Second-line treatment of locally advanced or metastatic non-small cell lung cancer (NSCLC). MedDRA version: 18.1 Level: PT Classification code 10029522 Term: Non-small cell lung cancer stage IV System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) MedDRA version: 18.1 Level: LLT Classification code 10066490 Term: Progression of non-small cell lung cancer System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyp
Conditions
Sponsors
Celgene Corporation
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: -Subject is = 18 years of age at the time of signing the informed consent form. -Subject has histologically or cytologically confirmed squamous or non-squamous NSCLC. -Subject has stage IIIB or IV NSCLC and was pretreated with only 1 prior systemic platinum based chemotherapy. -Subject has provided a formalin fixed tumor tissue sample from a biopsy of a tumor lesion either at the time of or after the diagnosis of metastatic disease has been made AND from a site not previously irradiated to assess for PD-L1 status. -Subject has radiographically-documented measurable disease, as per RECIST 1.1. -Subject has an ECOG performance status of 0 to 1. -Subject has adequate organ and bone marrow functions 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 30 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 60
Exclusion criteria
Exclusion criteria: -Subject with non-squamous histology has known or unknown sensitizing EGFR and/or positive ALK mutation Note: Subjects with squamous histology and unknown EGFR and ALK mutational status are eligible. -Subject has received more than one line of therapy for stage IIIB or IV disease. -Subject has received prior therapy with any other anti-PD-1, or PD-L1 or PD-L2 agent or an antibody targeting other immuno-regulatory receptors or mechanism -Subject has had radiotherapy = 4 weeks or limited field radiation for palliation = 2 weeks prior to starting IP, and/or from whom = 30% of the bone marrow was irradiated. -Subject has received a live-virus vaccination within 30 days of planned treatment start. Seasonal flu vaccines that do not contain live virus are permitted -Subject has active autoimmune disease that has required systemic treatment within the past 2 years -Subject with uncontrolled or symptomatic central nervous system (CNS) metastases and/or carcinomatous meningitis Subjects with controlled and asymptomatic CNS metastases may participate in this trial. The patient must have completed any prior treatment for CNS metastases (must include radiotherapy and/or surgery) >= 28 days (>= 14 days for stereotactic radiosurgery). Patients must not be receiving corticosteroids for brain metastases.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: • To estimate the efficacy of CC-486 plus pembrolizumab versus pembrolizumab plus placebo based on PFS as measured using RECIST 1.1 criteria;Secondary Objective: •To estimate DCR of CC-486 plus pembrolizumab versus pembrolizumab plus placebo •To estimate OS of CC-486 plus pembrolizumab versus pembrolizumab plus placebo •To estimate ORR of CC-486 plus pembrolizumab versus pembrolizumab plus placebo •To evaluate safety and tolerability of CC-486 plus pembrolizumab versus pembrolizumab plus placebo •To evaluate the impact of pembrolizumab on the pharmacokinetics of CC-486;Primary end point(s): •PFS measured as time from randomization to progression according to RECIST 1.1 (based on Investigator assessment) ;Timepoint(s) of evaluation of this end point: When 70 PFS events occur | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1.Number (%) of subjects with SD for = 18 weeks, complete response (CR) or PR (DCR). 2.Overall survival. 3.Number (%) of subjects who achieve an objective CR or PR (ORR). 4.Safety to include the incidence of treatment-emergent adverse events (TEAEs), serious TEAEs, Grade 3-4 TEAEs, TEAEs of special interest, and laboratory abnormalities and other safety parameters. 5.Plasma PK parameters such as maximum observed concentration (Cmax), area under the concentration-time curve (AUC), time to maximum concentration (Tmax), terminal half-life (t1/2), apparent total body clearance (CL/F) and apparent volume of distribution (Vz/F) for CC-486.;Timepoint(s) of evaluation of this end point: 1.Every 6 weeks from randomization for the first 24 weeks then every 9 weeks until disease progression or start of a new anticancer treatment, or withdrawal of consent 2.When 70 deaths occur 3.Every 6 weeks from randomization for the first 24 weeks then every 9 weeks until disease progression or start of a new anticancer treatment, or withdrawal of consent 4.Continuous after informed consent signature 5.Predose, 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, and 8 hours post-dose | — |
Countries
France, Germany, Greece, Italy, Spain, United States
Contacts
Public ContactClinicalTrialDisclosure
Celgene Corporation
Outcome results
None listed