stages AJCC v. 8 IIIB (not eligible for definite chemoradiation therapy) or stage IV (metastatic) non-small cell lung cancer (NSCLC) MedDRA version: 20.0 Level: PT Classification code 10061873 Term: Non-small cell lung cancer System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Sponsors
Novartis Farmacéutica, S.A.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Histologically confirmed locally advanced or metastatic NSCLC 2. Measurable disease by RECIST 1.1 3. Known PD-L1 status 4. ECOG performance status (PS) = 1. 5. Other protocol-defined inclusion criteria may apply. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 314 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 313
Exclusion criteria
Exclusion criteria: 1. Previous immunotherapy or treatment with IL-1ß inhibitor. 2. Subjects with epidermal growth factor receptor (EGFR) sensitizing mutations and/or ALK rearrangement 3. History of severe hypersensitivity reaction to monoclonal antibodies, platinum containing drugs, nab-paclitaxel, paclitaxel, pemetrexed or any known excipients of these drugs 4. Other protocol-defined exclusion criteria may apply.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Safety run-in part: To determine the recommended phase 3 dose regimen (RP3R) of canakinumab in combination with pembrolizumab plus platinum-based doublet chemotherapy. Double-blind, randomized, placebo-controlled part: To compare progression free survival (PFS) by local investigator assessment as per RECIST 1.1 and overall survival (OS) between the two treatment arms. ; Secondary Objective: Safety run-in part: 1. To characterize PK of canakinumab in combination with pembrolizumab plus platinum-based doublet chemotherapy 2. To characterize safety and tolerability of canakinumab in combination with pembrolizumab plus platinum-based doublet chemotherapy 3. To assess preliminary clinical anti-tumor activity (ORR, DCR and DOR) of canakinumab in combination with pembrolizumab plus platinum-based chemotherapy 4. To characterize immunogenicity (anti-drug antibodies) of canakinumab and pembrolizumab Double-blind, randomized, placebo-controlled part: 1. To evaluate ORR, DCR, time to response and DOR by local investigator assessment per RECIST 1.1 in the treatment arms 2. To characterize the safety profile of the treatment arms 3. To characterize PK of canakinumab, pembrolizumab and chemotherapy 4. To characterize immunogenicity (ADA) of canakinumab and pembrolizumab 5. To assess PROs including symptoms, physical functioning and health-related QOL in the treatment arms ; Primary end point(s): Safety run-in part: Incidence of dose limiting toxicities in the first 42 days of study treatment. Double-blind, randomized, placebo-controlled part: PFS based on local investigator assessment as per RECIST 1.1 and OS ; Timepoint(s) of evaluation of this end point: Safety run-in part: | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Safety run-in part: 1. Concentration and PK parameters of canakinumab, pembrolizumab and chemotherapy 2. Type, frequency and severity of adverse events and reactions, changes in laboratory values, vital signs, ECGs 3. ORR, DCR, DOR by investigator’s assessment according to RECIST 1.1 4. Anti-drug antibodies (ADA) prevalence at baseline and ADA incidence on-treatment of canakinumab and pembrolizumab Double-blind, randomized, placebo-controlled part: 1. ORR, DCR, TTR and DOR based on local investigator assessment as per RECIST 1.1 2. Frequency of adverse events, serious adverse events, AEs leading to treatment discontinuation, proportion of patients with laboratory abnormalities, ECG, and vital signs. 3. Concentration and PK parameters of canakinumab, pembrolizumab and chemotherapy 4. Anti-drug antibodies (ADA) prevalence at baseline and ADA incidence on-treatment of canakinumab and pembrolizumab 5. Time to definitive 10-point deterioration symptom scores for chest pain, cough and dyspnea per QLQ-LC13 questionnaire as three primary PRO variables of interest and time to definitive deterioration in global health status/QoL, shortness of breath and pain per QLQ-C30 as secondary PRO variables of interest. ; Timepoint(s) of evaluation of this end point: Safety run-in part: The analysis will be conducted when at least 6 evaluable subjects (among approximately 9 subjects enrolled) in each of the 3 treatment cohorts have been observed for dose limiting toxicity (DLT) for at least 42 days. Double-blind, randomized, placebo-controlled part: Analysis will occur when approximately 253 PFS events are observed. | — |
Countries
Argentina, Australia, Austria, Brazil, Canada, Chile, China, Colombia, Czech Republic, Denmark, Finland, France, Germany, Greece, Guatemala, Hong Kong, Hungary, Iceland, India, Italy, Japan, Korea, Republic of, Lebanon, Malaysia, Mexico, Netherlands, Norway, Peru, Philippines, Poland, Portugal, Romania, Russian Federation, Singapore, Slovakia, South Africa, Spain, Sweden, Switzerland, Taiwan, Thailand, Turkey, United Kingdom, United States, Vietnam
Contacts
Public ContactTrial Monitoring Organization (TMo)
Novartis Farmacéutica, S.A.
Outcome results
None listed