Clinical trial NCT03626545: Phase III Study Evaluating Efficacy and Safety of Canakinumab in Combination With Docetaxel in Adult Subjects With Non-small Cell Lung Cancers as a Second or Third Line Therapy
Official title: A Randomized, Double-blind, Placebo-controlled, Phase III Study Evaluating the Efficacy and Safety of Canakinumab in Combination With Docetaxel Versus Placebo in Combination With Docetaxel in Adult Subjects With Non-small Cell Lung Cancer (NSCLC) Previously Treated With PD-(L)1 Inhibitors and Platinum-based Chemotherapy (CANOPY 2)
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE3
Conditions: Non-Small-Cell Lung
Keywords: ACZ885
canakinumab
docetaxel
NSCLC
Non Small Cell Lung Cancer
Carcinoma
IL-1β
PD-(L)1
CANOPY
CANOPY-2
second or third line therapy
PD-(L)1 inhibitors
platinum-based chemotherapy
Lead sponsor: Novartis
Sponsor class: INDUSTRY
First posted: 2018-08-13
Enrollment: 245
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 study was designed to evaluate the role of canakinumab in combination with docetaxel in subjects with advanced non-small cell lung cancer (NSCLC) previously treated with PD-(L)1 inhibitors and platinum-based chemotherapy.

Detailed description: This was a multicenter, Phase III study designed to evaluate the efficacy and safety of canakinumab in combination with docetaxel versus placebo in combination with docetaxel, as second- or third-line treatment. The study included adult subjects with advanced NSCLC whose disease had progressed after prior treatment with a PD-(L)1 inhibitor. Subjects had also been pre-treated with platinum-based chemotherapy, either given together with PD-(L)1 inhibitor or sequentially.

The study consisted of 2 parts:

* Part 1: Safety run-in. This part was conducted to confirm the Recommended Phase 3 Regimen (RP3R) of the canakinumab and docetaxel combination. Participants were treated for at least 2 complete cycles of treatment (21 days per cycle) for safety evaluation (DLT-Dose Limiting Toxicities) to define RP3R. Participants from the safety run-in part were treated until any discontinuation criteria were met. After treatment discontinuation, all participants were followed for safety evaluations during the safety follow up period (up to 130 days). Additionally, subjects who discontinued study treatment without prior documented disease progression continued efficacy assessments in the efficacy follow-up phase irrespective of the start of new antineoplastic therapy and until documented progressive disease as per protocol. After the RP3R was determined, enrollment in this part was closed and additional participants were enrolled in the randomized part (part 2) of the study. Ongoing patients from the safety run-in part continued their treatment at the assigned dose level according to the dose and schedule for the safety run-in part.
* Part 2: Randomized part. The randomized, double-blind, placebo-controlled part of the study opened after confirmation of the RP3R for the combination of canakinumab and docetaxel. Participants from the randomized part were treated until any discontinuation criteria were met as per protocol. After treatment discontinuation, all participants were followed for safety evaluations during the safety follow up period (up to 130 days). Additionally, subjects who discontinued study treatment without prior documented disease progression continued efficacy assessments in the efficacy follow-up phase irrespective of the start of new antineoplastic therapy and until documented progressive disease as per protocol.

Based on the lack of efficacy observed in the primary analysis, Novartis decided to halt canakinumab/placebo treatment. Subjects continued to receive docetaxel if they were deriving clinical benefit as per investigator assessment until discontinuation

Eligibility criteria: Key Inclusion Criteria:

* Histologically confirmed advanced (stage IIIB) or metastatic NSCLC.
* Subject had received one prior platinum-based chemotherapy and one prior PD-(L)1 inhibitor therapy for locally advanced or metastatic disease.
* Subject with ECOG performance status (PS) of 0 or 1.
* Subject with at least 1 evaluable (measurable or non-measurable) lesion by RECIST 1.1 in solid tumors criteria.

Key Exclusion Criteria:

* Subject who previously received docetaxel, canakinumab (or another IL-1β inhibitor), or any systemic therapy for their locally advanced or metastatic NSCLC other than one platinum-based chemotherapy and one prior PD-(L)1 inhibitor.
* Subject with EGFRor ALK positive tumor.
* History of severe hypersensitivity reaction to monoclonal antibodies, taxanes or excipients of docetaxel or canakinumab.

Primary outcomes:
measure: Safety run-in Part: Percentage of Participants With Dose Limiting Toxicities (DLTs)
timeFrame: During the first 42 days of dosing
measure: Randomized Part: Overall Survival (OS)
timeFrame: From randomization until death or final analysis data cutoff date (08-Jan-2021) whichever comes first (up to approximately (approx.) 18 months)
Secondary outcomes:
measure: Overall Response Rate (ORR)
timeFrame: Through final analysis data cutoff date of 08-Jan-2021 (assessed up to approx. 10 months for the safety run-in part and 18 months for the randomized part)
measure: Duration of Response (DOR)
timeFrame: From first documented response of CR or PR to date of first documented progression, death or final analysis data cutoff date (08-Jan-2021) whichever comes first (up to approx. 10 months for the safety run-in and 18 months for the randomized)
measure: Disease Control Rate (DCR)
timeFrame: Through final analysis data cutoff date of 08-Jan-2021 (assessed up to approx. 10 months for the safety run-in part and 18 months for the randomized part)
measure: Randomized Part: Progression-Free Survival (PFS)
timeFrame: From randomization until disease progression, death or final analysis data cutoff date (08-Jan-2021) whichever comes first (assessed up to approx. 18 months)
measure: Randomized Part: Time to Response (TTR)
timeFrame: From randomization until first documented response or final analysis data cutoff date (08-Jan-2021) whichever comes first (up to approx. 18 months)
measure: Randomized Part: Time to Definitive 10-point Deterioration (TTD) Symptom Scores of Chest Pain, Cough and Dyspnea Per European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ) Lung Cancer (LC13) Questionnaire
timeFrame: From baseline through final analysis data cutoff date of 08-Jan-2021 (assessed up to approx. 18 months)
measure: Randomized Part: Time to Definitive 10-point Deterioration in Global Health Status (GHS)/Quality of Life (QoL), Shortness of Breath and Pain Per EORTC QLQ-C30 Questionnaire
timeFrame: From baseline through final analysis data cutoff date of 08-Jan-2021 (assessed up to approx. 18 months)
measure: Randomized Part: Change From Baseline in GHS/QoL, Shortness of Breath and Pain Scores as Per the EORTC QLQ C30 Questionnaire
timeFrame: Baseline, every 3 weeks from Week 3 until end of treatment, every 6 or 12 weeks post-treatment until progression (post-treatment efficacy visits), 7 and 28 days post progression through final analysis cutoff date of 08Jan2021 (up to approx. 18 months)
measure: Randomized Part: Change From Baseline in Chest Pain, Cough and Dyspnea Scores as Per the EORTC-QLQ LC13 Questionnaire
timeFrame: Baseline, every 3 weeks from Week 3 until end of treatment, every 6 or 12 weeks post-treatment until progression (post-treatment efficacy visits), 7 and 28 days post progression through final analysis cutoff date of 08Jan2021 (up to approx. 18 months)
measure: Randomized Part: Change From Baseline in European Quality of Life-5 Dimensions-5 Level (EQ-5D-5L) Health State Scores
timeFrame: Baseline, every 3 weeks from Week 3 until end of treatment, every 6 or 12 weeks post-treatment until progression (post-treatment efficacy visits), 7 and 28 days post progression through final analysis cutoff date of 08Jan2021 (up to approx. 18 months)
measure: Safety run-in Part: Maximum Plasma Concentration (Cmax) of Canakinumab
timeFrame: Cycle 1 Day 1 at pre-dose and end of infusion and 24, 48, 168 and 336 hours (h) post-infusion. Each cycle is 21 days
measure: Safety run-in Part: Time of Maximum Plasma Concentration (Tmax) of Canakinumab
timeFrame: Cycle 1 Day 1 at pre-dose and end of infusion and 24, 48, 168 and 336 hours (h) post-infusion. Each cycle is 21 days
measure: Safety run-in Part: Area Under the Plasma Concentration-time Curve From Time Zero to the Last Quantifiable Concentration (AUClast) of Canakinumab
timeFrame: Cycle 1 Day 1 at pre-dose and end of infusion and 24, 48, 168 and 336 hours (h) post-infusion. Each cycle is 21 days
measure: Safety run-in Part: Cmax of Docetaxel
timeFrame: Cycle 1 Day 1 and Cycle 2 Day 1 at pre-infusion, end of infusion, and 2, 4, 6 and 8 hours post-dose. Each cycle is 21 days
measure: Safety run-in Part: Tmax of Docetaxel
timeFrame: Cycle 1 Day 1 and Cycle 2 Day 1 at pre-infusion, end of infusion, and 2, 4, 6 and 8 hours post-dose. Each cycle is 21 days
measure: Safety run-in Part: AUClast of Docetaxel
timeFrame: Cycle 1 Day 1 and Cycle 2 Day 1 at pre-infusion, end of infusion, and 2, 4, 6 and 8 hours post-dose. Each cycle is 21 days
measure: Randomized Part: Pre-dose Plasma Trough Concentration (CTrough) of Canakinumab
timeFrame: Pre-dose on Cycle 1 Day 1, Cycle 4 Day 1, Cycle 6 Day 1, Cycle 12 Day 1 and Cycle 18 Day 1. Each cycle is 21 days.
measure: Randomized Part: Cmax of Docetaxel
timeFrame: Cycle 1 Day 1 and Cycle 4 Day 1 at pre-infusion, end of infusion, and 2, 4 and 6 hours post-dose. Each cycle is 21 days
measure: Randomized Part: Tmax of Docetaxel
timeFrame: Cycle 1 Day 1 and Cycle 4 Day 1 at pre-infusion, end of infusion, and 2, 4 and 6 hours post-dose. Each cycle is 21 days
measure: Randomized Part: AUClast of Docetaxel
timeFrame: Cycle 1 Day 1 and Cycle 4 Day 1 at pre-infusion, end of infusion, and 2, 4 and 6 hours post-dose. Each cycle is 21 days
measure: Randomized Part: Canakinumab Antidrug Antibodies (ADA) at Baseline
timeFrame: Baseline
measure: Randomized Part: Canakinumab ADA Incidence On-treatment
timeFrame: Pre-dose at Cycle 1 Day 1, Cycle 4 Day 1, Cycle 6 Day 1, Cycle 12 Day 1 , end of treatment, and 130 days after end of treatment through final analysis data cutoff date of 08-Jan-2021 (assessed up to 18 months). Each cycle is 21 days
Other outcomes:
Locations:
city: Atlanta
country: United States
facility: Emory Winship Cancer Institute
state: Georgia
city: Kansas City
country: United States
facility: Saint Luke's Hospital/Marion Bloch Neuroscience Institute Dept of Regulatory
state: Missouri
city: Bronx
country: United States
facility: Montefiore Medical Center Albert Einstein College of Med
state: New York
city: Cincinnati
country: United States
facility: University of Cincinnati Cancer Institute
state: Ohio
city: Houston
country: United States
facility: MD Anderson
state: Texas
city: Salt Lake City
country: United States
facility: Huntsman Cancer Institute Univ of Utah .
state: Utah
city: Berazategui
country: Argentina
facility: Novartis Investigative Site
state: Buenos Aires
city: Caba
country: Argentina
facility: Novartis Investigative Site
state: Buenos Aires
city: Mar del Plata
country: Argentina
facility: Novartis Investigative Site
state: Buenos Aires
city: La Rioja
country: Argentina
facility: Novartis Investigative Site
city: Santiago del Estero
country: Argentina
facility: Novartis Investigative Site
city: Greenslopes
country: Australia
facility: Novartis Investigative Site
state: Queensland
city: Shepparton
country: Australia
facility: Novartis Investigative Site
state: Victoria
city: Sint Niklaas
country: Belgium
facility: Novartis Investigative Site
state: Oost Vlaanderen
city: Bruxelles
country: Belgium
facility: Novartis Investigative Site
city: Charleroi
country: Belgium
facility: Novartis Investigative Site
city: Gent
country: Belgium
facility: Novartis Investigative Site
city: Roeselare
country: Belgium
facility: Novartis Investigative Site
city: Salvador
country: Brazil
facility: Novartis Investigative Site
state: BA
city: Porto Alegre
country: Brazil
facility: Novartis Investigative Site
state: RS
city: Itajai
country: Brazil
facility: Novartis Investigative Site
state: SC
city: Vancouver
country: Canada
facility: Novartis Investigative Site
state: British Columbia
city: Montreal
country: Canada
facility: Novartis Investigative Site
state: Quebec
city: Santiago
country: Chile
facility: Novartis Investigative Site
city: Chengdu
country: China
facility: Novartis Investigative Site
state: Sichuan
city: Shanghai
country: China
facility: Novartis Investigative Site
city: Brno - Bohunice
country: Czechia
facility: Novartis Investigative Site
city: Ostrava Vitkovice
country: Czechia
facility: Novartis Investigative Site
city: Herlev
country: Denmark
facility: Novartis Investigative Site
city: Odense C
country: Denmark
facility: Novartis Investigative Site
city: Le Mans
country: France
facility: Novartis Investigative Site
state: Cedex 09
city: Besancon Cedex
country: France
facility: Novartis Investigative Site
city: Bordeaux Cedex
country: France
facility: Novartis Investigative Site
city: Bron
country: France
facility: Novartis Investigative Site
city: Strasbourg Cedex
country: France
facility: Novartis Investigative Site
city: Berlin
country: Germany
facility: Novartis Investigative Site
city: Dresden
country: Germany
facility: Novartis Investigative Site
city: Frankfurt
country: Germany
facility: Novartis Investigative Site
city: Gerlingen
country: Germany
facility: Novartis Investigative Site
city: Grosshansdorf
country: Germany
facility: Novartis Investigative Site
city: Koeln
country: Germany
facility: Novartis Investigative Site
city: Ulm
country: Germany
facility: Novartis Investigative Site
city: Heraklion Crete
country: Greece
facility: Novartis Investigative Site
city: Thessaloniki
country: Greece
facility: Novartis Investigative Site
city: Torokbalint
country: Hungary
facility: Novartis Investigative Site
state: Pest
city: Ramat Gan
country: Israel
facility: Novartis Investigative Site
city: Lucca
country: Italy
facility: Novartis Investigative Site
state: LU
city: Rozzano
country: Italy
facility: Novartis Investigative Site
state: MI
city: Aviano
country: Italy
facility: Novartis Investigative Site
state: PN
city: Nagoya
country: Japan
facility: Novartis Investigative Site
state: Aichi
city: Himeji
country: Japan
facility: Novartis Investigative Site
state: Hyogo
city: Yokohama-city
country: Japan
facility: Novartis Investigative Site
state: Kanagawa
city: Chuo ku
country: Japan
facility: Novartis Investigative Site
state: Tokyo
city: Osaka
country: Japan
facility: Novartis Investigative Site
city: Amman
country: Jordan
facility: Novartis Investigative Site
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: Ashrafieh
country: Lebanon
facility: Novartis Investigative Site
city: Amsterdam
country: Netherlands
facility: Novartis Investigative Site
city: Groningen
country: Netherlands
facility: Novartis Investigative Site
city: Maastricht
country: Netherlands
facility: Novartis Investigative Site
city: Gdansk
country: Poland
facility: Novartis Investigative Site
city: Rzeszow
country: Poland
facility: Novartis Investigative Site
city: Warszawa
country: Poland
facility: Novartis Investigative Site
city: Pushkin 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: Malaga
country: Spain
facility: Novartis Investigative Site
state: Andalucia
city: Badalona
country: Spain
facility: Novartis Investigative Site
state: Catalunya
city: Valencia
country: Spain
facility: Novartis Investigative Site
state: Comunidad Valenciana
city: La Coruna
country: Spain
facility: Novartis Investigative Site
state: Galicia
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: Tainan
country: Taiwan
facility: Novartis Investigative Site
city: Taipei
country: Taiwan
facility: Novartis Investigative Site
Study officials:
affiliation: Novartis Pharmaceuticals
name: Novartis Pharmaceuticals
role: STUDY_DIRECTOR
References: