A clinical trial to evaluate if CC-486 plus pembrolizumab works and is safe in patients with advanced or metastatic non-small cell lung cancer who have previously received platinum containing treatment.

• Register: EUCTR
• Last refreshed on: 16 November 2015
• Main ID: EUCTR2014-005614-29-FR
• Date of registration: 06/08/2015
• Prospective Registration: Yes
• Primary sponsor: Celgene Corporation
• Public title: A clinical trial to evaluate if CC-486 plus pembrolizumab works and is safe in patients with advanced or metastatic non-small cell lung cancer who have previously received platinum containing treatment.
• Scientific title: A Phase 2 multicenter, randomized, placebo controlled, double-blind study to assess the safety and efficacy of CC-486 (oral azacitidine) in combination with pembrolizumab (MK-3475) versus pembrolizumab plus placebo in subjects with previously treated locally advanced or metastatic non-small cell lung cancer
• Date of first enrolment: 29/09/2015
• Target sample size: 90
• Recruitment status: Authorised-recruitment may be ongoing or finished
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2014-005614-29
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: no Single blind: no Double blind: yes Parallel group: yes Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: yes Other: no Number of treatment arms in the trial: 2

Countries of recruitment

France, Germany, Greece, Italy, Spain, United States

Contacts

• Name: ClinicalTrialDisclosure
• Affiliation: Celgene Corporation

• Name: ClinicalTrialDisclosure
• Affiliation: Celgene Corporation

Key inclusion & exclusion 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 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:
-Subject has known sensitizing EGFR and/or positive ALK mutation
-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


Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Therapeutic area: Diseases [C] - Cancer [C04]

Second-line treatment of locally advanced or metastatic non-small cell lung cancer (NSCLC).
MedDRA version: 18.0 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: 18.0 Level: PT Classification code 10029521 Term: Non-small cell lung cancer stage IIIB System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
MedDRA version: 18.0 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 polyps)
MedDRA version: 18.0 Level: PT Classification code 10059515 Term: Non-small cell lung cancer metastatic System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
MedDRA version: 18.0 Level: PT Classification code 10061873 Term: Non-small cell lung cancer System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
MedDRA version: 18.0 Level: PT Classification code 10029515 Term: Non-small cell lung cancer recurrent System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Intervention(s)

Product Name: Oral Azacitidine
Product Code: CC-486
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: AZACITIDINE
CAS Number: 320-67-2
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 150-
Pharmaceutical form of the placebo: Film-coated tablet
Route of administration of the placebo: Oral use

Product Name: Oral Azacitidine
Product Code: CC-486
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: AZACITIDINE
CAS Number: 320-67-2
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 200-
Pharmaceutical form of the placebo: Film-coated tablet
Route of administration of the placebo: Oral use

Product Name: Pembrolizumab
Product Code: MK-3475
Pharmaceutical Form: Lyophilisate for solution for infusion
INN or Proposed INN: PEMBROLIZUMAB
Current Sponsor code: PEMBROLIZUMAB
Other descriptive name: PEMBROLIZUMAB
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 50-

Primary Outcome(s)

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

Timepoint(s) of evaluation of this end point: When 70 PFS events occur

Primary end point(s): •PFS measured as time from randomization to progression according to RECIST 1.1 (based on Investigator assessment)

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

Secondary Outcome(s)

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

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.

Secondary ID(s)

CC-486-NSCL-001

Source(s) of Monetary Support

Celgene Corporation