Neoplasms

Respiratory Tract (Lung and Bronchial) Diseases

All Conditions

Lung Neoplasms

Carcinoma, Non-Small-Cell Lung

Carcinoma

Respiratory Tract Neoplasms

Thoracic Neoplasms

Lung Diseases

Respiratory Tract Diseases

Carcinoma, Bronchogenic

Bronchial Neoplasms

Antineoplastic Agents

All Drugs and Chemicals

Paclitaxel

Azacitidine

Albumin-Bound Paclitaxel

Immunomodulating Agents

Durvalumab

Taxane

Cc-486

Tubulin Modulators

Antimitotic Agents

Antimetabolites

Enzyme Inhibitors

Subjects in the combination arm will receive nab-paclitaxel 100 mg\^/m2 intravenous (IV) infusion over 30 minutes on Days 8 and 15 and CC-486 200 mg orally daily (QD) on Days 1 to14 of each 21-day treatment cycle

Subjects in the monotherapy arm will receive nab-Paclitaxel 100 mg/m\^2 IV infusion over 30 minutes on Days 1 and 8 of each 21-day treatment cycle

subjects in the nab-Paclitaxel/durvalumab combination arm will receive nab-Paclitaxel 100 mg/m2 IV infusion over 30 minutes on Days 1 and 8 and durvalumab 1125 mg IV infusion over approximately 1 hour on Day 15 of each 21-day treatment cycle

nab-paclitaxel IV

CC-486

Duravalumab

Bristol-Myers Squibb

This is a Phase 2, open-label, multicenter study to assess the efficacy and safety of second/third-line treatment with nab-paclitaxel in combination with the epigenetic modifying therapy of CC-486 or immunotherapy of durvalumab, and nab-paclitaxel monotherapy in subjects with advanced non-small cell lung cancer (NSCLC).

This Phase 2 study will test the hypothesis that epigenetic modifying therapy of CC-486 or immunotherapy of durvalumab can improve the anti-tumor activity of nab-paclitaxel in subjects with advanced non-small cell lung cancer (NSCLC) who have received no more than one prior chemotherapy regimen for their advanced disease. It will further assess efficacy and safety of nab-paclitaxel monotherapy in this setting. Each subject will receive study therapy as second- or third-line of treatment. Approximately 240 male and female subjects with advanced NSCLC will be assigned to one of the following treatment arms (approximately 80 subjects per group): nab-paclitaxel /CC-486 combination therapy, nab-paclitaxel/durvalumab combination therapy or nab-paclitaxel monotherapy prior to receiving first dose of Investigational Product. A permuted-block randomization method will be employed to assign the subjects among the treatment arms that are enrolling simultaneously, when applicable, stratified by the following baseline factors: ECOG performance status (0 versus 1), gender (males versus females), and smoker (yes versus no). Treatment assignments of subjects to the nab-paclitaxel/CC-486 combination therapy and nab-paclitaxel monotherapy arms will be conducted completely in a randomized fashion.

Safety and Efficacy Study of Nab®-Paclitaxel With CC-486 or Nab®-Paclitaxel With Durvalumab, and Nab®-Paclitaxel Monotherapy as Second/Third-line Treatment for Advanced Non-small Cell Lung Cancer

A Phase 2, Open-Label, Multi-Center Study to Assess Safety and Efficacy of Second/Third-Line Treatment With NAB®-Paclitaxel (ABI-007) In Combination With Epigenetic Modifying Therapy Of CC-486, Or Immunotherapy of Durvalumab (MEDI4736), Or As Monotherapy In Subjects With Advanced Non-Small Cell Lung Cancer (NSCLC): Abound.2L+

Progression-free survival was defined as the time in months from the date of randomization/assignment to the date of disease progression according to Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 criteria documented by computed tomography (CT) scan, not including symptomatic deterioration, or death (any cause) on or prior to the clinical cut-off date, which ever occurred earlier. Participants who did not have disease progression and had not died, regardless of whether they were discontinued from treatment, were censored at the date of last tumor assessment, on or prior to the clinical cut-off date that the participant was progression free. Progressive Disease was defined as at least a 20% increase in the sum of diameters of target lesions from nadir.

Disease control rate was defined as the percentage of participants who had a CR, PR or SD during the course of the study, according to RECIST version 1.1 criteria, as evaluated by the investigator. RECIST Version 1.1 criteria is defined as follows:

* Complete Response is the disappearance of all target lesions;
* Partial Response is at least a 30% decrease in the sum of diameters of target lesions from baseline;
* Stable Disease is neither sufficient shrinkage to qualify for PR nor sufficient increase of lesions to qualify for progressive disease. Responses were evaluated every 6 weeks.

Overall Response was defined as percentage of participants who achieved a radiologic confirmed complete response or partial response according to RECIST V 1.1 criteria and compared with baseline among all tumor assessments, where baseline was the last CT obtained prior to or on Day 1 of treatment. Per RECIST V 1.1 criteria, a CR is defined as a disappearance of all target lesions; a PR is defined as having at least a 30% decrease in the sum of diameters of target lesions from baseline. Responses were evaluated every 6 weeks.

Overall survival was defined as the time in months between randomization/treatment assignment 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.

TEAEs were defined as any adverse event or serious adverse event that occurred or worsened on or after the day of the first dose of the IP through 28 days after the last dose of IP for Arms A and C or up to 90 days after the last dose for Arm B, and those SAEs made known to the investigator at any time thereafter that are suspected of being related to IP. A serious AE (SAE) = any AE which results in death; is life-threatening; requires inpatient hospitalization or prolongation of existing hospitalization; results in persistent or significant disability/incapacity; is a congenital anomaly/birth defect; constitutes an important medical event. The severity of AEs were graded based on National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE), Version 4.0 and the scale: Grade 1 = Mild l intervention/therapy required Grade 2 = Moderate Grade 3 = Severe Grade 4 = Life threatening Grade 5 = Death.

The discontinuation rate was defined as the percentage of participants who had study drug discontinued and was assessed throughout the conduct of the study.

Dose intensity was the cumulative dose divided by the dosing period in weeks.

Dose intensity was the cumulative dose divided by the dosing period in weeks).

A dose reduction occurred when the dose assigned at a visit was lower than the dose assigned at the previous visit. Dose reductions were typically caused by clinically significant laboratory abnormalities and/or TEAEs or toxicities.

Celgene

Participants received nab-paclitaxel 100 mg/m\^2 by intravenous (IV) infusion over 30 minutes on Days 8 and 15 and CC-486 200 mg tablets on Days 1 to 14 of each 21-day treatment cycle until disease progression (DP), development of an unacceptable toxicity, death, lost to follow-up, or withdrawal of consent, in accordance with local standard of care.

Nab-Paclitaxel + CC-486 Combination Arm

Participants received nab-paclitaxel 100 mg/m\^2 by IV infusion over 30 minutes on Days 1and 8 and durvalumab (durva) 1125 mg/m\^2 by IV infusion over 1 hour on Day 15 of each 21-day treatment cycle until disease progression, development of an unacceptable toxicity, death, lost to follow-up, or withdrawal of consent, in accordance with local standard of care.

Nab-Paclitaxel + Durvalumab Combination Arm

Participants received nab-paclitaxel 100 mg/m\^2 by intravenous infusion over 30 minutes on Days 1 and 8 each 21-day treatment cycle until disease progression, development of an unacceptable toxicity, death, lost to follow-up, or withdrawal of consent, in accordance with local standard of care.

Nab-Paclitaxel Monotherapy Arm

Total

Age, Continuous

Sex: Female, Male

Race/Ethnicity, Customized

ECOG performance status is used by doctors and researchers to assess how a subject's disease is progressing, assess how the disease affects the daily living activities of the subject and determine appropriate treatment and prognosis. 0 = Fully Active (Most Favorable Activity); 1 = Restricted activity but ambulatory; 2 = Ambulatory but unable to carry out work activities; 3 = Limited Self-Care; 4 = Completely Disabled, No self-care (Least Favorable Activity)

Eastern Cooperative Oncology Group (ECOG) Performance Status

Current Smoker

Past Smoker

Never Smoked

Smoking History

Adenocarcinoma

Large Cell Carcinoma

Adenosquamous Carcinoma

Carcinoid Tumor

Other

Squamous Cell

Missing

Confirmed Histology

Stage IIIa

Stage IIIb

Stage IV

Not Reported

Disease stage means how big the tumor is and how far it has spread. Disease stages range from 0 (no spread) to IV (spread throughout the body). Stage 1 - the cancer is small and hasn't spread to the lymph nodes; Stage II - the cancer has spread to some lymph nodes near the tumor; Stage IIIA the cancer has spread to lymph nodes on the same side of the tumor; Stage IIIB - the the cancer has spread to the lymph nodes above the collarbone or in the opposite side of the chest tumor; Stage IV - the cancer has spread to other organs such as the other lung, brain or liver.

Disease Stage at Enrollment

Intent to Treat (ITT) Population included all assigned participants regardless of whether the participant received any investigational product (IP) or had any efficacy assessments performed.

Anne McClain, Senior Manager, Clinical Trial Disclosure

Based on stratified Cox proportional hazards regression model.

Nab-Paclitaxel Alone

Intent to Treat Population included all randomized or assigned participants regardless of whether the participant received any study drug or had any efficacy assessments performed.

Kaplan Meier Estimate of Progression-Free Survival (PFS) as Assessed by the Investigator

Direction of Disease Control Rate Ratio is DCR of Nab-Paclitaxel + CC-486 Combination Arm over DCR of Nab-Paclitaxel Alone

ITT Population included all randomized or assigned participants regardless of whether the participant received any study drug or had any efficacy assessments performed.

Percentage of Participants Who Achieved a Complete Response (CR), Partial Response (PR) or Stable Disease (SD) According to RECIST V 1.1 Criteria

Direction of Overall Response Rate Ratio is ORR of Nab-Paclitaxel + CC-486 Combination Arm over ORR of nab-Paclitaxel Alone.

Percentage of Participants Who Achieved a Best Overall Response of Complete Response or Partial Response According to RECIST V 1.1 Criteria

Kaplan Meier Estimate of Overall Survival (OS)

TEAE

Serious TEAE

Grade (GR) 3/4 TEAE

Grade 3 or Higher

Treatment Related TEAE

Treatment Related Serious TEAE

Treatment Related GR 3 or Higher TEAE

TEAE With Action to Reduce/Interrupt IP

Treatment-Related to Reduce or Interrupt IP

TEAE with Action Taken to Withdraw IP

TEAE with Fatal Outcome

Treatment Related TEAE with Fatal Outcome

Safety Population included all participants who were randomized or assigned and received at least 1 dose of study drug.

Number of Participants With Treatment Emergent Adverse Events (TEAEs) During the Entire Treatment Period

Treated population included all participants who were randomized or assigned and received at least 1 dose of study drug.

Percentage of Participants Who Discontinued Study Treatment

The treated population consisted of all participants who were randomized or assigned and received at least 1 dose of IP.

Dose Intensity Per Week of Nab-Paclitaxel

The treated population consisted of all participants who randomized or assigned and received at least 1 dose of IP.

Dose Intensity Per Week of CC-486

The treated population consisted of all participants who randomized or assigned and received at least 1 dose of investigational Product.

Dose Intensity Per Week of Durvalumab

Nab-Paclitaxel

Durvalumab (Reductions Not Allowed per Protocol)

The treated population consisted of all participants who were randomized or assigned and received at least 1 dose of investigational product.

Spots Global Cancer Trial Database for second line treatment of lung cancer