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

Non-small Cell Lung Cancer Clinical Trial

— CANOPY-1  

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)

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT03631199
• Other study ID #: CACZ885U2301
• Secondary ID: 2018-001547-32
• Status: Active, not recruiting
• Phase: Phase 3
• Start date: December 21, 2018
• Est. completion date: June 7, 2027

Study information

• Verified date: March 2024
• Source: Novartis
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This is 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 subjects. The study will assess primarily the safety and tolerability (safety run-in part) of pembrolizumab plus platinum-based doublet chemotherapy with canakinumab and then the efficacy (double-blind, randomized, placebo controlled part) of pembrolizumab plus platinum-based doublet chemotherapy with or without canakinumab.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 673
• Est. completion date: June 7, 2027
• Est. primary completion date: August 9, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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-1ß 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. Other protocol-defined inclusion/exclusion criteria may apply.

Related Conditions & MeSH terms

• Carcinoma, Non-Small-Cell Lung
• Lung Neoplasms
• Non-small Cell Lung Cancer

Intervention

Drug:
• canakinumab
canakinumab every 3 weeks (squamous and non-squamous)
• canakinumab matching placebo
canakinumab placebo every 3 weeks (squamous and non-squamous)
• pembrolizumab
200 mg every 3 weeks (squamous and non-squamous)
• carboplatin
Area Under the Curve (AUC) 5 mg/mL*min every 3 weeks (non-squamous) or AUC 6 mg/mL*min (squamous)
• cisplatin
75 mg/m2 every 3 weeks (non-squamous)
• paclitaxel
200 mg/m2 every 3 weeks (squamous)
• nab-paclitaxel
100 mg/m2 every 3 weeks (squamous)
• pemetrexed
500 mg/m2 every 3 weeks (non-squamous)

Locations

Country	Name	City	State
Argentina	Novartis Investigative Site	Buenos Aires
Argentina	Novartis Investigative Site	Caba	Buenos Aires
Australia	Novartis Investigative Site	Melbourne	Victoria
Australia	Novartis Investigative Site	Murdoch	Western Australia
Australia	Novartis Investigative Site	Westmead	New South Wales
Australia	Novartis Investigative Site	Wooloongabba	Queensland
Austria	Novartis Investigative Site	Linz	Oberoesterreich
Austria	Novartis Investigative Site	Salzburg
Brazil	Novartis Investigative Site	Barretos	SP
Brazil	Novartis Investigative Site	Sao Paulo	SP
Brazil	Novartis Investigative Site	Sao Paulo	SP
Canada	Novartis Investigative Site	Brampton	Ontario
Canada	Novartis Investigative Site	Edmonton	Alberta
Canada	Novartis Investigative Site	Toronto	Ontario
Chile	Novartis Investigative Site	Santiago
Chile	Novartis Investigative Site	Temuco	Region De La Araucania
China	Novartis Investigative Site	Beijing
China	Novartis Investigative Site	Changchun	Jilin
China	Novartis Investigative Site	Changsha	Hunan
China	Novartis Investigative Site	Hangzhou	Zhejiang
China	Novartis Investigative Site	Harbin	Heilongjiang
China	Novartis Investigative Site	Wuhan	Hubei
China	Novartis Investigative Site	Wuhan	Hubei
China	Novartis Investigative Site	XI An	Shanxi
Colombia	Novartis Investigative Site	Valledupar	Cesar
Czechia	Novartis Investigative Site	Brno	Czech Republic
Czechia	Novartis Investigative Site	Brno - Bohunice
Czechia	Novartis Investigative Site	Ostrava Vitkovice
Czechia	Novartis Investigative Site	Prague 2	Czech Republic
Denmark	Novartis Investigative Site	Herning
Finland	Novartis Investigative Site	Oulu
France	Novartis Investigative Site	Lyon
France	Novartis Investigative Site	Marseille cedex 20	Bouches Du Rhone
France	Novartis Investigative Site	Montpellier
France	Novartis Investigative Site	Paris
France	Novartis Investigative Site	Saint Herblain
Germany	Novartis Investigative Site	Berlin
Germany	Novartis Investigative Site	Dresden
Germany	Novartis Investigative Site	Essen
Germany	Novartis Investigative Site	Georgsmarienhuette
Germany	Novartis Investigative Site	Gerlingen
Germany	Novartis Investigative Site	Gottingen
Germany	Novartis Investigative Site	Halle (Saale)
Germany	Novartis Investigative Site	Heidelberg
Germany	Novartis Investigative Site	Koeln
Germany	Novartis Investigative Site	Koeln
Germany	Novartis Investigative Site	Leipzig
Germany	Novartis Investigative Site	Muenchen
Greece	Novartis Investigative Site	Athens	GR
Greece	Novartis Investigative Site	Athens
Hong Kong	Novartis Investigative Site	Kowloon
Hungary	Novartis Investigative Site	Veszprem
Iceland	Novartis Investigative Site	Reykjavik
India	Novartis Investigative Site	Gurgaon	Haryana
India	Novartis Investigative Site	Hyderabad	Telangana
India	Novartis Investigative Site	Hyderabad	Andhra Pradesh
India	Novartis Investigative Site	Jaipur	Rajasthan
India	Novartis Investigative Site	Kolkata	West Bengal
India	Novartis Investigative Site	Pune	Maharashtra
Italy	Novartis Investigative Site	Avellino	AV
Italy	Novartis Investigative Site	Genova	GE
Italy	Novartis Investigative Site	Milano	MI
Italy	Novartis Investigative Site	Milano	MI
Italy	Novartis Investigative Site	Milano	MI
Italy	Novartis Investigative Site	Modena	MO
Italy	Novartis Investigative Site	Orbassano	TO
Italy	Novartis Investigative Site	Padova	PD
Italy	Novartis Investigative Site	Parma	PR
Italy	Novartis Investigative Site	Perugia	PG
Italy	Novartis Investigative Site	Rozzano	MI
Japan	Novartis Investigative Site	Chuo ku	Tokyo
Japan	Novartis Investigative Site	Himeji	Hyogo
Japan	Novartis Investigative Site	Nagoya	Aichi
Japan	Novartis Investigative Site	Osaka
Japan	Novartis Investigative Site	Sakai	Osaka
Japan	Novartis Investigative Site	Sapporo city	Hokkaido
Japan	Novartis Investigative Site	Sunto Gun	Shizuoka
Japan	Novartis Investigative Site	Ube-city	Yamaguchi
Japan	Novartis Investigative Site	Yokohama-city	Kanagawa
Korea, Republic of	Novartis Investigative Site	Gyeonggi do	Korea
Korea, Republic of	Novartis Investigative Site	Seoul	Seocho Gu
Korea, Republic of	Novartis Investigative Site	Seoul
Korea, Republic of	Novartis Investigative Site	Seoul
Korea, Republic of	Novartis Investigative Site	Seoul
Lebanon	Novartis Investigative Site	Ashrafieh
Lebanon	Novartis Investigative Site	Saida
Malaysia	Novartis Investigative Site	Kuala Lumpur	Wilayah Persekutuan
Malaysia	Novartis Investigative Site	Kuala Lumpur
Malaysia	Novartis Investigative Site	Kuantan	Pahang
Malaysia	Novartis Investigative Site	Kuching	Sarawak
Netherlands	Novartis Investigative Site	Groningen
Netherlands	Novartis Investigative Site	Groningen
Norway	Novartis Investigative Site	Drammen
Philippines	Novartis Investigative Site	Makati City
Philippines	Novartis Investigative Site	Quezon
Philippines	Novartis Investigative Site	San Juan City
Philippines	Novartis Investigative Site	Taguig City	Metro Manila
Poland	Novartis Investigative Site	Gliwice
Poland	Novartis Investigative Site	Poznan
Poland	Novartis Investigative Site	Tomaszw Mazowiecki
Portugal	Novartis Investigative Site	Lisboa
Portugal	Novartis Investigative Site	Porto
Romania	Novartis Investigative Site	Cluj-Napoca
Romania	Novartis Investigative Site	Craiova	Dolj
Russian Federation	Novartis Investigative Site	Arkhangelsk
Russian Federation	Novartis Investigative Site	Omsk
Russian Federation	Novartis Investigative Site	Pushkin Saint Petersburg
Russian Federation	Novartis Investigative Site	Saint Petersburg
Russian Federation	Novartis Investigative Site	St Petersburg
Singapore	Novartis Investigative Site	Singapore
Singapore	Novartis Investigative Site	Singapore
Singapore	Novartis Investigative Site	Singapore
Slovakia	Novartis Investigative Site	Bratislava
Slovakia	Novartis Investigative Site	Partizanske
Spain	Novartis Investigative Site	Badalona	Catalunya
Spain	Novartis Investigative Site	Barcelona	Catalunya
Spain	Novartis Investigative Site	Barcelona	Catalunya
Spain	Novartis Investigative Site	Granada	Andalucia
Spain	Novartis Investigative Site	Las Palmas De Gran Canarias
Spain	Novartis Investigative Site	Madrid
Spain	Novartis Investigative Site	Madrid
Spain	Novartis Investigative Site	Madrid
Spain	Novartis Investigative Site	Madrid
Spain	Novartis Investigative Site	Malaga	Andalucia
Spain	Novartis Investigative Site	San Sebastian	Pais Vasco
Spain	Novartis Investigative Site	Valencia
Spain	Novartis Investigative Site	Zaragoza
Sweden	Novartis Investigative Site	Stockholm
Switzerland	Novartis Investigative Site	Basel
Taiwan	Novartis Investigative Site	Kaohsiung
Taiwan	Novartis Investigative Site	Tainan
Taiwan	Novartis Investigative Site	Taipei
Taiwan	Novartis Investigative Site	Taipei
Taiwan	Novartis Investigative Site	Taoyuan
Thailand	Novartis Investigative Site	Bangkok
Thailand	Novartis Investigative Site	Bangkok
Thailand	Novartis Investigative Site	Bangkok
Thailand	Novartis Investigative Site	Khon Kaen	THA
Thailand	Novartis Investigative Site	Songkhla	Hat Yai
Turkey	Novartis Investigative Site	Ankara
Turkey	Novartis Investigative Site	Edirne
Turkey	Novartis Investigative Site	Istanbul
United Kingdom	Novartis Investigative Site	High Heaton	Newcastle Upon Tyne
United Kingdom	Novartis Investigative Site	London
United Kingdom	Novartis Investigative Site	Manchester
United Kingdom	Novartis Investigative Site	Plymouth
United States	Dana Farber Cancer Institute	Boston	Massachusetts
United States	Pacific Shores Medical Group .	Long Beach	California
United States	USC Kenneth Norris Comprehensive Cancer Center .	Los Angeles	California
United States	Advent Health Cancer Institute	Orlando	Florida
Vietnam	Novartis Investigative Site	Hanoi

Sponsors (1)

Lead Sponsor	Collaborator
Novartis Pharmaceuticals

Countries where clinical trial is conducted

United States,  Vietnam,  Argentina,  Australia,  Austria,  Brazil,  Canada,  Chile,  China,  Colombia,  Czechia,  Denmark,  Finland,  France,  Germany,  Greece,  Hong Kong,  Hungary,  Iceland,  India,  Italy,  Japan,  Korea, Republic of,  Lebanon,  Malaysia,  Netherlands,  Norway,  Philippines,  Poland,  Portugal,  Romania,  Russian Federation,  Singapore,  Slovakia,  Spain,  Sweden,  Switzerland,  Taiwan,  Thailand,  Turkey,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Safety run-in part: Incidence of dose limiting toxicities (DLTs)	Incidence of DLTs assessed among at least 6 evaluable subjects during the first 42 days of study treatment	6 months from start of safety run-in part
Primary	Double-blind, randomized, placebo-controlled part: Progression free survival (PFS) per investigator assessment using RECIST v1.1	Progression free survival is 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	18 months from start of randomization part
Primary	Double-blind, randomized, placebo-controlled part: 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	38 months from start of randomization part
Secondary	Safety run-in part: Overall response rate (ORR) per investigator assessment using RECIST v1.1	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	Baseline, every 6 weeks (for the first 12 weeks), then every 9 weeks (for the next 21 weeks) and every 12 weeks thereafter until progression per investigator assessment and up to 6 months
Secondary	Double-blind, randomized, placebo-controlled part : Overall response rate (ORR) per investigator assessment using RECIST v1.1	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	Baseline, every 6 weeks (for the first 12 weeks), then every 9 weeks (for the next 21 weeks) and every 12 weeks thereafter until progression per investigator assessment and up to 18 months
Secondary	Safety run-in part: Disease control rate (DCR) per investigator assessment using RECIST v1.1	Disease control rate is defined as the proportion of patients with complete response (CR) or partial response (PR) or subjects with stable disease (SD) as per investigator assessment according to RECIST 1.1 criteria	Baseline, every 6 weeks (for the first 12 weeks), then every 9 weeks (for the next 21 weeks) and every 12 weeks thereafter until progression per investigator assessment and up to 6 months
Secondary	Double-blind, randomized, placebo-controlled part : Disease control rate (DCR) per investigator assessment using RECIST v1.1	Disease control rate is defined as the proportion of patients with complete response (CR) or partial response (PR) or subjects with stable disease (SD) as per investigator assessment according to RECIST 1.1 criteria	Baseline, every 6 weeks (for the first 12 weeks), then every 9 weeks (for the next 21 weeks) and every 12 weeks thereafter until progression per investigator assessment and up to 18 months
Secondary	Safety run-in part: Duration of response (DOR) per investigator assessment using RECIST v1.1	Duration of response is defined as the time from first documented response of CR or PR to date of first documented progression or death due to any cause, according to RECIST 1.1 criteria	Baseline, every 6 weeks (for the first 12 weeks), then every 9 weeks (for the next 21 weeks) and every 12 weeks thereafter until progression per investigator assessment and up to 6 months
Secondary	Double-blind, randomized, placebo-controlled part : Duration of response (DOR) per investigator assessment using RECIST v1.1	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	Baseline, every 6 weeks (for the first 12 weeks), then every 9 weeks (for the next 21 weeks) and every 12 weeks thereafter until progression per investigator assessment and up to 18 months
Secondary	Double-blind, randomized, placebo-controlled part only: Time to response (TTR) per investigator assessment using RECIST v1.1	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	Baseline, every 6 weeks (for the first 12 weeks), then every 9 weeks (for the next 21 weeks) and every 12 weeks thereafter until progression per investigator assessment and up to 18 months
Secondary	Safety run-in part: Antidrug antibodies (ADA) of canakinumab		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
Secondary	Double-blind, randomized, placebo-controlled part : Antidrug antibodies (ADA) of canakinumab		Predose (0 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
Secondary	Safety run-in part: Antidrug antibodies (ADA) of pembrolizumab		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
Secondary	Double-blind, randomized, placebo-controlled part : Antidrug antibodies (ADA) of pembrolizumab		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
Secondary	Safety run-in part: Serum canakinumab concentration		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)
Secondary	Double-blind, randomized, placebo-controlled part : Serum canakinumab concentration		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)
Secondary	Safety run-in part: Serum pembrolizumab concentration		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)
Secondary	Double-blind, randomized, placebo-controlled part : Serum pembrolizumab concentration		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)
Secondary	Safety run-in part: Plasma pemetrexed concentration		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)
Secondary	Double-blind, randomized, placebo-controlled part : : Plasma pemetrexed concentration		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)
Secondary	Safety run-in part: Plasma cisplatin concentration		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)
Secondary	Double-blind, randomized, placebo-controlled part: Plasma cisplatin concentration		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)
Secondary	Safety run-in part: Plasma carboplatin concentration		Predose (0 h), end of infusion, 1, 2, 4, 8 h post infusion on Cycles 1 and 2 (Cycle length =21 days)
Secondary	Double-blind, randomized, placebo-controlled part: Plasma carboplatin concentration		Predose (0 h), end of infusion, 1, 2, 4, 8 h post infusion on Cycles 1 and 2 (Cycle length =21 days)
Secondary	Safety run-in part: Plasma paclitaxel concentration		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)
Secondary	Double-blind, randomized, placebo-controlled part: Plasma paclitaxel concentration		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)
Secondary	Double-blind, randomized, placebo-controlled part: Plasma nab-paclitaxel concentration		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)
Secondary	Double-blind, randomized, placebo-controlled part only :Time to definitive 10 point deterioration symptom scores of pain, cough and dyspnea per EORTC QLQ-LC13 questionnaire	To assess the effect of canakinumab vs placebo on time to onset or deterioration of lung cancer specific symptoms using the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Lung Cancer 13 (EORTC QLQ-LC13)	Baseline and at day 1 of every visit (with dosing or not) until end of treatment, before each tumor assessments and 2 times (7 days and 28 days) after disease progression and up to 18 months
Secondary	Double-blind, randomized, placebo-controlled part only: Time to definitive deterioration in global health status/quality of life, shortness of breath and pain per EORTC QLQ-C30 questionnaire	To assess the effect of canakinumab vs placebo on time to onset or deterioration of lung cancer specific symptoms using the European Organization for Research and Treatment Quality of Life Questionnaire core 30 (EORTC QLQ-C30)	Baseline and at day 1 of every visit (with dosing or not) until end of treatment, before each tumor assessments and 2 times (7 days and 28 days) after disease progression and up to 18 months
Secondary	Double-blind, randomized, placebo-controlled part only: change from baseline in score as per the EuroQol 5 Dimension 5 Level (EQ-5D-5L) questionnaire	To assess the effect of canakinumab versus placebo on patient reported outcomes ((PROs) - patient's health related quality of life)	Baseline and at day 1 of every visit (with dosing or not) until end of treatment, before each tumor assessments and 2 times (7 days and 28 days) after disease progression and up to 18 months