Non-small cell lung cancer MedDRA version: 21.1 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 Pharma AG
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: The main inclusion criteria are listed below. Other inclusion criteria, defined in the protocol, may apply. • Histologically confirmed locally advanced/metastatic (stage IIIBIV) NSCLC. • Subject has 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. • Serum lipase = 1.5 x ULN. • Creatinine clearance = 60 mL/ min by calculation using Cockcroft- Gault formula. 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 135 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 110
Exclusion criteria
Exclusion criteria: The main exclusion criteria are listed below. Other exclusion criteria, defined in the protocol, may apply. • Subject who previously received docetaxel, canakinumab (or another IL-1ß 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. • Subjects with pure squamous cell histology that are known to have EGFR/ ALK sensitizing mutations are excluded. • Subjects with known BRAF V600 mutation or ROS1 rearrangement will be excluded if required by local guidelines. • History of severe hypersensitivity reaction to monoclonal antibodies, taxanes or excipients of docetaxel or canakinumab. • Subject with suspected or proven immunocompromised state or infections, including evidence of active or latent tuberculosis (TB) as determined by locally approved screening methods. If the results of the screening per local treatment guidelines or clinical practice require treatment, then the patient is not eligible. • Subject with history of interstitial lung disease or pneumonitis grade = 2. • Participation in a prior investigational study within 30 days prior to enrollment or within 5-half lives of the investigational product (other than chemotherapy or checkpoint inhibitors), whichever is longer or those who are expected to receive any other investigational drug or device the conduct of the study.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: • Safety run-in part: To confirm the Recommended Phase 3 Regimen (RP3R) of the combination of canakinumab and docetaxel • Randomized part: To compare the overall survival (OS) in the docetaxel plus canakinumab arm versus docetaxel plus placebo arm ;Secondary Objective: Safety run-in part: • To assess preliminary clinical anti-tumor activity of canakinumab and docetaxel combination • To characterize safety and tolerability of the combination of canakinumab and docetaxel • To characterize pharmacokinetics of canakinumab and docetaxel when given in combination Randomized part: • To evaluate 2 treatment arms with regards to progression-free survival, overall response rate, disease control rate, Time to response and duration of response • To characterize safety profile of the combination of docetaxel and canakinumab • To assess effect of docetaxel plus canakinumab vs docetaxel plus placebo arms on PROs including lung cancer symptoms, healthrelated quality of life and health status • To characterize pharmacokinetics of canakinumab when given in combination • To characterize immunogenicity of canakinumab • To assess the effect of docetaxel plus placebo vs docetaxel plus canakinumab arms on ECOG performance status.;Primary end point(s): Safety Run-in Part : • Incidence rate of dose limiting toxicities (DLTs) in the first 42 days associated with the administration of canakinumab in combination with docetaxel. Randomized Part : • OS;Timepoint(s) of evaluation of this end point: Safety Run-in Part : No formal statistical evaluation timepoint. Randomized Part : The primary analysis will occur when approximately the required 137 targeted OS events is reached at the final analysis or earlier if the statistical significance is reached for OS at the time of interim analysis when approximately 96 OS events have been observed. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Safety Run-in Part : • Type, frequency and severity of adverse events, changes in laboratory values, vital signs, ECGs • ORR, DOR and DCR by investigator’s assessment according to RECIST 1.1 • Concentration of canakinumab/docetaxel and PK parameters Randomized Part : • PFS, ORR, DCR, TTR and DOR based on local investigator assessment per RECIST 1.1 • AEs (CTCAE v5.0), ECGs, vital signs and laboratory abnormalities • Time to definitive 10 point deterioration symptom scores of chest pain, cough and dyspnea per QLQLC13 questionnaire are primary PRO variables of interest. Time to definitive deterioration in global health status/QoL, shortness of breath and pain per QLQ-C30 are secondary PRO variables of interest. Change from baseline in EORTC-QLQ C30 and LC13, EQ-5D-5L • Concentration of canakinumab/docetaxel and PK parameters • Antidrug antibodies (ADA) prevalence at baseline and ADA incidence on-treatment • Time to definitive deterioration of the ECOG performance status of the score from baseline.;Timepoint(s) of evaluation of this end point: Safety Run-in Part : • The analysis of secondary endpoints after 2 treatment cycles Randomized Part : • The analysis of secondary endpoints will be performed with the primary OS analysis This primary analysis will occur when approximately the required 137 targeted OS events is reached at the final analysis or earlier if the statistical significance is reached for OS at the time of interim analysis when approximately 96 OS events have been observed. | — |
Countries
Argentina, Australia, Belgium, Brazil, Canada, Chile, China, Czechia, Czech Republic, Denmark, France, Germany, Greece, Hungary, Israel, Italy, Japan, Jordan, Korea, Republic of, Lebanon, Luxembourg, Netherlands, Poland, Russian Federation, Singapore, Spain, Taiwan, United States
Contacts
Public ContactPunkt informacyjny badania kliniczn
Novartis Pharma Services AG
Outcome results
None listed