Neoplasms

All Conditions

Respiratory Tract (Lung and Bronchial) Diseases

Carcinoma

Carcinoma, Non-Small-Cell Lung

Lung Neoplasms

Respiratory Tract Neoplasms

Thoracic Neoplasms

Lung Diseases

Respiratory Tract Diseases

Carcinoma, Bronchogenic

Bronchial Neoplasms

Antineoplastic Agents

All Drugs and Chemicals

Docetaxel

Tubulin Modulators

Antimitotic Agents

Participants were treated with full doses of docetaxel 75mg/m\^2 intravenous and canakinumab 200 mg subcutaneous on Day 1 of each 21-Day cycle (dose level 1). Subjects were assessed for at least 2 complete cycles of treatment (21 days per cycle; a total of 42 days) for safety evaluation (DLT) to define RP3R. De-escalation to canakinumab 200 mg subcutaneous every 6 weeks + docetaxel 75 mg/m\^2, every 3 weeks could also be considered.

Participants were treated with canakinumab subcutaneous at RP3R and docetaxel at 75 mg/m\^2 every 3 weeks

Participants were treated with placebo subcutaneous at RP3R and docetaxel at 75 mg/m\^2 every 3 weeks

Canakinumab, 200 mg, subcutaneous. The initial dose regimen was once every 3 weeks (on Day 1 of each 21-day cycle)

Canakinumab

Docetaxel 75mg/m\^2, intravenous, administered on Day 1 of each 21-day cycle

Placebo, sub-cutaneous, admnistered at the RP3R defined in Part 1-safety run-in.

Placebo

Novartis Pharmaceuticals

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.

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

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

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)

Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent expert panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations.

This trial data is currently available according to the process described on www.clinicalstudydatarequest.com.

Percentage of participants with DLTs. A dose-limiting toxicity (DLT) is defined as an adverse event or abnormal laboratory value assessed as unrelated to disease, disease progression, inter-current illness, or concomitant medications that occurs within the first 42 days of docetaxel and canakinumab treatment.

OS is defined as the time from randomization to date of death due to any cause. The OS distribution was estimated using the Kaplan-Meier method and associated 95% confidence intervals were calculated for each treatment group. If a subject was not known to have died, then OS was censored at the latest date the subject was known to be alive (on or before the cut-off date).

ORR is 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. The 95% confidence intervals (CIs) were computed using Clopper and Pearson method.

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.

DOR is defined as the time from first documented response of CR or PR to date of first documented progression or death, by investigator's assessment according to RECIST 1.1 criteria. The DOR distribution was estimated using the Kaplan-Meier method and associated 95% confidence intervals were calculated for each treatment group.

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.

DCR is defined as the percentage of participants with CR or PR or with stable disease (SD) as per investigator assessment according to RECIST 1.1 criteria. The 95% CIs were computed using Clopper and Pearson method.

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.

SD: Neither sufficient shrinkage to qualify for PR or CR nor an increase in lesions which would qualify for progressive disease.

PFS is defined as the time from randomization to the date of the first documented radiological progression by investigator assessment according to RECIST 1.1 response criteria or death due to any cause.

The PFS distribution was estimated using the Kaplan-Meier method and associated 95% confidence intervals were calculated for each treatment group. If a participant did not have disease progression or die at the analysis cut-off date, PFS was censored at the date of last adequate tumor assessment.

TTR is defined as the time from the date of randomization to the date of first documented response of either CR or PR, by investigator's assessment according to RECIST 1.1 criteria. The TTR distribution was estimated using the Kaplan-Meier method and associated 95% confidence intervals were calculated for each treatment group. Subjects without a confirmed CR or PR at the time of the analysis cut-off date were censored at the study-maximum follow-up time for subjects with a PFS event (i.e., disease progression or death due to any cause), or at the date of the last adequate tumor assessment for subjects without a PFS event.

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.

The EORTC QLQ-LC13 comprises both multi-item and single-item measures of lung cancer-associated symptoms (ie, coughing, dyspnea, and chest pain) and treatment-related symptoms from conventional chemotherapy and radiotherapy (ie. hair loss, neuropathy, sore mouth, and dysphagia). Scores for each scale and single-item range from 0 to 100, with higher scores indicating higher level of symptoms. TTD for chest pain, cough and dyspnea is defined as the time from randomization to the date of event, which is defined as at least 10 points absolute worsening from baseline of the corresponding scale score, with no later change below this threshold ie.\<10 points was observed or if this worsening was observed at the last assessment for the subject, or death due to any cause (whichever occurs earlier). If a subject did not have an event, TTD was censored at the last adequate assessment.

The EORTC QLQ-C30 includes 5 functional scales (physical,role,cognitive,emotional and social), 3 symptom scales (fatigue,pain and nausea/vomiting), a GHS/QoL scale, and 6 single items (constipation,diarrhea,insomnia,shortness of breath,appetite loss and financial difficulties). For each scale and single-item, scores range between 0 and 100. A high score for functional scales/ GHS/QoL represents better functioning or QoL, a high score for symptom scales/single items represents significant symptomatology. TTD in GHS/QoL, shortness of breath and pain is defined as the time from randomization to the date of event, defined as at least 10 points absolute worsening from baseline of the corresponding scale score, with no later change below this threshold i.e.\<10 points was observed or if this worsening was observed at the last assessment for the subject, or death due to any cause (whichever occurs earlier). If a subject did not have an event, TTD was censored at the last adequate assessment.

The EORTC QLQ-C30 includes 5 functional scales (physical, role, cognitive, emotional and social), 3 symptom scales (fatigue, pain and nausea/vomiting), a GHS/QoL scale, and 6 single items (constipation, diarrhea, insomnia, dyspnoea, appetite loss and financial difficulties). For each scale and item, scores range 0-100. A high score for functional scales/QoL represents better functioning/QoL; a high score for symptom scales and items represents significant symptomatology. Changes from baseline in QoL, shortness of breath and pain scores are presented. For QoL, a negative change from baseline indicates improvement; for shortness of breath and pain a positive change from baseline indicates improvement. For subjects who discontinued treatment without disease progression, post-treatment efficacy visits 1, 2, 3 and 5 were conducted every 6 weeks (for the first 12 months since start of treatment) and every 12 weeks (after 12 months since start of treatment) until disease progression

The EORTC QLQ-LC13 is a 13-item questionnaire. It comprises both multi-item and single-item measures of lung cancer-associated symptoms (ie, coughing, dyspnea, and chest pain) and treatment-related symptoms from conventional chemotherapy and radiotherapy (ie, hair loss, neuropathy, sore mouth, and dysphagia). Scores for each scale and single-item range from 0 to 100, with higher scores indicating higher ("worse") level of symptoms. Changes from baseline in chest pain, cough and dyspnea scores are presented. A positive change from baseline indicates improvement. For subjects who discontinued treatment without disease progression, post-treatment efficacy visits 1, 2, 3 and 5 were conducted every 6 weeks (for the first 12 months since start of treatment) and every 12 weeks (after 12 months since start of treatment) until disease progression

The EQ-5D-5L descriptive system provides a profile of the participant's health state in 5 dimensions (mobility, self-care, usual activities, pain/discomfort, and anxiety/depression). For each of these dimensions, the participant self-assigned a score: from 1 (no problems) to 5 (extreme problems). The 5 digit health states obtained for each dimension was converted into a single mean index value based on the EQ-5D crosswalk value set for the UK using the time trade-off method. This index ranges from -0.594 (worst health) to 1.0 (best health). A positive change from baseline indicates improvement. For subjects who discontinued treatment without disease progression, post-treatment efficacy visits 1, 2, 3 and 5 were conducted every 6 weeks (for the first 12 months since start of treatment) and every 12 weeks (after 12 months since start of treatment) until disease progression

Venous whole blood samples were collected for pharmacokinetics characterization. Cmax of canakinumab was calculated from canakinumab plasma concentration-time data using non-compartmental methods and summarized using descriptive statistics.

Venous whole blood samples were collected for pharmacokinetics characterization. Tmax of canakinumab was calculated from canakinumab plasma concentration-time data using non-compartmental methods and summarized using descriptive statistics.

Actual recorded sampling times were considered for the calculations.

Venous whole blood samples were collected for pharmacokinetics characterization. AUClast of canakinumab was calculated from canakinumab plasma concentration-time data using non-compartmental methods and summarized using descriptive statistics.

Venous whole blood samples were collected for pharmacokinetics characterization. Cmax of docetaxel was calculated from docetaxel plasma concentration-time data using non-compartmental methods and summarized using descriptive statistics.

Venous whole blood samples were collected for pharmacokinetics characterization. Tmax of docetaxel was calculated from docetaxel plasma concentration-time data using non-compartmental methods and summarized using descriptive statistics.

Actual recorded sampling times were considered for the calculations.

Venous whole blood samples were collected for pharmacokinetics characterization. AUClast of docetaxel was calculated from docetaxel plasma concentration-time data using non-compartmental methods and summarized using descriptive statistics.

Venous whole blood samples were collected for pharmacokinetics characterization. CTrough of canakinumab was calculated from canakinumab plasma concentration-time data using non-compartmental methods and summarized using descriptive statistics.

ADA prevalence at baseline was calculated as the percentage of participants who had an ADA positive result at baseline

ADA incidence on-treatment was calculated as the percentage of participants who were treatment-induced ADA positive (post-baseline ADA positive with ADA-negative sample at baseline) and treatment-boosted ADA positive (post-baseline ADA positive with titer that is at least the fold titer change greater than the ADA-positive baseline titer)

Treatment-emergent AEs refer to any signs or symptoms observed during the study treatment and up to 130 days after treatment, considering the Safety Set. This set includes all subjects who were assigned study treatment and received at least one dose, including incomplete infusions.

All-Cause Mortality analysis encompasses the Full Analysis Set, including all subjects who were assigned study treatment

Deaths were collected in the pre-treatment period (from day of patient's informed consent to the day before first administration of study treatment )

All Participants (Pre-treatment)

AEs during on-treatment period (up to 130 days post-treatment)

Safety run-in Part: Canakinumab+Docetaxel (On-treatment)

Deaths collected in the post- treatment follow-up period (starting from day 131 post- treatment). No AEs were collected during this period

Safety run-in Part: Canakinumab+Docetaxel (Post-treatment Follow-up)

AEs during on-treatment period (up to 30 days post-treatment)

Randomized Part: Canakinumab + Docetaxel (On-treatment)

Deaths collected in the post- treatment follow-up period (starting from day 131 post-treatment). No AEs were collected during this period

Randomized Part: Canakinumab + Docetaxel (Post-treatment Follow-up)

Randomized Part: Placebo + Docetaxel (On-treatment)

Randomized Part: Placebo + Docetaxel (Post-treatment Follow-up)

Participants were treated with full doses of docetaxel 75mg/m\^2 intravenous and canakinumab 200 mg subcutaneous on Day 1 of each 21-Day cycle (dose level 1).

Safety run-in Part: Canakinumab+Docetaxel

Participants were randomized to receive canakinumab subcutaneous at RP3R and docetaxel at 75 mg/m\^2 on Day 1 of each 21-Day cycle

Randomized Part: Canakinumab + Docetaxel

Participants were randomized to receive placebo subcutaneous at RP3R and docetaxel at 75 mg/m\^2 on Day 1 of each 21-Day cycle

Randomized Part: Placebo + Docetaxel

Total

Age, Continuous

Sex: Female, Male

Race/Ethnicity, Customized

Study director

Participants in the safety run-in part to whom study treatment was assigned, who received at least one dose of any study treatment (including incomplete infusion) and met the minimum exposure criterion and have sufficient safety evaluations, or experienced a DLT during the first 42 days of dosing

Safety run-in Part: Percentage of Participants With Dose Limiting Toxicities (DLTs)

Full Analysis Set (FAS) in randomized part: All participants to whom study treatment was assigned by randomization.

Randomized Part: Overall Survival (OS)

FAS in Safety run-in part: all participants to whom study treatment was assigned and who received at least one dose of any study treatment (including incomplete infusion) FAS in Randomized part: all participants to whom study treatment was assigned by randomization

Overall Response Rate (ORR)

FAS in Safety run-in part: all participants to whom study treatment was assigned and who received at least one dose of any study treatment (including incomplete infusion) for whom best overall response is CR or PR FAS in Randomized part: all participants to whom study treatment was assigned by randomization for whom best overall response is CR or PR

Duration of Response (DOR)

Disease Control Rate (DCR)

FAS in Randomized part: All participants to whom study treatment was assigned by randomization

Randomized Part: Progression-Free Survival (PFS)

Randomized Part: Time to Response (TTR)

Chest Pain

Cough

Dyspnea

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

GHS/QOL

Shortness of breath

Pain

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

GHS/QoL: Week 3

GHS/QoL: Week 6

GHS/QoL: Week 9

GHS/QoL: Week 12

GHS/QoL: Week 15

GHS/QoL: Week 18

GHS/QoL: Week 21

GHS/QoL: Week 24

GHS/QoL: Week 27

GHS/QoL: Week 30

GHS/QoL: Week 33

GHS/QoL: Week 36

GHS/QoL: Week 39

GHS/QoL: Week 42

GHS/QoL: Week 45

GHS/QoL: Week 48

GHS/QoL: Week 51

GHS/QoL: Week 54

GHS/QoL: Week 57

GHS/QoL: Week 60

GHS/QoL: Week 63

GHS/QoL: Week 66

GHS/QoL: Week 69

GHS/QoL: Week 72

GHS/QoL: Week 75

GHS/QoL: Week 78

GHS/QoL: post treatment efficacy visit 1

GHS/QoL: post treatment efficacy visit 2

GHS/QoL: post treatment efficacy visit 3

GHS/QoL: post treatment efficacy visit 5

GHS/QoL: 7 days post disease progression

GHS/QoL: 28 days post disease progression

Shortness of breath: Week 3

Shortness of breath: Week 6

Shortness of breath: Week 9

Shortness of breath: Week 12

Shortness of breath: Week 15

Shortness of breath: Week 18

Shortness of breath: Week 21

Shortness of breath: Week 24

Shortness of breath: Week 27

Shortness of breath: Week 30

Shortness of breath: Week 33

Shortness of breath: Week 36

Shortness of breath: Week 39

Shortness of breath: Week 42

Shortness of breath: Week 45

Shortness of breath: Week 48

Shortness of breath: Week 51

Shortness of breath: Week 54

Shortness of breath: Week 57

Shortness of breath: Week 60

Shortness of breath: Week 63

Shortness of breath: Week 66

Shortness of breath: Week 69

Shortness of breath: Week 72

Shortness of breath: Week 75

Shortness of breath: Week 78

Shortness of breath: post treatment efficacy visit 1

Shortness of breath: post treatment efficacy visit 2

Shortness of breath: post treatment efficacy visit 3

Shortness of breath: post treatment efficacy visit 5

Shortness of breath: 7 days post disease progression

Shortness of breath: 28 days post disease progression

Pain: Week 3

Pain: Week 6

Pain: Week 9

Pain: Week 12

Pain: Week 15

Pain: Week 18

Pain: Week 21

Pain: Week 24

Pain: Week 27

Pain: Week 30

Pain: Week 33

Pain: Week 36

Pain: Week 39

Pain: Week 42

Pain: Week 45

Pain: Week 48

Pain: Week 51

Pain: Week 54

Pain: Week 57

Pain: Week 60

Pain: Week 63

Pain: Week 66

Pain: Week 69

Pain: Week 72

Pain: Week 75

Pain: Week 78

Pain: post treatment efficacy visit 1

Pain: post treatment efficacy visit 2

Pain: post treatment efficacy visit 3

Pain: post treatment efficacy visit 5

Pain: 7 days post disease progression

Pain: 28 days post disease progression

FAS in Randomized part: All participants to whom study treatment was assigned by randomization. Number analyzed represents participants with data available at the specified data points

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
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	NCT03626545	Non-Small-Cell ...	Canakinumab Docetaxel Placebo	18 Years -	Novartis
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	NCT03626545	Non-Small-Cell ...	Canakinumab Docetaxel Placebo	18 Years -	Novartis

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