abound2L+: 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

Sponsor
Celgene (Industry)
Overall Status
Active, not recruiting
CT.gov ID
NCT02250326
Collaborator
(none)
240
Enrollment
34
Locations
3
Arms
83.8
Anticipated Duration (Months)
7.1
Patients Per Site
0.1
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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).

Condition or DiseaseIntervention/TreatmentPhase
Phase 2

Detailed Description

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.

Study Design

Study Type:
Interventional
Actual Enrollment :
240 participants
Allocation:
Non-Randomized
Intervention Model:
Parallel Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
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+
Actual Study Start Date :
Jan 7, 2015
Actual Primary Completion Date :
Jul 17, 2017
Anticipated Study Completion Date :
Dec 31, 2021

Arms and Interventions

ArmIntervention/Treatment
Experimental: Combination arm: nab-paclitaxel and CC-486

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

Drug: nab-paclitaxel IV
nab-Paclitaxel intravenous (IV) infusion
Other Names:
  • Abraxane
  • ABI-007
  • Drug: CC-486
    Oral CC-486
    Other Names:
  • Oral AZA
  • Oral azacitidine
  • Experimental: Monotherapy arm: nab-paclitaxel IV infusion

    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

    Drug: nab-paclitaxel IV
    nab-Paclitaxel intravenous (IV) infusion
    Other Names:
  • Abraxane
  • ABI-007
  • Experimental: Nab-paclitaxel and Durvalumab combination

    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

    Drug: nab-paclitaxel IV
    nab-Paclitaxel intravenous (IV) infusion
    Other Names:
  • Abraxane
  • ABI-007
  • Drug: Duravalumab

    Outcome Measures

    Primary Outcome Measures

    1. Kaplan Meier Estimate of Progression-Free Survival (PFS) as Assessed by the Investigator [From date of first dose of IP to DP; up to data cut-off date of 30 August (Aug) 2017 for nab-paclitaxel and CC-486 + nab-paclitaxel and 23 December (Dec) 2017 for Durva + nab-paclitaxel; participants were followed for PFS for up to 18 months]

      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.

    Secondary Outcome Measures

    1. Percentage of Participants Who Achieved a Complete Response (CR), Partial Response (PR) or Stable Disease (SD) According to RECIST V 1.1 Criteria [Up to 30 Aug 2017 for nab-paclitaxel and CC-486 + nab-paclitaxel and 23 Dec 2017 for Durva + nab-paclitaxel; maximum treatment duration = 82.1 weeks, 52.6 weeks and 66.1 weeks for nab-paclitaxel, CC-486 + nab-paclitaxel and Durva + nab-paclitaxel]

      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.

    2. Percentage of Participants Who Achieved a Best Overall Response of Complete Response or Partial Response According to RECIST V 1.1 Criteria [Up to 30 Aug 2017 for nab-paclitaxel and CC-486 + nab-paclitaxel and 23 Dec 2017 for Durva + nab-paclitaxel; maximum treatment duration = 82.1 weeks, 52.6 weeks and 66.1 weeks for nab-paclitaxel, CC-486 + nab-paclitaxel and Durva + nab-paclitaxel]

      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.

    3. Kaplan Meier Estimate of Overall Survival (OS) [Up to 30 Aug 2017 for nab-paclitaxel and CC-486 + nab-paclitaxel and 23 Dec 2017 for Durva + nab-paclitaxel; participants were followed for overall survival up to 30 months]

      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.

    4. Number of Participants With Treatment Emergent Adverse Events (TEAEs) During the Entire Treatment Period [TEAEs were collected up to 4 weeks after receiving last dose of IP for nab-paclitaxel and CC-486 + nab-paclitaxel, and up to 90 days after the last IP dose for Durva + nab-paclitaxel; TEAEs were collected up to 86.1 weeks]

      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.

    5. Percentage of Participants Who Discontinued Study Treatment [Up to 30 Aug 2017 for nab-paclitaxel and CC-486 + nab-paclitaxel and 23 Dec 2017 for Durva + nab-paclitaxel; maximum treatment duration = 82.1 weeks, 52.6 weeks and 66.1 weeks for nab-paclitaxel, CC-486 + nab-paclitaxel and Durva + nab-paclitaxel]

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

    6. Dose Intensity Per Week of Nab-Paclitaxel [Up to 30 Aug 2017 for nab-paclitaxel and CC-486 + nab-paclitaxel and 23 Dec 2017 for Durva + nab-paclitaxel; maximum treatment duration = 82.1 weeks, 52.6 weeks and 66.1 weeks for nab-paclitaxel, CC-486 + nab-paclitaxel and Durva + nab-paclitaxel]

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

    7. Dose Intensity Per Week of CC-486 [Up to 30 Aug 2017 for nab-paclitaxel and CC-486 + nab-paclitaxel and 23 Dec 2017 for Durva + nab-paclitaxel; maximum treatment duration = 82.1 weeks, 52.6 weeks and 66.1 weeks for nab-paclitaxel, CC-486 + nab-paclitaxel and Durva + nab-paclitaxel]

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

    8. Dose Intensity Per Week of Durvalumab [Up to 30 Aug 2017 for nab-paclitaxel and CC-486 + nab-paclitaxel and 23 Dec 2017 for Durva + nab-paclitaxel; maximum treatment duration = 82.1 weeks, 52.6 weeks and 66.1 weeks for nab-paclitaxel, CC-486 + nab-paclitaxel and Durva + nab-paclitaxel]

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

    9. Percentage of Participants With Study Drug Dose Reductions [Up to 16 Jan 2017 for CC-486 + nab-paclitaxel and up to 23 Dec 2017 for nab-paclitaxel and Durva + nab-paclitaxel; maximum treatment duration = 82.1 weeks, 52.6 weeks and 66.1 weeks for nab-paclitaxel, CC-486 + nab-paclitaxel and Durva + nab-paclitaxel]

      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.

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No

    Inclusion Criteria: 1.Age ≥ 18 years the time of signing the Informed Consent Form (ICF).

    1. Understand and voluntarily provide written informed consent prior to the conduct of any study related assessments/procedures.

    2. Able to adhere to the study visit schedule and other protocol requirements. 4. Histologically or cytologically confirmed advanced NSCLC who will receive study therapy as second- or third-line of treatment for advanced disease.

    3. No other current active malignancy requiring anticancer therapy. 6. Radiographically documented measurable disease (defined by the presence of ≥ 1 radiographically documented measurable lesion).

    4. One prior platinum-containing chemotherapy for metastatic or recurrent NSCLC unless patients are ineligible to receive it. Patients may have received no more than one line of chemotherapy; immunotherapy in prior line of treatment (first or second line) is allowed. Absolute neutrophil count (ANC) ≥ 1500 cells/mm3.

    5. Platelets ≥ 100,000 cells/mm3. 9. Hemoglobin (Hgb) ≥ 9 g/dL. 10. Aspartate transaminase (AST/serum glutamic oxaloacetic transaminase [SGOT]) and alanine transaminase (ALT/serum glutamic pyruvic transaminase [SGPT]) ≤ 2.5 × upper limit of normal range (ULN) or ≤ 5.0 × ULN if liver metastases.

    6. Total bilirubin ≤ 1.5 ULN (unless there is a known history of Gilberts Syndrome).

    7. Serum creatinine ≤ 1.5 x ULN, or calculated creatinine clearance ≥ 60 mL/min (if renal impairment is suspected 24-hour urine collection for measurement is required).

    8. Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1. 14. Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1. 15. Females of childbearing potential [defined as a sexually mature woman who (1) have not undergone hysterectomy (the surgical removal of the uterus) or bilateral oophorectomy (the surgical removal of both ovaries) or (2) have not been naturally postmenopausal for at least 24 consecutive months (ie, has had menses at any time during the preceding 24 consecutive months)] must:

    9. Have a negative pregnancy test (ß-hCG) as verified by the study doctor within 72 hours prior to starting study therapy. She must agree to ongoing pregnancy testing during the course of the study, and after end of study therapy. This applies even if the subject practices true abstinence* from heterosexual contact.

    10. Either commit to true abstinence* from heterosexual contact (which must be reviewed on a monthly basis) or agree to use, and be able to comply with, effective contraception without interruption, 28 days prior to starting investigational product (IP), during the study therapy (including dose interruptions), and for 3 months after discontinuation of study therapy.

    Male subjects must:
    1. Practice true abstinence* or agree to use a condom during sexual contact with a pregnant female or a female of childbearing potential while participating in the study, during dose interruptions and for at least 6 months following IP discontinuation, even if he has undergone a successful vasectomy.

    2. Refrain from semen or sperm donation while taking durvalumab and for at least 3 months after the last dose of durvalumab.

    3. Females must abstain from breastfeeding during study participation and 3 months after IP discontinuation.

    Exclusion Criteria:
    • The presence of any of the following will exclude a subject from enrollment:
    1. Refractory to prior taxane therapy for advanced disease. Prior taxane used in the adjuvant setting does not exclude eligibility, provided there is no disease recurrence within 12 months upon completion of chemotherapy in that setting.

    2. Evidence of active brain metastases, including leptomeningeal involvement (prior evidence of brain metastasis are permitted only if asymptomatic and clinically stable for at least 8 weeks following completion of therapy). MRI of the brain (or CT scan w/contrast) is preferred.

    3. Only evidence of disease is non-measurable at study entry.

    4. Known activating EGFR mutations (such as exon 19 deletions or L858R).

    5. Known activating EML4-ALK mutations.

    6. Preexisting peripheral neuropathy of Grade > 2 (per NCI CTCAE v4.0).

    7. Any unresolved toxicity NCI CTCAE Grade ≥ 2 from previous anticancer therapy with the exception of alopecia, vitiligo, and the laboratory values defined in the inclusion criteria.

    8. Venous thromboembolism within 1 month prior to Cycle 1 Day 1.

    9. Current congestive heart failure (New York Heart Association Class II-IV).

    10. History of the following within 6 months prior to Cycle 1 Day 1: a myocardial infarction, severe/unstable angina pectoris, coronary/peripheral artery bypass graft, New York Heart Association (NYHA) Class III-IV heart failure, uncontrolled hypertension, clinically significant cardiac dysrhythmia or clinically significant electrocardiogram (ECG) abnormality, cerebrovascular accident, transient ischemic attack, or seizure disorder.

    11. Known hepatitis B or C virus (HBV/HCV) infection, known history of human immunodeficiency virus (HIV) infection, or receiving immunosuppressive or myelosuppressive medications that would in the opinion of the investigator, increase the risk of serious neutropenic complications, history of active primary immunodeficiency, active tuberculosis (clinical evaluation that includes clinical history, physical examination and radiographic findings, and TB testing in line with local practice).

    12. Active, uncontrolled bacterial, viral, or fungal infection(s) requiring systemic therapy, defined as ongoing signs/symptoms related to the infection without improvement despite appropriate antibiotics, antiviral therapy, and/or other treatment.

    13. History of interstitial lung disease, history of slowly progressive dyspnea and unproductive cough, sarcoidosis, silicosis, idiopathic pulmonary fibrosis, or pulmonary hypersensitivity pneumonitis or multiple allergies. Any lung disease that may interfere with the detection or management of suspected drug-related pulmonary toxicity.

    14. Subject has a clinically significant malabsorption syndrome, persistent diarrhea, or known sub-acute bowel obstruction > NCI CTCAE Grade 2, despite medical management.

    15. Treatment with any chemotherapy, investigational product, biologic or hormonal therapy for cancer treatment within 28 days prior to signing the ICF. Concurrent use of hormonal therapy for non-cancer-related conditions (e.g. hormone replacement therapy) is acceptable.

    16. History of or suspected allergy to any IP or their excipients.

    17. Major surgical procedure (as defined by the Investigator) within 28 days prior to the first dose of IP. Note: Local surgery of isolated lesions for palliative intent is acceptable.

    18. Currently enrolled in any other clinical protocol or investigational trial that involves administration of experimental therapy and/or therapeutic devices.

    19. Any other clinically significant medical condition, psychiatric illness, and/or organ dysfunction that will interfere with the administration of the therapy according to this protocol or which, in the views of investigator, preclude combination chemotherapy.

    20. Any other malignancy within 5 years prior to randomization/treatment assignement, or advanced malignant hepatic tumors, with the exception of adequately treated squamous cell carcinoma of the skin, in-situ carcinoma of the cervix, uteri, non-melanomatous skin cancer, carcinoma in situ of the breast, or incidental histological finding of prostate cancer (TNM Classification of Malignant Tumours (TNM) stage of T1a or T1b). (All treatment of which should have been completed 6 months prior to signing ICF).

    21. 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. Prior radiation therapy to a target lesion is permitted only if there has been clear progression of the lesion since radiation was completed.

    22. Any condition including the presence of laboratory abnormalities, which places the subject at unacceptable risk if he/she were to participate in the study.

    23. Any medical condition that confounds the ability to interpret data from the study.

    24. Female patients who are pregnant or breastfeeding or female patients of reproductive potential who are not willing to employ effective birth control from screening to 90 days after the last dose of durvalumab.

    25. Male patients of reproductive potential who are not willing to employ effective birth control from screenin to 90 days after the last dose of durvalumab and from screening to 6 months after the last dose of of nab-paclitaxel.

    26. History of allogenic organ transplantation.

    27. Current or prior use of immunosuppressive medication within 14 days before the first dose of durvalumab. The following are exceptions to this criterion:

    • Intranasal, inhaled, topical steroids, or local steroid injections (eg, intra articular injection)

    • Systemic corticosteroids at physiologic doses not to exceed 10 mg/day of prednisone or its equivalent

    • Steroids as premedication for hypersensitivity reactions (eg, CT scan premedication) 28. Receipt of live attenuated vaccine within 30 days prior to the first dose of IP. Note: Patients, if enrolled, should not receive live vaccine during the study and up to 30 days after the last dose of IP.

    1. Prior enrollment and treatment in a previous durvalumab clinical study. 30.
    Patients who have received prior anti-PD-1 or anti PD-L1:
    • Must not have experienced a toxicity that led to permanent discontinuation of prior immunotherapy.

    • All AEs while receiving prior immunotherapy must have completely resolved or resolved to baseline prior to screening for this study.

    • Must not have experienced a ≥ Grade 3 immune related AE or an immune related neurologic or ocular AE of any grade while receiving prior immunotherapy. NOTE: Subjects with endocrine AE of ≤ Grade 2 are permitted to enroll if they are stably maintained on appropriate replacement therapy and are asymptomatic.

    • Must not have required the use of additional immunosuppression other than corticosteroids for the management of an AE, not have experienced recurrence of an AE if re-challenged, and not currently require maintenance doses of > 10 mg prednisone or equivalent per day.

    Contacts and Locations

    Locations

    SiteCityStateCountryPostal Code
    1University of California San FranciscoSan FranciscoCaliforniaUnited States94143
    2Hospital of Central Connecticut Gynecologic OncologyNew BritainConnecticutUnited States06050
    3University Cancer and Blood Center, LLCAthensGeorgiaUnited States30607
    4Washington UniversitySaint LouisMissouriUnited States63110
    5John Theurer Cancer Center at Hackensack University Medical CenterHackensackNew JerseyUnited States07601
    6Weill Cornell Medical College - New York - Presbyterian HospitalNew YorkNew YorkUnited States10065
    7Penn State Milton S Hershey Medical CenterHersheyPennsylvaniaUnited States17033
    8Associates in Oncology and HematologyChattanoogaTennesseeUnited States37421
    9Millennium OncologyHoustonTexasUnited States77090
    10Ottawa Hospital Riverside CampusOttawaOntarioCanadaK1H 8L6
    11Royal Victoria Hospital McGill Department of Oncology(RVH)MontrealQuebecCanadaH3A 1A1
    12Hopital CalmetteLilleFrance59037
    13Centre Rene Gauducheau Centre de Lutte Contre Le Cancer Nantes AtlantiqueSaint HerblainFrance44805
    14Hopital Paul BrousseVillejuifFrance94800
    15Universitatsklinikum EssenEssenGermany45122
    16LungenClinic Grosshansdorf GmbHGrosshansdorfGermany22927
    17Klinik Loewenstein gGmbHLoewensteinGermany74245
    18Azienda Ospedaliero Universitaria Di Bologna - Policlinico S.Orsola MalpighiBolognaItaly40138
    19Azienda Ospedaliero Universitaria di ParmaParmaItaly43126
    20Azienda Ospedaliero-Universitaria Santa Maria della Misericordia die UdineUdineItaly33100
    21Hospital Universitario Germans Trias i PujolBarcelonaSpain08916
    22Hospital Universitari Vall d'HebronBarcelonaSpain8035
    23Hospital Universitario Ramon y CajalMadridSpain28034
    24Hospital 12 de OctubreMadridSpain28041
    25Hospital General Carlos HayaMalagaSpain29010
    26Hospital General Universitario de ValenciaValenciaSpain46014
    27Hospital Universitari i Politecnic La Fe de ValenciaValenciaSpain46026
    28Liverpool Heart and Chest HospitalBebington, WirralUnited KingdomCH63 4JY
    29Heart of England NHS Foundation TrustBirminghamUnited KingdomB9 5SS
    30Sarah Cannon Research Institute UKLondonUnited KingdomNW1 2BU
    31Charing Cross HospitalLondonUnited KingdomW6 8RF
    32University Hospital of South Manchester NHS Foundation Trust -Wythenshawe Hospital - North West LungManchesterUnited KingdomM23 9LT
    33Newcastle HospitalNewcastle Upon TyneUnited KingdomNE7 7DN
    34Churchhill HospitalOxfordUnited KingdomOX3 7LI

    Sponsors and Collaborators

    • Celgene

    Investigators

    • Study Director: Teng Jin Teng Jin Ong, MD, Celgene

    Study Documents (Full-Text)

    More Information

    Publications

    Responsible Party:
    Celgene
    ClinicalTrials.gov Identifier:
    NCT02250326
    Other Study ID Numbers:
    • ABI-007-NSCL-006
    • 2014-001105-41
    First Posted:
    Sep 26, 2014
    Last Update Posted:
    May 5, 2021
    Last Verified:
    Apr 1, 2021

    Study Results

    Participant Flow

    Recruitment DetailsThis was a multicenter study with 34 sites from the United States, Canada, France, Germany, Italy, Spain and the United Kingdom.
    Pre-assignment DetailEligible participants included those with advanced non-small cell lung cancer who had received no more than one prior containing chemotherapy regimen. Immunotherapy as a prior line of treatment was allowed. Randomization was stratified by eastern cooperative oncology group performance status, gender and the smoking status of the participant.
    Arm/Group TitleNab-Paclitaxel + CC-486 Combination ArmNab-Paclitaxel + Durvalumab Combination ArmNab-Paclitaxel Monotherapy Arm
    Arm/Group DescriptionParticipants 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.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.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.
    Period Title: Treatment Period
    STARTED817980
    Treated Population797879
    COMPLETED0153
    NOT COMPLETED816477
    Period Title: Treatment Period
    STARTED674364
    COMPLETED181326
    NOT COMPLETED493038

    Baseline Characteristics

    Arm/Group TitleNab-Paclitaxel + CC-486 Combination ArmNab-Paclitaxel + Durvalumab Combination ArmNab-Paclitaxel Monotherapy ArmTotal
    Arm/Group DescriptionParticipants 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.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.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.Total of all reporting groups
    Overall Participants817980240
    Age (years) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [years]
    64.0
    (9.00)
    62.7
    (10.74)
    62.6
    (9.58)
    63.1
    (9.77)
    Sex: Female, Male (Count of Participants)
    Female
    31
    38.3%
    25
    31.6%
    30
    37.5%
    86
    35.8%
    Male
    50
    61.7%
    54
    68.4%
    50
    62.5%
    154
    64.2%
    Race/Ethnicity, Customized (Count of Participants)
    Asian
    0
    0%
    0
    0%
    2
    2.5%
    2
    0.8%
    Black or African American
    0
    0%
    1
    1.3%
    2
    2.5%
    3
    1.3%
    White
    67
    82.7%
    77
    97.5%
    63
    78.8%
    207
    86.3%
    Other
    2
    2.5%
    0
    0%
    1
    1.3%
    3
    1.3%
    Not Reported
    12
    14.8%
    1
    1.3%
    12
    15%
    25
    10.4%
    Eastern Cooperative Oncology Group (ECOG) Performance Status (Count of Participants)
    0 = Fully Active
    25
    30.9%
    18
    22.8%
    26
    32.5%
    69
    28.8%
    1 = Restrictive but ambulatory
    56
    69.1%
    61
    77.2%
    54
    67.5%
    171
    71.3%
    2 = Ambulatory but unable to work
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Missing
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Smoking History (Count of Participants)
    Current Smoker
    18
    22.2%
    13
    16.5%
    13
    16.3%
    44
    18.3%
    Past Smoker
    54
    66.7%
    57
    72.2%
    63
    78.8%
    174
    72.5%
    Never Smoked
    9
    11.1%
    9
    11.4%
    4
    5%
    22
    9.2%
    Confirmed Histology (Count of Participants)
    Adenocarcinoma
    78
    96.3%
    48
    60.8%
    75
    93.8%
    201
    83.8%
    Large Cell Carcinoma
    1
    1.2%
    3
    3.8%
    4
    5%
    8
    3.3%
    Adenosquamous Carcinoma
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Carcinoid Tumor
    0
    0%
    1
    1.3%
    0
    0%
    1
    0.4%
    Other
    2
    2.5%
    3
    3.8%
    1
    1.3%
    6
    2.5%
    Squamous Cell
    0
    0%
    23
    29.1%
    0
    0%
    23
    9.6%
    Missing
    0
    0%
    1
    1.3%
    0
    0%
    1
    0.4%
    Disease Stage at Enrollment (Count of Participants)
    Stage IIIa
    1
    1.2%
    0
    0%
    1
    1.3%
    2
    0.8%
    Stage IIIb
    0
    0%
    3
    3.8%
    3
    3.8%
    6
    2.5%
    Stage IV
    80
    98.8%
    75
    94.9%
    76
    95%
    231
    96.3%
    Not Reported
    0
    0%
    1
    1.3%
    0
    0%
    1
    0.4%

    Outcome Measures

    1. Primary Outcome
    TitleKaplan Meier Estimate of Progression-Free Survival (PFS) as Assessed by the Investigator
    DescriptionProgression-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.
    Time FrameFrom date of first dose of IP to DP; up to data cut-off date of 30 August (Aug) 2017 for nab-paclitaxel and CC-486 + nab-paclitaxel and 23 December (Dec) 2017 for Durva + nab-paclitaxel; participants were followed for PFS for up to 18 months

    Outcome Measure Data

    Analysis Population Description
    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.
    Arm/Group TitleNab-Paclitaxel + CC-486 Combination ArmNab-Paclitaxel + Durvalumab Combination ArmNab-Paclitaxel Alone
    Arm/Group DescriptionParticipants 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.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.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.
    Measure Participants817980
    Median (95% Confidence Interval) [months]
    3.2
    4.5
    4.2
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Nab-Paclitaxel + CC-486 Combination Arm, Nab-Paclitaxel Alone
    Comments Based on stratified Cox proportional hazards regression model.
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesisp-Value
    Comments
    Method
    Comments
    Method of EstimationEstimation ParameterHazard Ratio (HR)
    Estimated Value1.3
    Confidence Interval (2-Sided) 95%
    0.90 to 1.94
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    2. Secondary Outcome
    TitlePercentage of Participants Who Achieved a Complete Response (CR), Partial Response (PR) or Stable Disease (SD) According to RECIST V 1.1 Criteria
    DescriptionDisease 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.
    Time FrameUp to 30 Aug 2017 for nab-paclitaxel and CC-486 + nab-paclitaxel and 23 Dec 2017 for Durva + nab-paclitaxel; maximum treatment duration = 82.1 weeks, 52.6 weeks and 66.1 weeks for nab-paclitaxel, CC-486 + nab-paclitaxel and Durva + nab-paclitaxel

    Outcome Measure Data

    Analysis Population Description
    ITT Population included all randomized or assigned participants regardless of whether the participant received any study drug or had any efficacy assessments performed.
    Arm/Group TitleNab-Paclitaxel + CC-486 Combination ArmNab-Paclitaxel + Durvalumab Combination ArmNab-Paclitaxel Alone
    Arm/Group DescriptionParticipants 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.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.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.
    Measure Participants817980
    Number (95% Confidence Interval) [Percentage of Participants]
    65.4
    80.7%
    70.9
    89.7%
    67.5
    84.4%
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Nab-Paclitaxel + CC-486 Combination Arm, Nab-Paclitaxel Alone
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesisp-Value
    Comments
    Method
    Comments
    Method of EstimationEstimation ParameterDisease Control Rate Ratio
    Estimated Value0.97
    Confidence Interval (2-Sided) 95%
    0.778 to 1.207
    Parameter Dispersion Type:
    Value:
    Estimation Comments95% CI was calculated using Clopper-Pearson method.
    Other Statistical AnalysisDirection of Disease Control Rate Ratio is DCR of Nab-Paclitaxel + CC-486 Combination Arm over DCR of Nab-Paclitaxel Alone
    3. Secondary Outcome
    TitlePercentage of Participants Who Achieved a Best Overall Response of Complete Response or Partial Response According to RECIST V 1.1 Criteria
    DescriptionOverall 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.
    Time FrameUp to 30 Aug 2017 for nab-paclitaxel and CC-486 + nab-paclitaxel and 23 Dec 2017 for Durva + nab-paclitaxel; maximum treatment duration = 82.1 weeks, 52.6 weeks and 66.1 weeks for nab-paclitaxel, CC-486 + nab-paclitaxel and Durva + nab-paclitaxel

    Outcome Measure Data

    Analysis Population Description
    ITT Population included all randomized or assigned participants regardless of whether the participant received any study drug or had any efficacy assessments performed.
    Arm/Group TitleNab-Paclitaxel + CC-486 Combination ArmNab-Paclitaxel + Durvalumab Combination ArmNab-Paclitaxel Alone
    Arm/Group DescriptionParticipants 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.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.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.
    Measure Participants817980
    Number (95% Confidence Interval) [percentage of participants]
    13.6
    16.8%
    27.8
    35.2%
    16.3
    20.4%
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Nab-Paclitaxel + CC-486 Combination Arm, Nab-Paclitaxel Alone
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesisp-Value
    Comments
    Method
    Comments
    Method of EstimationEstimation ParameterOverall Response Rate Ratio
    Estimated Value0.84
    Confidence Interval (2-Sided) 95%
    0.398 to 1.754
    Parameter Dispersion Type:
    Value:
    Estimation Comments95% CI was calculated using Clopper-Pearson method.
    Other Statistical AnalysisDirection of Overall Response Rate Ratio is ORR of Nab-Paclitaxel + CC-486 Combination Arm over ORR of nab-Paclitaxel Alone.
    4. Secondary Outcome
    TitleKaplan Meier Estimate of Overall Survival (OS)
    DescriptionOverall 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.
    Time FrameUp to 30 Aug 2017 for nab-paclitaxel and CC-486 + nab-paclitaxel and 23 Dec 2017 for Durva + nab-paclitaxel; participants were followed for overall survival up to 30 months

    Outcome Measure Data

    Analysis Population Description
    ITT Population included all randomized or assigned participants regardless of whether the participant received any study drug or had any efficacy assessments performed.
    Arm/Group TitleNab-Paclitaxel + CC-486 Combination ArmNab-Paclitaxel + Durvalumab Combination ArmNab-Paclitaxel Alone
    Arm/Group DescriptionParticipants 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.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.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.
    Measure Participants817980
    Median (95% Confidence Interval) [Months]
    8.1
    10.1
    17.0
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Nab-Paclitaxel + CC-486 Combination Arm, Nab-Paclitaxel Alone
    Comments Based on stratified Cox proportional hazards regression model.
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesisp-Value
    Comments
    Method
    Comments
    Method of EstimationEstimation ParameterHazard Ratio (HR)
    Estimated Value1.7
    Confidence Interval (2-Sided) 95%
    1.08 to 2.57
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    5. Secondary Outcome
    TitleNumber of Participants With Treatment Emergent Adverse Events (TEAEs) During the Entire Treatment Period
    DescriptionTEAEs 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.
    Time FrameTEAEs were collected up to 4 weeks after receiving last dose of IP for nab-paclitaxel and CC-486 + nab-paclitaxel, and up to 90 days after the last IP dose for Durva + nab-paclitaxel; TEAEs were collected up to 86.1 weeks

    Outcome Measure Data

    Analysis Population Description
    Safety Population included all participants who were randomized or assigned and received at least 1 dose of study drug.
    Arm/Group TitleNab-Paclitaxel + CC-486 Combination ArmNab-Paclitaxel + Durvalumab Combination ArmNab-Paclitaxel Alone
    Arm/Group DescriptionParticipants 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.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.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.
    Measure Participants797879
    TEAE
    79
    97.5%
    78
    98.7%
    78
    97.5%
    Serious TEAE
    30
    37%
    37
    46.8%
    29
    36.3%
    Grade (GR) 3/4 TEAE
    48
    59.3%
    53
    67.1%
    47
    58.8%
    Grade 3 or Higher
    49
    60.5%
    55
    69.6%
    47
    58.8%
    Treatment Related TEAE
    74
    91.4%
    71
    89.9%
    68
    85%
    Treatment Related Serious TEAE
    11
    13.6%
    17
    21.5%
    5
    6.3%
    Treatment Related GR 3 or Higher TEAE
    32
    39.5%
    32
    40.5%
    25
    31.3%
    TEAE With Action to Reduce/Interrupt IP
    49
    60.5%
    57
    72.2%
    38
    47.5%
    Treatment-Related to Reduce or Interrupt IP
    36
    44.4%
    32
    40.5%
    27
    33.8%
    TEAE with Action Taken to Withdraw IP
    8
    9.9%
    9
    11.4%
    8
    10%
    TEAE with Fatal Outcome
    4
    4.9%
    12
    15.2%
    3
    3.8%
    Treatment Related TEAE with Fatal Outcome
    0
    0%
    4
    5.1%
    1
    1.3%
    6. Secondary Outcome
    TitlePercentage of Participants Who Discontinued Study Treatment
    DescriptionThe discontinuation rate was defined as the percentage of participants who had study drug discontinued and was assessed throughout the conduct of the study.
    Time FrameUp to 30 Aug 2017 for nab-paclitaxel and CC-486 + nab-paclitaxel and 23 Dec 2017 for Durva + nab-paclitaxel; maximum treatment duration = 82.1 weeks, 52.6 weeks and 66.1 weeks for nab-paclitaxel, CC-486 + nab-paclitaxel and Durva + nab-paclitaxel

    Outcome Measure Data

    Analysis Population Description
    Treated population included all participants who were randomized or assigned and received at least 1 dose of study drug.
    Arm/Group TitleNab-Paclitaxel + CC-486 Combination ArmNab-Paclitaxel + Durvalumab Combination ArmNab-Paclitaxel Alone
    Arm/Group DescriptionParticipants 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.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.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.
    Measure Participants797980
    Number [percentage of participants]
    100.0
    123.5%
    80.8
    102.3%
    96.2
    120.3%
    7. Secondary Outcome
    TitleDose Intensity Per Week of Nab-Paclitaxel
    DescriptionDose intensity was the cumulative dose divided by the dosing period in weeks.
    Time FrameUp to 30 Aug 2017 for nab-paclitaxel and CC-486 + nab-paclitaxel and 23 Dec 2017 for Durva + nab-paclitaxel; maximum treatment duration = 82.1 weeks, 52.6 weeks and 66.1 weeks for nab-paclitaxel, CC-486 + nab-paclitaxel and Durva + nab-paclitaxel

    Outcome Measure Data

    Analysis Population Description
    The treated population consisted of all participants who were randomized or assigned and received at least 1 dose of IP.
    Arm/Group TitleNab-Paclitaxel + CC-486 Combination ArmNab-Paclitaxel + Durvalumab Combination ArmNab-Paclitaxel Alone
    Arm/Group DescriptionParticipants 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.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.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.
    Measure Participants797879
    Mean (Standard Deviation) [mg/m^2/week]
    54.73
    (11.390)
    57.18
    (13.605)
    58.61
    (14.893)
    8. Secondary Outcome
    TitleDose Intensity Per Week of CC-486
    DescriptionDose intensity was the cumulative dose divided by the dosing period in weeks.
    Time FrameUp to 30 Aug 2017 for nab-paclitaxel and CC-486 + nab-paclitaxel and 23 Dec 2017 for Durva + nab-paclitaxel; maximum treatment duration = 82.1 weeks, 52.6 weeks and 66.1 weeks for nab-paclitaxel, CC-486 + nab-paclitaxel and Durva + nab-paclitaxel

    Outcome Measure Data

    Analysis Population Description
    The treated population consisted of all participants who randomized or assigned and received at least 1 dose of IP.
    Arm/Group TitleNab-Paclitaxel + CC-486 Combination Arm
    Arm/Group DescriptionParticipants 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.
    Measure Participants79
    Mean (Standard Deviation) [mg/ week]
    716.66
    (220.945)
    9. Secondary Outcome
    TitleDose Intensity Per Week of Durvalumab
    DescriptionDose intensity was the cumulative dose divided by the dosing period in weeks).
    Time FrameUp to 30 Aug 2017 for nab-paclitaxel and CC-486 + nab-paclitaxel and 23 Dec 2017 for Durva + nab-paclitaxel; maximum treatment duration = 82.1 weeks, 52.6 weeks and 66.1 weeks for nab-paclitaxel, CC-486 + nab-paclitaxel and Durva + nab-paclitaxel

    Outcome Measure Data

    Analysis Population Description
    The treated population consisted of all participants who randomized or assigned and received at least 1 dose of investigational Product.
    Arm/Group TitleNab-Paclitaxel + Durvalumab Combination Arm
    Arm/Group DescriptionParticipants 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.
    Measure Participants77
    Mean (Standard Deviation) [mg/week]
    279.96
    (97.304)
    10. Secondary Outcome
    TitlePercentage of Participants With Study Drug Dose Reductions
    DescriptionA 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.
    Time FrameUp to 16 Jan 2017 for CC-486 + nab-paclitaxel and up to 23 Dec 2017 for nab-paclitaxel and Durva + nab-paclitaxel; maximum treatment duration = 82.1 weeks, 52.6 weeks and 66.1 weeks for nab-paclitaxel, CC-486 + nab-paclitaxel and Durva + nab-paclitaxel

    Outcome Measure Data

    Analysis Population Description
    The treated population consisted of all participants who were randomized or assigned and received at least 1 dose of investigational product.
    Arm/Group TitleNab-Paclitaxel + CC-486 Combination ArmNab-Paclitaxel + Durvalumab Combination ArmNab-Paclitaxel Alone
    Arm/Group DescriptionParticipants 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.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.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.
    Measure Participants797879
    Nab-Paclitaxel
    10.1
    12.5%
    14.1
    17.8%
    10.1
    12.6%
    CC-486
    20.3
    25.1%
    Durvalumab (Reductions Not Allowed per Protocol)
    0.0
    0%

    Adverse Events

    Time FrameTEAEs were collected up to 4 weeks after receiving last dose of IP for nab-paclitaxel and CC-486 + nab-paclitaxel, and up to 90 days after the last IP dose for Durva + nab-paclitaxel; TEAEs were collected up to 86.1 weeks
    Adverse Event Reporting Description
    Arm/Group TitleNab-Paclitaxel + CC-486 Combination ArmNab-Paclitaxel + Durvalumab Combination ArmNab-Paclitaxel Monotherapy Arm
    Arm/Group DescriptionParticipants 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.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.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.
    All Cause Mortality
    Nab-Paclitaxel + CC-486 Combination ArmNab-Paclitaxel + Durvalumab Combination ArmNab-Paclitaxel Monotherapy Arm
    Affected / at Risk (%)# EventsAffected / at Risk (%)# EventsAffected / at Risk (%)# Events
    Total53/81 (65.4%) 44/79 (55.7%) 37/80 (46.3%)
    Serious Adverse Events
    Nab-Paclitaxel + CC-486 Combination ArmNab-Paclitaxel + Durvalumab Combination ArmNab-Paclitaxel Monotherapy Arm
    Affected / at Risk (%)# EventsAffected / at Risk (%)# EventsAffected / at Risk (%)# Events
    Total30/79 (38%) 37/78 (47.4%) 29/79 (36.7%)
    Blood and lymphatic system disorders
    Anaemia0/79 (0%) 1/78 (1.3%) 0/79 (0%)
    Febrile neutropenia1/79 (1.3%) 0/78 (0%) 0/79 (0%)
    Cardiac disorders
    Atrial fibrillation0/79 (0%) 1/78 (1.3%) 0/79 (0%)
    Cardiac failure0/79 (0%) 0/78 (0%) 1/79 (1.3%)
    Endocrine disorders
    Adrenal insufficiency0/79 (0%) 3/78 (3.8%) 0/79 (0%)
    Gastrointestinal disorders
    Abdominal pain2/79 (2.5%) 0/78 (0%) 0/79 (0%)
    Diarrhoea1/79 (1.3%) 1/78 (1.3%) 0/79 (0%)
    Duodenal obstruction0/79 (0%) 0/78 (0%) 1/79 (1.3%)
    Flatulence1/79 (1.3%) 0/78 (0%) 0/79 (0%)
    Intestinal obstruction1/79 (1.3%) 0/78 (0%) 0/79 (0%)
    Nausea1/79 (1.3%) 1/78 (1.3%) 1/79 (1.3%)
    Vomiting2/79 (2.5%) 1/78 (1.3%) 1/79 (1.3%)
    General disorders
    Death0/79 (0%) 1/78 (1.3%) 0/79 (0%)
    General physical health deterioration2/79 (2.5%) 2/78 (2.6%) 1/79 (1.3%)
    Performance status decreased2/79 (2.5%) 1/78 (1.3%) 0/79 (0%)
    Pyrexia3/79 (3.8%) 2/78 (2.6%) 1/79 (1.3%)
    Sudden death1/79 (1.3%) 0/78 (0%) 0/79 (0%)
    Infections and infestations
    Abdominal wall abscess1/79 (1.3%) 0/78 (0%) 0/79 (0%)
    Bronchitis1/79 (1.3%) 0/78 (0%) 0/79 (0%)
    Cellulitis0/79 (0%) 1/78 (1.3%) 0/79 (0%)
    Infection0/79 (0%) 0/78 (0%) 1/79 (1.3%)
    Influenza1/79 (1.3%) 0/78 (0%) 0/79 (0%)
    Lower respiratory tract infection1/79 (1.3%) 2/78 (2.6%) 1/79 (1.3%)
    Lung infection0/79 (0%) 1/78 (1.3%) 0/79 (0%)
    Pneumocystis jirovecii pneumonia0/79 (0%) 1/78 (1.3%) 0/79 (0%)
    Pneumonia5/79 (6.3%) 8/78 (10.3%) 3/79 (3.8%)
    Pneumonia pneumococcal1/79 (1.3%) 0/78 (0%) 0/79 (0%)
    Postoperative wound infection0/79 (0%) 0/78 (0%) 1/79 (1.3%)
    Respiratory tract infection2/79 (2.5%) 0/78 (0%) 1/79 (1.3%)
    Sepsis0/79 (0%) 0/78 (0%) 1/79 (1.3%)
    Septic shock0/79 (0%) 1/78 (1.3%) 1/79 (1.3%)
    Upper respiratory tract infection0/79 (0%) 2/78 (2.6%) 0/79 (0%)
    Urinary tract infection1/79 (1.3%) 0/78 (0%) 0/79 (0%)
    Injury, poisoning and procedural complications
    Femur fracture0/79 (0%) 1/78 (1.3%) 0/79 (0%)
    Postoperative fever0/79 (0%) 1/78 (1.3%) 0/79 (0%)
    Procedural pneumothorax0/79 (0%) 1/78 (1.3%) 0/79 (0%)
    Investigations
    Blood glucose increased1/79 (1.3%) 0/78 (0%) 0/79 (0%)
    Blood sodium decreased0/79 (0%) 1/78 (1.3%) 0/79 (0%)
    Liver function test abnormal0/79 (0%) 1/78 (1.3%) 0/79 (0%)
    White blood cell count increased0/79 (0%) 1/78 (1.3%) 0/79 (0%)
    Metabolism and nutrition disorders
    Decreased appetite1/79 (1.3%) 0/78 (0%) 0/79 (0%)
    Hyponatraemia0/79 (0%) 1/78 (1.3%) 0/79 (0%)
    Metabolic alkalosis0/79 (0%) 0/78 (0%) 1/79 (1.3%)
    Musculoskeletal and connective tissue disorders
    Arthralgia0/79 (0%) 0/78 (0%) 1/79 (1.3%)
    Back pain2/79 (2.5%) 0/78 (0%) 1/79 (1.3%)
    Muscular weakness0/79 (0%) 1/78 (1.3%) 0/79 (0%)
    Pain in extremity0/79 (0%) 1/78 (1.3%) 0/79 (0%)
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Cancer pain1/79 (1.3%) 0/78 (0%) 0/79 (0%)
    Metastases to meninges1/79 (1.3%) 0/78 (0%) 0/79 (0%)
    Nervous system disorders
    Aphasia0/79 (0%) 1/78 (1.3%) 0/79 (0%)
    Balance disorder0/79 (0%) 1/78 (1.3%) 0/79 (0%)
    Cerebrovascular accident0/79 (0%) 1/78 (1.3%) 0/79 (0%)
    Epilepsy0/79 (0%) 0/78 (0%) 2/79 (2.5%)
    Generalised tonic-clonic seizure1/79 (1.3%) 0/78 (0%) 0/79 (0%)
    Headache1/79 (1.3%) 1/78 (1.3%) 0/79 (0%)
    Hemiparesis1/79 (1.3%) 0/78 (0%) 0/79 (0%)
    Paraparesis1/79 (1.3%) 0/78 (0%) 0/79 (0%)
    Seizure0/79 (0%) 1/78 (1.3%) 0/79 (0%)
    Spinal cord compression0/79 (0%) 0/78 (0%) 1/79 (1.3%)
    Psychiatric disorders
    Confusional state1/79 (1.3%) 1/78 (1.3%) 0/79 (0%)
    Renal and urinary disorders
    Acute kidney injury1/79 (1.3%) 0/78 (0%) 1/79 (1.3%)
    Dysuria0/79 (0%) 0/78 (0%) 1/79 (1.3%)
    Haematuria1/79 (1.3%) 0/78 (0%) 0/79 (0%)
    Urinary tract obstruction1/79 (1.3%) 0/78 (0%) 0/79 (0%)
    Respiratory, thoracic and mediastinal disorders
    Acute respiratory distress syndrome1/79 (1.3%) 0/78 (0%) 0/79 (0%)
    Chronic obstructive pulmonary disease0/79 (0%) 1/78 (1.3%) 0/79 (0%)
    Dyspnoea4/79 (5.1%) 1/78 (1.3%) 4/79 (5.1%)
    Hypoxia0/79 (0%) 1/78 (1.3%) 0/79 (0%)
    Interstitial lung disease1/79 (1.3%) 0/78 (0%) 0/79 (0%)
    Pleural effusion2/79 (2.5%) 0/78 (0%) 4/79 (5.1%)
    Pneumonitis0/79 (0%) 2/78 (2.6%) 1/79 (1.3%)
    Pneumothorax spontaneous0/79 (0%) 0/78 (0%) 1/79 (1.3%)
    Pulmonary embolism3/79 (3.8%) 3/78 (3.8%) 1/79 (1.3%)
    Pulmonary haemorrhage0/79 (0%) 2/78 (2.6%) 0/79 (0%)
    Respiratory distress1/79 (1.3%) 0/78 (0%) 0/79 (0%)
    Respiratory failure0/79 (0%) 3/78 (3.8%) 0/79 (0%)
    Vascular disorders
    Circulatory collapse1/79 (1.3%) 0/78 (0%) 0/79 (0%)
    Deep vein thrombosis0/79 (0%) 1/78 (1.3%) 0/79 (0%)
    Orthostatic hypotension0/79 (0%) 1/78 (1.3%) 0/79 (0%)
    Other (Not Including Serious) Adverse Events
    Nab-Paclitaxel + CC-486 Combination ArmNab-Paclitaxel + Durvalumab Combination ArmNab-Paclitaxel Monotherapy Arm
    Affected / at Risk (%)# EventsAffected / at Risk (%)# EventsAffected / at Risk (%)# Events
    Total78/79 (98.7%) 76/78 (97.4%) 78/79 (98.7%)
    Blood and lymphatic system disorders
    Anaemia12/79 (15.2%) 23/78 (29.5%) 24/79 (30.4%)
    Leukopenia5/79 (6.3%) 1/78 (1.3%) 3/79 (3.8%)
    Neutropenia15/79 (19%) 14/78 (17.9%) 10/79 (12.7%)
    Ear and labyrinth disorders
    Vertigo4/79 (5.1%) 2/78 (2.6%) 3/79 (3.8%)
    Endocrine disorders
    Hypothyroidism0/79 (0%) 5/78 (6.4%) 0/79 (0%)
    Eye disorders
    Vision blurred4/79 (5.1%) 1/78 (1.3%) 0/79 (0%)
    Gastrointestinal disorders
    Abdominal pain7/79 (8.9%) 3/78 (3.8%) 8/79 (10.1%)
    Abdominal pain upper3/79 (3.8%) 4/78 (5.1%) 2/79 (2.5%)
    Constipation32/79 (40.5%) 20/78 (25.6%) 26/79 (32.9%)
    Diarrhoea33/79 (41.8%) 27/78 (34.6%) 19/79 (24.1%)
    Dyspepsia5/79 (6.3%) 4/78 (5.1%) 6/79 (7.6%)
    Haemorrhoids4/79 (5.1%) 1/78 (1.3%) 0/79 (0%)
    Nausea45/79 (57%) 18/78 (23.1%) 20/79 (25.3%)
    Stomatitis8/79 (10.1%) 6/78 (7.7%) 8/79 (10.1%)
    Vomiting42/79 (53.2%) 10/78 (12.8%) 17/79 (21.5%)
    General disorders
    Asthenia26/79 (32.9%) 36/78 (46.2%) 25/79 (31.6%)
    Chills0/79 (0%) 2/78 (2.6%) 4/79 (5.1%)
    Fatigue24/79 (30.4%) 22/78 (28.2%) 23/79 (29.1%)
    General physical health deterioration4/79 (5.1%) 4/78 (5.1%) 1/79 (1.3%)
    Non-cardiac chest pain3/79 (3.8%) 5/78 (6.4%) 5/79 (6.3%)
    Oedema peripheral12/79 (15.2%) 11/78 (14.1%) 15/79 (19%)
    Pyrexia10/79 (12.7%) 13/78 (16.7%) 7/79 (8.9%)
    Infections and infestations
    Bronchitis2/79 (2.5%) 1/78 (1.3%) 4/79 (5.1%)
    Lower respiratory tract infection1/79 (1.3%) 11/78 (14.1%) 3/79 (3.8%)
    Nasopharyngitis5/79 (6.3%) 4/78 (5.1%) 5/79 (6.3%)
    Oral candidiasis5/79 (6.3%) 3/78 (3.8%) 4/79 (5.1%)
    Respiratory tract infection2/79 (2.5%) 9/78 (11.5%) 4/79 (5.1%)
    Upper respiratory tract infection3/79 (3.8%) 20/78 (25.6%) 8/79 (10.1%)
    Urinary tract infection2/79 (2.5%) 10/78 (12.8%) 4/79 (5.1%)
    Investigations
    Alanine aminotransferase increased2/79 (2.5%) 4/78 (5.1%) 0/79 (0%)
    Blood creatinine increased0/79 (0%) 4/78 (5.1%) 1/79 (1.3%)
    Neutrophil count decreased5/79 (6.3%) 0/78 (0%) 4/79 (5.1%)
    Weight decreased9/79 (11.4%) 2/78 (2.6%) 5/79 (6.3%)
    Metabolism and nutrition disorders
    Decreased appetite27/79 (34.2%) 26/78 (33.3%) 24/79 (30.4%)
    Hypomagnesaemia2/79 (2.5%) 5/78 (6.4%) 6/79 (7.6%)
    Hyponatraemia1/79 (1.3%) 4/78 (5.1%) 2/79 (2.5%)
    Hypophosphataemia3/79 (3.8%) 2/78 (2.6%) 4/79 (5.1%)
    Musculoskeletal and connective tissue disorders
    Arthralgia11/79 (13.9%) 9/78 (11.5%) 14/79 (17.7%)
    Back pain4/79 (5.1%) 9/78 (11.5%) 7/79 (8.9%)
    Muscle spasms5/79 (6.3%) 1/78 (1.3%) 3/79 (3.8%)
    Muscular weakness4/79 (5.1%) 1/78 (1.3%) 1/79 (1.3%)
    Musculoskeletal chest pain3/79 (3.8%) 4/78 (5.1%) 1/79 (1.3%)
    Musculoskeletal pain7/79 (8.9%) 6/78 (7.7%) 5/79 (6.3%)
    Myalgia9/79 (11.4%) 4/78 (5.1%) 7/79 (8.9%)
    Neck pain0/79 (0%) 4/78 (5.1%) 7/79 (8.9%)
    Pain in extremity6/79 (7.6%) 4/78 (5.1%) 7/79 (8.9%)
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Cancer pain2/79 (2.5%) 9/78 (11.5%) 4/79 (5.1%)
    Nervous system disorders
    Dizziness8/79 (10.1%) 3/78 (3.8%) 9/79 (11.4%)
    Headache9/79 (11.4%) 8/78 (10.3%) 10/79 (12.7%)
    Paraesthesia10/79 (12.7%) 1/78 (1.3%) 3/79 (3.8%)
    Peripheral motor neuropathy0/79 (0%) 3/78 (3.8%) 5/79 (6.3%)
    Peripheral sensory neuropathy19/79 (24.1%) 23/78 (29.5%) 22/79 (27.8%)
    Psychiatric disorders
    Anxiety5/79 (6.3%) 2/78 (2.6%) 4/79 (5.1%)
    Depressed mood0/79 (0%) 4/78 (5.1%) 1/79 (1.3%)
    Insomnia9/79 (11.4%) 6/78 (7.7%) 8/79 (10.1%)
    Respiratory, thoracic and mediastinal disorders
    Cough16/79 (20.3%) 19/78 (24.4%) 21/79 (26.6%)
    Dyspnoea16/79 (20.3%) 19/78 (24.4%) 22/79 (27.8%)
    Epistaxis3/79 (3.8%) 5/78 (6.4%) 7/79 (8.9%)
    Haemoptysis4/79 (5.1%) 6/78 (7.7%) 6/79 (7.6%)
    Pleural effusion6/79 (7.6%) 1/78 (1.3%) 1/79 (1.3%)
    Productive cough3/79 (3.8%) 10/78 (12.8%) 5/79 (6.3%)
    Pulmonary embolism7/79 (8.9%) 2/78 (2.6%) 2/79 (2.5%)
    Rhinorrhoea2/79 (2.5%) 4/78 (5.1%) 3/79 (3.8%)
    Skin and subcutaneous tissue disorders
    Alopecia25/79 (31.6%) 25/78 (32.1%) 21/79 (26.6%)
    Dry skin6/79 (7.6%) 3/78 (3.8%) 3/79 (3.8%)
    Rash erythematous0/79 (0%) 4/78 (5.1%) 0/79 (0%)
    Vascular disorders
    Flushing1/79 (1.3%) 0/78 (0%) 4/79 (5.1%)
    Hypotension2/79 (2.5%) 3/78 (3.8%) 4/79 (5.1%)

    Limitations/Caveats

    [Not Specified]

    More Information

    Certain Agreements

    Principal Investigators are NOT employed by the organization sponsoring the study.

    Results from a center cannot be submitted for publication before results of multicenter study are published unless it is more than one year since study completion.Then, Investigator can publish if manuscript is submitted to Celgene 60 days prior to submission. If Celgene decides publication would hinder drug development, Investigator must delay submission for up to ninety days. Investigator must delete confidential information before submission or defer publication to permit patent applications.

    Results Point of Contact

    Name/TitleAnne McClain, Senior Manager, Clinical Trial Disclosure
    OrganizationCelgene Corporation
    Phone1-888-260-1599
    EmailClinicalTrialDisclosure@Celgene.com
    Responsible Party:
    Celgene
    ClinicalTrials.gov Identifier:
    NCT02250326
    Other Study ID Numbers:
    • ABI-007-NSCL-006
    • 2014-001105-41
    First Posted:
    Sep 26, 2014
    Last Update Posted:
    May 5, 2021
    Last Verified:
    Apr 1, 2021