizumab Concentration
timeFrame: Predose (0 h) on Day 1 of Cycles 1-6, 8, 12, 16, Postdose on day 2, 8, 15 of Cycle 1, at end of treatment & then at 26 days after last dose (Cycle length =21 days)
measure: Part 2 (Double-blind, Randomized, Placebo-controlled): Serum Pembrolizumab Concentration
timeFrame: Predose (0 h) on Day 1 of Cycles 1-6, 8, 12, 16, Postdose on day 2, 8, 15 of Cycle 1, at end of treatment & then at 26 days after last dose (Cycle length =21 days)
measure: Part 1 (Safety Run-in): Plasma Pemetrexed Concentration
timeFrame: Predose (0 h) and end of infusion on Cycle 1 and 2; 1, 4, 8 h post infusion on Cycle 1; 1, 2, 4, 8h post infusion on Cycle 2 (Cycle length =21 days)
measure: Part 2 (Double-blind, Randomized, Placebo-controlled): Plasma Pemetrexed Concentration
timeFrame: Predose (0 h) and end of infusion on Cycle 1 and 2; 1, 4, 8 h post infusion on Cycle 1; 1, 2, 4, 8h post infusion on Cycle 2 (Cycle length =21 days)
measure: Part 1 (Safety Run-in): Plasma Cisplatin Concentration
timeFrame: Predose (0 h) and end of infusion on Cycle 1 and 2; 2, 4, 8 h post infusion on Cycle 1; 1.5, 2, 4, 8 h post infusion on Cycle 2 (Cycle length =21 days)
measure: Part 2 (Double-blind, Randomized, Placebo-controlled): Plasma Cisplatin Concentration
timeFrame: Predose (0 h) and end of infusion on Cycle 1 and 2; 2, 4, 8 h post infusion on Cycle 1; 1.5, 2, 4, 8 h post infusion on Cycle 2 (Cycle length = 21 days)
measure: Part 1 (Safety Run-in): Plasma Carboplatin Concentration
timeFrame: Predose (0 h), end of infusion, 1, 2, 4, 8 h post infusion on Cycles 1 and 2 (Cycle length =21 days)
measure: Part 2 (Double-blind, Randomized, Placebo-controlled): Plasma Carboplatin Concentration
timeFrame: Predose (0 h), end of infusion, 1, 2, 4, 8 h post infusion on Cycles 1 and 2 (Cycle length =21 days)
measure: Part 1 (Safety Run-in): Plasma Paclitaxel Concentration
timeFrame: Predose (0 h) and end of infusion on Cycle 1 and 2; 4, 8, 12 h post infusion on Cycle 1; 4, 6, 8, 12 h post infusion on Cycle 2 (Cycle length =21 days)
measure: Part 2 (Double-blind, Randomized, Placebo-controlled): Plasma Paclitaxel Concentration
timeFrame: Predose (0 h) and end of infusion on Cycle 1 and 2; 4, 8, 12 h post infusion on Cycle 1; 4, 6, 8, 12 h post infusion on Cycle 2 (Cycle length =21 days)
measure: Part 2 (Double-blind, Randomized, Placebo-controlled): Plasma Nab-paclitaxel Concentration
timeFrame: Predose (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)
measure: Part 2 (Double-blind, Randomized, Placebo-controlled): Time to Definitive 10-point Deterioration (TTDD) Symptom Scores of Pain, Cough and Dyspnea Per EORTC QLQ-LC13 Questionnaire
timeFrame: Up to approximately 25 months
measure: Part 2 (Double-blind, Randomized, Placebo-controlled): Time to Definitive Deterioration in Global Health Status/Quality of Life, Shortness of Breath and Pain Per EORTC QLQ-C30 Questionnaire
timeFrame: Up to approximately 25 months
measure: Part 2 (Double-blind, Randomized, Placebo-controlled): Change From Baseline in Score as Per the EuroQol 5 Dimension 5 Level (EQ-5D-5L) Questionnaire
timeFrame: Assessed every 3 weeks from Week 3 through Week 108, at follow-up visits 1, 2, 3, 4, and 5 (follow-up visits occurred every 26 days from week 108), and at 7 and 28 days post-disease progression, all up to a maximum of 3.5 years
measure: Part 2 (Double-blind, Randomized, Placebo-controlled): Change From Baseline in Score as Per the EuroQol 5 Dimension 5 Level (EQ-5D-5L) Questionnaire - Visual Analog Scale (VAS)
timeFrame: Assessed every 3 weeks from Week 3 through Week 108, at follow-up visits 1, 2, 3, 4, and 5 (follow-up visits occurred every 26 days from week 108), and at 7 and 28 days post-disease progression, all up to a maximum of 3.5 years
measure: All Collected Deaths
timeFrame: On-treatment deaths: Up to approximately 29 months in Part 1 or approximately 25 months in Part 2. Post-treatment survival follow-up deaths: Up to an additional 130 days.
Other outcomes:
Locations:
city: Long Beach
country: United States
facility: Pacific Shores Medical Group .
state: California
city: Los Angeles
country: United States
facility: USC Kenneth Norris Comprehensive Cancer Center .
state: California
city: Orlando
country: United States
facility: Advent Health Cancer Institute
state: Florida
city: Boston
country: United States
facility: Dana Farber Cancer Institute
state: Massachusetts
city: Caba
country: Argentina
facility: Novartis Investigative Site
state: Buenos Aires
city: Buenos Aires
country: Argentina
facility: Novartis Investigative Site
city: Westmead
country: Australia
facility: Novartis Investigative Site
state: New South Wales
city: Wooloongabba
country: Australia
facility: Novartis Investigative Site
state: Queensland
city: Melbourne
country: Australia
facility: Novartis Investigative Site
state: Victoria
city: Murdoch
country: Australia
facility: Novartis Investigative Site
state: Western Australia
city: Linz
country: Austria
facility: Novartis Investigative Site
state: Oberoesterreich
city: Salzburg
country: Austria
facility: Novartis Investigative Site
city: Barretos
country: Brazil
facility: Novartis Investigative Site
state: SP
city: Sao Paulo
country: Brazil
facility: Novartis Investigative Site
state: SP
city: Sao Paulo
country: Brazil
facility: Novartis Investigative Site
state: SP
city: Edmonton
country: Canada
facility: Novartis Investigative Site
state: Alberta
city: Brampton
country: Canada
facility: Novartis Investigative Site
state: Ontario
city: Toronto
country: Canada
facility: Novartis Investigative Site
state: Ontario
city: Temuco
country: Chile
facility: Novartis Investigative Site
state: Region De La Araucania
city: Santiago
country: Chile
facility: Novartis Investigative Site
city: Harbin
country: China
facility: Novartis Investigative Site
state: Heilongjiang
city: Wuhan
country: China
facility: Novartis Investigative Site
state: Hubei
city: Wuhan
country: China
facility: Novartis Investigative Site
state: Hubei
city: Changsha
country: China
facility: Novartis Investigative Site
state: Hunan
city: Changchun
country: China
facility: Novartis Investigative Site
state: Jilin
city: XI An
country: China
facility: Novartis Investigative Site
state: Shanxi
city: Hangzhou
country: China
facility: Novartis Investigative Site
state: Zhejiang
city: Beijing
country: China
facility: Novartis Investigative Site
city: Valledupar
country: Colombia
facility: Novartis Investigative Site
state: Cesar
city: Brno
country: Czechia
facility: Novartis Investigative Site
state: Czech Republic
city: Brno Bohunice
country: Czechia
facility: Novartis Investigative Site
city: Ostrava Vitkovice
country: Czechia
facility: Novartis Investigative Site
city: Praha
country: Czechia
facility: Novartis Investigative Site
city: Herning
country: Denmark
facility: Novartis Investigative Site
city: Oulu
country: Finland
facility: Novartis Investigative Site
city: Marseille cedex 20
country: France
facility: Novartis Investigative Site
state: Bouches Du Rhone
city: Lyon
country: France
facility: Novartis Investigative Site
city: Montpellier
country: France
facility: Novartis Investigative Site
city: Nantes Cedex 1
country: France
facility: Novartis Investigative Site
city: Paris
country: France
facility: Novartis Investigative Site
city: Berlin
country: Germany
facility: Novartis Investigative Site
city: Dresden
country: Germany
facility: Novartis Investigative Site
city: Essen
country: Germany
facility: Novartis Investigative Site
city: Georgsmarienhuette
country: Germany
facility: Novartis Investigative Site
city: Gerlingen
country: Germany
facility: Novartis Investigative Site
city: Gottingen
country: Germany
facility: Novartis Investigative Site
city: Halle (Saale)
country: Germany
facility: Novartis Investigative Site
city: Heidelberg
country: Germany
facility: Novartis Investigative Site
city: Koeln
country: Germany
facility: Novartis Investigative Site
city: Koeln
country: Germany
facility: Novartis Investigative Site
city: Leipzig
country: Germany
facility: Novartis Investigative Site
city: Muenchen
country: Germany
facility: Novartis Investigative Site
city: Athens
country: Greece
facility: Novartis Investigative Site
state: GR
city: Athens
country: Greece
facility: Novartis Investigative Site
city: Kowloon
country: Hong Kong
facility: Novartis Investigative Site
city: Veszprem
country: Hungary
facility: Novartis Investigative Site
city: Reykjavik
country: Iceland
facility: Novartis Investigative Site
city: Hyderabad
country: India
facility: Novartis Investigative Site
state: Andhra Pradesh
city: Gurgaon
country: India
facility: Novartis Investigative Site
state: Haryana
city: Pune
country: India
facility: Novartis Investigative Site
state: Maharashtra
city: Jaipur
country: India
facility: Novartis Investigative Site
state: Rajasthan
city: Hyderabad
country: India
facility: Novartis Investigative Site
state: Telangana
city: Kolkata
country: India
facility: Novartis Investigative Site
state: West Bengal
city: Avellino
country: Italy
facility: Novartis Investigative Site
state: AV
city: Genova
country: Italy
facility: Novartis Investigative Site
state: GE
city: Milano
country: Italy
facility: Novartis Investigative Site
state: MI
city: Milano
country: Italy
facility: Novartis Investigative Site
state: MI
city: Milano
country: Italy
facility: Novartis Investigative Site
state: MI
city: Rozzano
country: Italy
facility: Novartis Investigative Site
state: MI
city: Modena
country: Italy
facility: Novartis Investigative Site
state: MO
city: Padova
country: Italy
facility: Novartis Investigative Site
state: PD
city: Perugia
country: Italy
facility: Novartis Investigative Site
state: PG
city: Parma
country: Italy
facility: Novartis Investigative Site
state: PR
city: Orbassano
country: Italy
facility: Novartis Investigative Site
state: TO
city: Nagoya
country: Japan
facility: Novartis Investigative Site
state: Aichi
city: Sapporo city
country: Japan
facility: Novartis Investigative Site
state: Hokkaido
city: Himeji
country: Japan
facility: Novartis Investigative Site
state: Hyogo
city: Yokohama-city
country: Japan
facility: Novartis Investigative Site
state: Kanagawa
city: Sakai
country: Japan
facility: Novartis Investigative Site
state: Osaka
city: Sunto Gun
country: Japan
facility: Novartis Investigative Site
state: Shizuoka
city: Chuo ku
country: Japan
facility: Novartis Investigative Site
state: Tokyo
city: Ube-city
country: Japan
facility: Novartis Investigative Site
state: Yamaguchi
city: Osaka
country: Japan
facility: Novartis Investigative Site
city: Gyeonggi do
country: Korea, Republic of
facility: Novartis Investigative Site
state: Korea
city: Seoul
country: Korea, Republic of
facility: Novartis Investigative Site
state: Seocho Gu
city: Seoul
country: Korea, Republic of
facility: Novartis Investigative Site
city: Seoul
country: Korea, Republic of
facility: Novartis Investigative Site
city: Seoul
country: Korea, Republic of
facility: Novartis Investigative Site
city: Ashrafieh
country: Lebanon
facility: Novartis Investigative Site
city: Saida
country: Lebanon
facility: Novartis Investigative Site
city: Kuantan
country: Malaysia
facility: Novartis Investigative Site
state: Pahang
city: Kuching
country: Malaysia
facility: Novartis Investigative Site
state: Sarawak
city: Kuala Lumpur
country: Malaysia
facility: Novartis Investigative Site
state: Wilayah Persekutuan
city: Kuala Lumpur
country: Malaysia
facility: Novartis Investigative Site
city: Groningen
country: Netherlands
facility: Novartis Investigative Site
city: Groningen
country: Netherlands
facility: Novartis Investigative Site
city: Drammen
country: Norway
facility: Novartis Investigative Site
city: Taguig City
country: Philippines
facility: Novartis Investigative Site
state: Metro Manila
city: Makati City
country: Philippines
facility: Novartis Investigative Site
city: Quezon
country: Philippines
facility: Novartis Investigative Site
city: San Juan City
country: Philippines
facility: Novartis Investigative Site
city: Gliwice
country: Poland
facility: Novartis Investigative Site
city: Poznan
country: Poland
facility: Novartis Investigative Site
city: Tomaszw Mazowiecki
country: Poland
facility: Novartis Investigative Site
city: Lisboa
country: Portugal
facility: Novartis Investigative Site
city: Porto
country: Portugal
facility: Novartis Investigative Site
city: Craiova
country: Romania
facility: Novartis Investigative Site
state: Dolj
city: Cluj-Napoca
country: Romania
facility: Novartis Investigative Site
city: Arkhangelsk
country: Russian Federation
facility: Novartis Investigative Site
city: Omsk
country: Russian Federation
facility: Novartis Investigative Site
city: Pushkin Saint Petersburg
country: Russian Federation
facility: Novartis Investigative Site
city: Saint Petersburg
country: Russian Federation
facility: Novartis Investigative Site
city: St Petersburg
country: Russian Federation
facility: Novartis Investigative Site
city: Singapore
country: Singapore
facility: Novartis Investigative Site
city: Singapore
country: Singapore
facility: Novartis Investigative Site
city: Singapore
country: Singapore
facility: Novartis Investigative Site
city: Bratislava
country: Slovakia
facility: Novartis Investigative Site
state: Slovak Republic
city: Partizanske
country: Slovakia
facility: Novartis Investigative Site
city: Granada
country: Spain
facility: Novartis Investigative Site
state: Andalucia
city: Malaga
country: Spain
facility: Novartis Investigative Site
state: Andalucia
city: Badalona
country: Spain
facility: Novartis Investigative Site
state: Catalunya
city: Barcelona
country: Spain
facility: Novartis Investigative Site
state: Catalunya
city: Barcelona
country: Spain
facility: Novartis Investigative Site
state: Catalunya
city: San Sebastian
country: Spain
facility: Novartis Investigative Site
state: Pais Vasco
city: Las Palmas de Gran Canaria
country: Spain
facility: Novartis Investigative Site
city: Madrid
country: Spain
facility: Novartis Investigative Site
city: Madrid
country: Spain
facility: Novartis Investigative Site
city: Madrid
country: Spain
facility: Novartis Investigative Site
city: Madrid
country: Spain
facility: Novartis Investigative Site
city: Valencia
country: Spain
facility: Novartis Investigative Site
city: Zaragoza
country: Spain
facility: Novartis Investigative Site
city: Stockholm
country: Sweden
facility: Novartis Investigative Site
city: Basel
country: Switzerland
facility: Novartis Investigative Site
city: Kaohsiung
country: Taiwan
facility: Novartis Investigative Site
city: Tainan
country: Taiwan
facility: Novartis Investigative Site
city: Taipei
country: Taiwan
facility: Novartis Investigative Site
city: Taipei
country: Taiwan
facility: Novartis Investigative Site
city: Taoyuan
country: Taiwan
facility: Novartis Investigative Site
city: Songkhla
country: Thailand
facility: Novartis Investigative Site
state: Hat Yai
city: Khon Kaen
country: Thailand
facility: Novartis Investigative Site
state: THA
city: Bangkok
country: Thailand
facility: Novartis Investigative Site
city: Bangkok
country: Thailand
facility: Novartis Investigative Site
city: Bangkok
country: Thailand
facility: Novartis Investigative Site
city: Ankara
country: Turkey
facility: Novartis Investigative Site
city: Ankara
country: Turkey
facility: Novartis Investigative Site
city: Edirne
country: Turkey
facility: Novartis Investigative Site
city: Istanbul
country: Turkey
facility: Novartis Investigative Site
city: High Heaton
country: United Kingdom
facility: Novartis Investigative Site
state: Newcastle Upon Tyne
city: London
country: United Kingdom
facility: Novartis Investigative Site
city: Manchester
country: United Kingdom
facility: Novartis Investigative Site
city: Plymouth
country: United Kingdom
facility: Novartis Investigative Site
city: Hanoi
country: Vietnam
facility: Novartis Investigative Site
Study officials:
affiliation: Novartis Pharmaceuticals
name: Novartis Pharmaceuticals
role: STUDY_DIRECTOR
References: