NCT02546986

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

Completed Phase 2 Results posted Last updated 8 August 2025

What this trial tests

Phase 2 trial testing CC-486 in Carcinoma, Non-Small-Cell Lung in 100 participants. Completed in 7 July 2025.

Timeline

9 October 2015

Primary endpoint
13 April 2017

7 July 2025

Quick facts

Lead sponsor	Celgene
Phase	Phase 2
Status	Completed
Study type	INTERVENTIONAL
Allocation	randomized
Design	parallel
Masking	quadruple
Primary purpose	treatment
Enrollment	100
Start date	9 October 2015
Primary completion	13 April 2017
Estimated completion	7 July 2025
Sites	33 locations across France, Italy, Greece, Germany, United States, Spain

Drugs / interventions tested

• CC-486
• Pembrolizumab (pembrolizumab) — full drug profile →
• Placebo

Conditions studied

• Carcinoma, Non-Small-Cell Lung — all drugs for Carcinoma, Non-Small-Cell Lung →

Sponsor

Celgene — full company profile →

Who can join

18 and older, any sex, with Carcinoma, Non-Small-Cell Lung. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

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

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 pr

Group	Value	95% CI
CC-486 and Pembrolizumab (CC-486 + PBZ)	2.9	1.8 – 4.0
Placebo and Pembrolizumab (PBO + PBZ)	4.0	1.5 – 8.0

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 Secondary · 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

Disease control rate was defined as the percentage of participants who had confirmed stable disease, complete or partial response during the course of study, according to RECIST v1.1, as evaluated by the investigator. RECIST v 1.1 is defined as: * Complete response: disappearance of all target lesions * Partial response: at least a 30% decrease in the sum of diameters of target lesions from baseline * Stable disease: neither sufficient shrinkage to qualify for PR nor sufficient increase of lesions to qualify for progressive disease * Progressive Disease (PD): at least a 20% increase in the s

Group	Value	95% CI
CC-486 and Pembrolizumab (CC-486 + PBZ)	25.5	15.8 – 37.4
Placebo and Pembrolizumab (PBO + PBZ)	38.8	27.1 – 51.5

Kaplan Meier Estimate of Overall Survival Secondary · 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

Overall survival (OS) was defined as the time in months between day 1 of treatment and death from any cause. Participants who were still alive as of the clinical cut-off date had their OS censored at the date of last contact or clinical cut-off, whichever was earlier. Participants who were lost to follow-up prior to the end of the study or who were withdrawn from the study were censored at the time of last contact.

Group	Value	95% CI
CC-486 and Pembrolizumab (CC-486 + PBZ)	11.9	7.2 – NA
Placebo and Pembrolizumab (PBO + PBZ)	NA	11.0 – NA

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

The best overall response is defined as the percentage of participants who achieved an objective confirmed complete response or partial response according to RECIST v1.1, compared with baseline where baseline was the last computed tomography (CT) scan obtained prior to or on day 1 of study treatment. RECIST v1.1 is defined as: * Complete response: disappearance of all target lesions * Partial response: at least a 30% decrease in the sum of diameters of target lesions from baseline * Stable disease: neither sufficient shrinkage to qualify for PR nor sufficient increase of lesions to qualify f

Group	Value	95% CI
CC-486 and Pembrolizumab (CC-486 + PBZ)	19.6	11.0 – 31.0
Placebo and Pembrolizumab (PBO + PBZ)	14.3	6.9 – 25.2

Number of Participants With Treatment Emergent Adverse Events Secondary · 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

Treatment-emergent adverse events (TEAEs) were defined as any adverse event (AE) or serious adverse event (SAE) that occurred or worsened on or after the day of the first dose of the investigational product (IP) through 28 days after the last dose of IP. In addition, any SAE with an onset date more than 28 day after the last dose of IP that was assessed by the investigator as related to IP was considered a TEAE. The severity of AEs was graded based on National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE), Version 4.0 and based on the following scale: Grade 1 = Mild;

Any TEAE

Group	Value	95% CI
CC-486 and Pembrolizumab (CC-486 + PBZ)	51
Placebo and Pembrolizumab (PBO + PBZ)	49

Any TEAE Related to Study Drug

Group	Value	95% CI
CC-486 and Pembrolizumab (CC-486 + PBZ)	47
Placebo and Pembrolizumab (PBO + PBZ)	37

Any Serious TEAE

Group	Value	95% CI
CC-486 and Pembrolizumab (CC-486 + PBZ)	31
Placebo and Pembrolizumab (PBO + PBZ)	27

Any Serious TEAE Related to Study Drug

Group	Value	95% CI
CC-486 and Pembrolizumab (CC-486 + PBZ)	12
Placebo and Pembrolizumab (PBO + PBZ)	6

Any CTC Grade 3/4 TEAE

Group	Value	95% CI
CC-486 and Pembrolizumab (CC-486 + PBZ)	40
Placebo and Pembrolizumab (PBO + PBZ)	27

Any CTC Grade 3/4 TEAE Related to Study Drug

Group	Value	95% CI
CC-486 and Pembrolizumab (CC-486 + PBZ)	25
Placebo and Pembrolizumab (PBO + PBZ)	10

Any TEAE Leading to Death

Group	Value	95% CI
CC-486 and Pembrolizumab (CC-486 + PBZ)	6
Placebo and Pembrolizumab (PBO + PBZ)	9

Any TEAE Leading to Dose Reduction

Group	Value	95% CI
CC-486 and Pembrolizumab (CC-486 + PBZ)	10
Placebo and Pembrolizumab (PBO + PBZ)	1

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

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 initiat

Group	Value	95% CI
CC-486 and Pembrolizumab (CC-486 + PBZ)	2.9	1.8 – 4.0
Placebo and Pembrolizumab (PBO + PBZ)	4.0	1.5 – 7.0

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

Area under the plasma concentration-time curve from Time 0 extrapolated to infinity, calculated as \[AUCt + Ct/ λz\]. Ct is the last quantifiable concentration. No AUC extrapolation was performed with unreliable λz. If AUC % extrap is ≥25%, AUCi inf was not reported.

Cycle 1 Day 1

Group	Value	95% CI
CC-486 and Pembrolizumab (CC-486 + PBZ)	156.0	± 82.64

Cycle 2 Day 1

Group	Value	95% CI
CC-486 and Pembrolizumab (CC-486 + PBZ)	212.7	± 78.06

Area Under the Plasma Concentration-time Curve From Time Zero to the Last Measurable Concentration (AUCt) of CC-486 Secondary · 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

Area under the plasma concentration-time curve from Time 0 to the time of the last quantifiable concentration, calculated by linear trapezoidal method when concentrations are increasing and the logarithmic trapezoidal method when concentrations are decreasing.

Cycle 1 Day 1

Group	Value	95% CI
CC-486 and Pembrolizumab (CC-486 + PBZ)	152.3	± 85.67

Cycle 2 Day 1

Group	Value	95% CI
CC-486 and Pembrolizumab (CC-486 + PBZ)	196.6	± 88.63

Maximum Observed Plasma Concentration (Cmax) of CC-486 Secondary · 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

Maximum observed plasma concentration, obtained directly from the observed concentration versus time data.

Cycle 1 Day 1

Group	Value	95% CI
CC-486 and Pembrolizumab (CC-486 + PBZ)	94.7	± 69.49

Cycle 2 Day 1

Group	Value	95% CI
CC-486 and Pembrolizumab (CC-486 + PBZ)	110.0	± 73.46

Time to Maximum Plasma Concentration (Tmax) of CC-486 Secondary · 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

Time to maximum observed plasma concentration obtained directly from the observed concentration versus time data.

Cycle 1 Day 1

Group	Value	95% CI
CC-486 and Pembrolizumab (CC-486 + PBZ)	1.5	0.5 – 3.0

Cycle 2 Day 1

Group	Value	95% CI
CC-486 and Pembrolizumab (CC-486 + PBZ)	1.5	0.5 – 3.5

Terminal Phase of Half-life (T1/2) of CC-486 Secondary · 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

Terminal phase half-life in plasma, calculated as \[(ln 2)/λz\]. t1/2 was only be calculated when a reliable estimate for λz could be obtained.

Cycle 1 Day 1

Group	Value	95% CI
CC-486 and Pembrolizumab (CC-486 + PBZ)	0.7	± 30.22

Cycle 2 Day 1

Group	Value	95% CI
CC-486 and Pembrolizumab (CC-486 + PBZ)	0.9	± 91.72

Apparent Total Plasma Clearance (CL/F) of CC-486 Secondary · 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

Apparent total plasma clearance (CL/F) of CC-486 was calculated as Dose/AUC∞

Cycle 1 Day 1

Group	Value	95% CI
CC-486 and Pembrolizumab (CC-486 + PBZ)	1922.7	± 82.64

Cycle 2 Day 1

Group	Value	95% CI
CC-486 and Pembrolizumab (CC-486 + PBZ)	1410.4	± 78.06

Adverse events — posted to ClinicalTrials.gov

Time frame: 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 for the PBZ + PBO arm.. Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

CC-486+Pembrolizumab

Serious: 31/51 (61%)

Deaths: 23/51

Pembrolizumab+Placebo

Serious: 27/49 (55%)

Deaths: 20/49

Serious adverse events (63 terms)

Reaction	System	CC-486+Pembrolizumab	Pembrolizumab+Placebo
Nausea	Gastrointestinal disorders	—	—
Vomiting	Gastrointestinal disorders	—	—
Pneumonia	Infections and infestations	—	—
Dyspnoea	Respiratory, thoracic and mediastinal disorders	—	—
Diarrhoea	Gastrointestinal disorders	—	—
General physical health deterioration	General disorders	—	—
Pyrexia	General disorders	—	—
Haemoptysis	Respiratory, thoracic and mediastinal disorders	—	—
Respiratory failure	Respiratory, thoracic and mediastinal disorders	—	—
Febrile neutropenia	Blood and lymphatic system disorders	—	—
Colitis	Gastrointestinal disorders	—	—
Hepatic failure	Hepatobiliary disorders	—	—
Pericardial effusion	Cardiac disorders	—	—
Diplopia	Eye disorders	—	—
Abdominal pain	Gastrointestinal disorders	—	—
Intestinal perforation	Gastrointestinal disorders	—	—
Asthenia	General disorders	—	—
Death	General disorders	—	—
Fatigue	General disorders	—	—
Non-cardiac chest pain	General disorders	—	—
Autoimmune hepatitis	Hepatobiliary disorders	—	—
Cholelithiasis	Hepatobiliary disorders	—	—
Hepatitis toxic	Hepatobiliary disorders	—	—
Hypertransaminasaemia	Hepatobiliary disorders	—	—
Bronchitis	Infections and infestations	—	—

Other adverse events (60 terms — click to expand)

Reaction	System	CC-486+Pembrolizumab	Pembrolizumab+Placebo
Nausea	Gastrointestinal disorders	—	—
Vomiting	Gastrointestinal disorders	—	—
Asthenia	General disorders	—	—
Diarrhoea	Gastrointestinal disorders	—	—
Decreased appetite	Metabolism and nutrition disorders	—	—
Constipation	Gastrointestinal disorders	—	—
Pyrexia	General disorders	—	—
Cough	Respiratory, thoracic and mediastinal disorders	—	—
Anaemia	Blood and lymphatic system disorders	—	—
Weight decreased	Investigations	—	—
Dyspnoea	Respiratory, thoracic and mediastinal disorders	—	—
Fatigue	General disorders	—	—
Back pain	Musculoskeletal and connective tissue disorders	—	—
Neutropenia	Blood and lymphatic system disorders	—	—
Abdominal pain	Gastrointestinal disorders	—	—
Oedema peripheral	General disorders	—	—
Cancer pain	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	—	—
Hypokalaemia	Metabolism and nutrition disorders	—	—
Hypomagnesaemia	Metabolism and nutrition disorders	—	—
Hypertension	Vascular disorders	—	—
Abdominal pain upper	Gastrointestinal disorders	—	—
Bronchitis	Infections and infestations	—	—
Upper respiratory tract infection	Infections and infestations	—	—
Musculoskeletal pain	Musculoskeletal and connective tissue disorders	—	—
Myalgia	Musculoskeletal and connective tissue disorders	—	—
Pain in extremity	Musculoskeletal and connective tissue disorders	—	—
Dizziness	Nervous system disorders	—	—
Headache	Nervous system disorders	—	—
Dyspepsia	Gastrointestinal disorders	—	—
Stomatitis	Gastrointestinal disorders	—	—
Non-cardiac chest pain	General disorders	—	—
Alanine aminotransferase increased	Investigations	—	—
Aspartate aminotransferase increased	Investigations	—	—
Blood alkaline phosphatase increased	Investigations	—	—
Hyponatraemia	Metabolism and nutrition disorders	—	—
Arthralgia	Musculoskeletal and connective tissue disorders	—	—
Bone pain	Musculoskeletal and connective tissue disorders	—	—
Musculoskeletal chest pain	Musculoskeletal and connective tissue disorders	—	—
Paraesthesia	Nervous system disorders	—	—
Anxiety	Psychiatric disorders	—	—

Most-reported serious reactions: Nausea, Vomiting, Pneumonia, Dyspnoea, Diarrhoea, General physical health deterioration, Pyrexia, Haemoptysis.

Data from ClinicalTrials.gov NCT02546986 adverse events section.

Sponsor's own description

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.

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

1. Targeting epigenetic regulators for cancer therapy: mechanisms and advances in clinical trials.
   Cheng Y, He C, Wang M, Ma X, et al · · 2019 · cited 760× · PMID 31871779 · DOI 10.1038/s41392-019-0095-0
2. Immune checkpoint therapy in liver cancer.
   Xu F, Jin T, Zhu Y, Dai C. · · 2018 · cited 299× · PMID 29843754 · DOI 10.1186/s13046-018-0777-4
3. Lessons learned from the blockade of immune checkpoints in cancer immunotherapy.
   Li X, Shao C, Shi Y, Han W. · · 2018 · cited 284× · PMID 29482595 · DOI 10.1186/s13045-018-0578-4
4. Epigenetic regulation in the tumor microenvironment: molecular mechanisms and therapeutic targets.
   Yang J, Xu J, Wang W, Zhang B, et al · · 2023 · cited 251× · PMID 37217462 · DOI 10.1038/s41392-023-01480-x
5. Study and analysis of antitumor resistance mechanism of PD1/PD-L1 immune checkpoint blocker.
   Wang Z, Wu X. · · 2020 · cited 147× · PMID 32875727 · DOI 10.1002/cam4.3410
6. Combining epigenetic and immune therapy to overcome cancer resistance.
   Gomez S, Tabernacki T, Kobyra J, Roberts P, et al · · 2020 · cited 130× · PMID 31877341 · DOI 10.1016/j.semcancer.2019.12.019
7. Signaling pathways and targeted therapies in lung squamous cell carcinoma: mechanisms and clinical trials.
   Niu Z, Jin R, Zhang Y, Li H. · · 2022 · cited 127× · PMID 36198685 · DOI 10.1038/s41392-022-01200-x
8. Recent developments in epigenetic cancer therapeutics: clinical advancement and emerging trends.
   Nepali K, Liou JP. · · 2021 · cited 122× · PMID 33840388 · DOI 10.1186/s12929-021-00721-x