Safety and Efficacy Study of CC-486 With MK-3475 to Treat Locally Advanced or Metastatic Non-small Cell Lung Cancer

NCT02546986 | Completed Phase 2 Results DMC

• 1 other identifier: CC-486-NSCL-001
• Study Type: interventional
• Target: 100
• Locations: 6 countries
• Sites: 33

Brief Summary

The purpose of this study is to determine whether the combination therapy of CC-486 (oral azacitidine) and pembrolizumab provides improved patient outcomes compared to pembrolizumab alone in patients with previously treated locally advanced or metastatic non-small cell lung cancer.

Conditions

Carcinoma, Non-Small-Cell Lung

Keywords

CC-486; Azacitidine; Oral azacitidine; Methyltransferase inhibitor; Hypomethylation; Hypomethylating agent; Epigenetic; MK-3475; Pembrolizumab; Keytruda; PD-1; PD-L1; ImmunotherapyAdvanced non-small cell lung cancer; Metastatic non-small cell lung cancer; Non-small cell lung cancer; NSCLC; Merck Pembrolizumab (Keynote-117)

Outcome Measures

Primary Outcomes (2)

• Kaplan Meier Estimate of Progression-Free Survival (PFS) Based on Food and Drug Administration (FDA) Methodology

  PFS was defined according to the FDA Methodology as the time in months from the date of randomization to the date of disease progression according to Response Evaluation Criteria In Solid Tumors (RECIST) Version 1.1 (documented by computed tomography scan, not including symptomatic deterioration) or death for (any cause) on or prior to the clinical cutoff date, whichever occurred earlier. Those who did not have disease progression or had not died as of the data cutoff date were censored at the time of the last radiologic assessment where the participant was documented to be progression-free prior to the data cutoff date. Progressive disease includes at least a 20% increase in the sum of diameters of target lesions from nadir or appearance of a new lesion.

  From Day 1 of study drug treatment to the date of disease progression; up to the clinical cut-off date of 12 April 2017; overall maximum treatment duration was 61 weeks for the CC-486 + PBZ arm and 60 weeks for the PBZ + Placebo arm

• Kaplan Meier Estimate of Progression-Free Survival (PFS) Based on European Medicines Agency Methodology

  Progression-free survival was defined according to EMA methodology as the time from the date of randomization to the date of disease progression according to Response Evaluation Criteria In Solid Tumors (RECIST) Version 1.1 (documented by computed tomography scan result, not including symptomatic deterioration) or death for (any cause) on or prior to the data cutoff date, whichever occurred earlier. Participants who did not have disease progression or had not died were censored at the last known time that the participant was progression free. However, occasional missing observations or initiation of subsequent new anticancer therapy would not result in censoring for this analysis. Progressive disease is at least a 20% increase in the sum of diameters of target lesions from nadir or appearance of a new lesion.

  From Day 1 of study drug treatment to the date of disease progression; up to the clinical cut-off date of 12 April 2017; overall maximum treatment duration was 61 weeks for the CC-486 + PBZ arm and 60 weeks for the PBZ + Placebo arm

Secondary Outcomes (11)

• Percentage of Participants Who Achieved a Complete Response (CR), Partial Response (PR) or Stable Disease (SD) for a Minimum Duration of 18 Weeks Compared to Baseline

  Response was assessed every 6 weeks for the first 24 weeks, then every 9 weeks until DP, new anticancer initiation, or withdrawal of consent; maximum treatment exposure for CC-486 + PBZ was 61 weeks and 60 weeks for PBO +PBZ

• Kaplan Meier Estimate of Overall Survival

  From Day 1 of treatment up to the clinical cut-off date of 12 April 2017, whichever occurred earlier; median follow-up time for OS was 11.3 months in the CC-486 + PBZ arm and 12.2 months in the PBZ + Placebo arm

• Percentage of Participants Who Achieved a Best Overall Response of Complete Response or Partial Response

  Response was assessed every 6 weeks for the first 24 weeks, then every 9 weeks until DP, new anticancer initiation, or withdrawal of consent; maximum treatment exposure for CC-486 + PBZ was 61 weeks and 60 weeks for PBZ + PBO

• Number of Participants With Treatment Emergent Adverse Events

  From date of first dose of study treatment until 30 days after the last dose of IP; overall maximum treatment duration was 61 weeks for the CC-486 + PBZ arm and 60 weeks for the PBZ + Placebo arm

• Area Under the Plasma Concentration-time Curve From Time Zero to Infinity (AUC∞) of CC-486

  Pharmacokinetic (PK) blood samples collected at 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6 and 8 hours after CC-486 administration on Cycle 1 Day 1 and Cycle 2 Day 1

Study Arms (2)

CC-486 plus Pembrolizumab

EXPERIMENTAL

In the experimental arm, participants will receive a combination of two investigational drugs, CC-486 and pembrolizumab every 21-days.

Drug: CC-486; Drug: Pembrolizumab

Pembrolizumab plus Placebo

EXPERIMENTAL

In this control arm, participants will receive pembrolizumab as a 30 minute IV infusion on day 1 of each 21-day cycle and placebo will be administered by mouth daily on days 1 to 14 of each 21 day cycle. Placebo will also be administered in order to allow blinding of the study.

Drug: Pembrolizumab; Drug: Placebo

Interventions

CC-486 DRUG

CC-486 will be administered orally at a dose of 300 mg daily on days 1-14 of each 21-day cycle.

Also known as: Oral Azacitidine

CC-486 plus Pembrolizumab

Pembrolizumab DRUG

Pembrolizumab will be administered as a 30-minute IV infusion on day 1 of each 21-day cycle.

Also known as: MK-3475

CC-486 plus Pembrolizumab; Pembrolizumab plus Placebo

Placebo DRUG

Placebo will be administered orally daily on days 1-14 of each 21-day cycle.

Pembrolizumab plus Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Participant is ≥ 18 years of age at the time of signing the informed consent form.
• Participant has histologically or cytologically confirmed squamous or non-squamous non-small cell lung cancer (NSCLC).
• Participant has stage IIIB or IV NSCLC (American Joint Committee on Cancer \[AJCC\] Staging Manual, 7th edition \[Edge, 2009\]) and was pretreated with only 1 prior systemic platinum based chemotherapy.
• Participant 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 a protein known as Programmed death-ligand 1( PD-L1) status. Fine needle aspirates, endobronchial ultrasound (EBUS) or cell blocks are not acceptable. Needle or excisional biopsies, or resected tissue is required. Archival tissue may be acceptable. Submission of formalin-fixed paraffin embedded tumor tissue sample blocks are preferred; if submitting unstained slides, the slides should be freshly cut and submitted to the testing laboratory within 14 days from site slide sectioning date otherwise a new specimen will be requested.
• Participant has radiographically-documented measurable disease, as per Response Evaluation Criteria In Solid Tumors version 1.1 (RECIST v1.1).
• Particiapant has an Eastern Cancer Oncology Group (ECOG) performance status of 0 to 1.
• Participant has adequate organ functions, evidenced by the following:
• Aspartate aminotransferase (AST), Serum glutamic oxaloacetic transaminase (SGOT), alanine aminotransferase (ALT), serum glutamic pyruvic transaminase (SGPT) ≤ 2.5 x upper limit of normal range (ULN), or ≤ 5 x ULN range if liver metastasis present
• Total bilirubin ≤ 1.5 x ULN
• Serum creatinine ≤ 1.5 x ULN
• Potassium within normal range, or correctable with supplements
• Participant has adequate bone marrow function, evidenced by the following:
• Absolute neutrophil count ≥ 1.5 x 10\^9 cells/L
• Platelets ≥ 100 x 10\^9 cells/L
• Hemoglobin ≥ 9 g/dL

You may not qualify if:

• Participants with non-squamous histology has known or unknown sensitizing epidermal growth factor receptor (EGFR) and/or anaplastic lymphoma kinase positive (ALK) mutation. Note: Participants with squamous histology and unknown EGFR and ALK mutational status are eligible.
• Participant has received more than one line of therapy for stage IIIB or IV disease
• Participant has been previously treated with azacitidine (any formulation), decitabine, or any other hypomethylating agent.
• Particpant 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, including participation in any other pembrolizumab trial and treatment with pembrolizumab.
• a. Examples of such antibodies include (but are not limited to) antibodies against indoleamine 2,3-dioxygenase (IDO), PD-L1, IL-2R, glucocorticoid-induced tumor necrosis factor receptor (GITR).
• Participant has had a prior monoclonal antibody within 4 weeks prior to study Day 1 or who has not recovered (i.e. ≤ Grade 1 or at baseline) from adverse events due to agents administered more than 4 weeks earlier.
• Participant is currently participating and receiving study therapy or has participated in a study of an investigational agent and received study therapy or used an investigational device within 4 weeks prior to administration of pembrolizumab and CC-486
• Participant has previous severe hypersensitivity reaction to another monoclonal antibody (mAb).
• Participant has a known or suspected hypersensitivity to azacitidine, mannitol, or any other ingredient used in the manufacture of CC-486 (see the Azacitidine IB).
• Participant has had radiotherapy ≤ 4 weeks or limited field radiation for palliation
• Participant has received radiation therapy to the lung that is \> 30 Gy within 6 months of the first dose of trial treatment
• Participant has received a live-virus vaccination within 30 days of planned treatment start. Seasonal flu vaccines that do not contain live virus are permitted.
• Participant has not recovered from the acute toxic effects of prior anticancer therapy, radiation, or major surgery/significant trauma.
• Participant has an active infection requiring therapy.
• Participant has had an allogenetic tissue/solid organ ransplant.

Sponsors & Collaborators

• Celgene: lead

Study Sites (33)

Palo Verde Hematology Oncology

Glendale, Arizona, 85304, United States

Location

UCLA Hematology Oncology

Los Angeles, California, 90095, United States

Location

Georgetown University Medical Center

Washington D.C., District of Columbia, 20057, United States

Location

University Cancer and Blood Center, LLC

Athens, Georgia, 30607, United States

Location

Research Medical Center

Kansas City, Missouri, 64132, United States

Location

Washington Univ School of Medicine

St Louis, Missouri, 63110, United States

Location

North Shore Hematology Oncology Associates

East Setauket, New York, 11733-3456, United States

Location

Local Institution - 006

New York, New York, 10011, United States

Location

NYU Langone Medical Center

New York, New York, 10016, United States

Location

Vanderbilt Univ Medical Center

Nashville, Tennessee, 37232-6307, United States

Location

Local Institution - 204

Lyon, 69008, France

Location

Local Institution - 200

Marseille, 13915, France

Location

Local Institution - 203

Toulouse, 31059, France

Location

Local Institution - 201

Villejuif, 94805, France

Location

Local Institution - 302

Berlin, 13125, Germany

Location

Local Institution - 304

Cologne, 50937, Germany

Location

Local Institution - 300

Esslingen am Neckar, 73730, Germany

Location

Local Institution - 301

Löwenstein, 74245, Germany

Location

Local Institution - 903

Athens, 15562, Greece

Location

Local Institution - 601

Aviano, 33081, Italy

Location

Local Institution - 604

Catania, 95122, Italy

Location

Local Institution - 602

Milan, 20132, Italy

Location

Local Institution - 606

Milan, 20133, Italy

Location

Local Institution - 603

Napoli, Campania, 80131, Italy

Location

Local Institution - 600

Novara, 28100, Italy

Location

Local Institution - 605

Roma, 00128, Italy

Location

Local Institution - 705

Barakaldo, 48903, Spain

Location

Local Institution - 702

Barcelona, 08035, Spain

Location

Local Institution - 703

Madrid, 28034, Spain

Location

Local Institution - 701

Madrid, 28040, Spain

Location

Local Institution - 704

Madrid, 28040, Spain

Location

Local Institution - 706

Madrid, 28041, Spain

Location

Local Institution - 700

Valencia, 46014, Spain

Location

Related Links

• BMS Clinical Trial Information
• BMS Clinical Trial Patient Recruiting

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Interventions

cc-486; Azacitidine; pembrolizumab

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Aza Compounds; Organic Chemicals; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Ribonucleosides

Results Point of Contact

• Title: Anne McClain, Senior Manager, Clinical Trial Disclosure
• Organization: Celgene Corporation

ClinicalTrialDisclosure@Celgene.com

888-260-1599

Study Officials

• Bristol-Myers Squibb

  Bristol-Myers Squibb

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR
• Expanded Access: Yes

Study Record Dates

• First Submitted: August 20, 2015
• First Posted: September 11, 2015
• Study Start: October 9, 2015
• Primary Completion: April 13, 2017
• Study Completion: July 7, 2025
• Last Updated: August 8, 2025
• Results First Posted: May 14, 2018

Record last verified: 2025-07

Locations

US (10); FR (4); IT (7); DE (4); GR (1); ES (7)