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)
• Enrollment: 240
• Locations: 34
• Arms: 3
• Anticipated Duration (Months): 95.8
• Patients Per Site: 7.1
• Patients Per Site Per Month: 0.1

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 Disease	Intervention/Treatment	Phase
Carcinoma, Non-Small-Cell Lung	Drug: nab-paclitaxel IV; Drug: CC-486; Drug: Duravalumab	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, 2022

Arms and Interventions

Arm	Intervention/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

	Site	City	State	Country	Postal Code
1	University of California San Francisco	San Francisco	California	United States	94143
2	Hospital of Central Connecticut Gynecologic Oncology	New Britain	Connecticut	United States	06050
3	University Cancer and Blood Center, LLC	Athens	Georgia	United States	30607
4	Washington University	Saint Louis	Missouri	United States	63110
5	John Theurer Cancer Center at Hackensack University Medical Center	Hackensack	New Jersey	United States	07601
6	Weill Cornell Medical College - New York - Presbyterian Hospital	New York	New York	United States	10065
7	Penn State Milton S Hershey Medical Center	Hershey	Pennsylvania	United States	17033
8	Associates in Oncology and Hematology	Chattanooga	Tennessee	United States	37421
9	Millennium Oncology	Houston	Texas	United States	77090
10	Ottawa Hospital Riverside Campus	Ottawa	Ontario	Canada	K1H 8L6
11	Royal Victoria Hospital McGill Department of Oncology(RVH)	Montreal	Quebec	Canada	H3A 1A1
12	Hopital Calmette	Lille		France	59037
13	Centre Rene Gauducheau Centre de Lutte Contre Le Cancer Nantes Atlantique	Saint Herblain		France	44805
14	Hopital Paul Brousse	Villejuif		France	94800
15	Universitatsklinikum Essen	Essen		Germany	45122
16	LungenClinic Grosshansdorf GmbH	Grosshansdorf		Germany	22927
17	Klinik Loewenstein gGmbH	Loewenstein		Germany	74245
18	Azienda Ospedaliero Universitaria Di Bologna - Policlinico S.Orsola Malpighi	Bologna		Italy	40138
19	Azienda Ospedaliero Universitaria di Parma	Parma		Italy	43126
20	Azienda Ospedaliero-Universitaria Santa Maria della Misericordia die Udine	Udine		Italy	33100
21	Hospital Universitario Germans Trias i Pujol	Barcelona		Spain	08916
22	Hospital Universitari Vall d'Hebron	Barcelona		Spain	8035
23	Hospital Universitario Ramon y Cajal	Madrid		Spain	28034
24	Hospital 12 de Octubre	Madrid		Spain	28041
25	Hospital General Carlos Haya	Malaga		Spain	29010
26	Hospital General Universitario de Valencia	Valencia		Spain	46014
27	Hospital Universitari i Politecnic La Fe de Valencia	Valencia		Spain	46026
28	Liverpool Heart and Chest Hospital	Bebington, Wirral		United Kingdom	CH63 4JY
29	Heart of England NHS Foundation Trust	Birmingham		United Kingdom	B9 5SS
30	Sarah Cannon Research Institute UK	London		United Kingdom	NW1 2BU
31	Charing Cross Hospital	London		United Kingdom	W6 8RF
32	University Hospital of South Manchester NHS Foundation Trust -Wythenshawe Hospital - North West Lung	Manchester		United Kingdom	M23 9LT
33	Newcastle Hospital	Newcastle Upon Tyne		United Kingdom	NE7 7DN
34	Churchhill Hospital	Oxford		United Kingdom	OX3 7LI

Sponsors and Collaborators

• Celgene

Investigators

• Study Director: Bristol-Myers Squibb, Bristol-Myers Squibb

Study Documents (Full-Text)

• Study Protocol: ABI_007-NSCL_Protocol_AM5_Redacted_09December 2016 - Dec 9, 2016
• Study Protocol: ABI-007-NSCL-006_Protocol_AM4_Redacted.31May2016 - May 31, 2016
• Study Protocol: ABI_007-NSCL_Protocol_AM3_Redacted_14 April 2016 - Apr 14, 2016
• Study Protocol: ABI_007-NSCL_Protocol_AM2_Redacted_18July2014 - Jul 18, 2014
• Study Protocol: ABI_007-NSCL_Protocol_AM1_Redacted_24 June 2014 - Jun 24, 2014
• Study Protocol: ABI_007-NSCL_Protocol_Original_Redacted_29May2014 - May 29, 2014
• Statistical Analysis Plan - Aug 25, 2016

More Information

Publications

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• Barnes JA, Ellis ML, Hwang S, Emarine J, Merwin P, Salinas GD, Musher BL. Identification of Educational Gaps Among Oncologists Who Manage Patients with Pancreatic Cancer. J Gastrointest Cancer. 2019 Mar;50(1):84-90. doi: 10.1007/s12029-017-0033-8.
• Cartwright TH, Parisi M, Espirito JL, Wilson TW, Pelletier C, Patel M, Babiker HM. Clinical Outcomes with First-Line Chemotherapy in a Large Retrospective Study of Patients with Metastatic Pancreatic Cancer Treated in a US Community Oncology Setting. Drugs Real World Outcomes. 2018 Sep;5(3):149-159. doi: 10.1007/s40801-018-0137-x.
• Cristea MC, Frankel P, Synold T, Rivkin S, Lim D, Chung V, Chao J, Wakabayashi M, Paz B, Han E, Lin P, Leong L, Hakim A, Carroll M, Prakash N, Dellinger T, Park M, Morgan RJ. A phase I trial of intraperitoneal nab-paclitaxel in the treatment of advanced malignancies primarily confined to the peritoneal cavity. Cancer Chemother Pharmacol. 2019 Mar;83(3):589-598. doi: 10.1007/s00280-019-03767-9. Epub 2019 Jan 8.
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• Fernández A, Salgado M, García A, Buxò E, Vera R, Adeva J, Jiménez-Fonseca P, Quintero G, Llorca C, Cañabate M, López LJ, Muñoz A, Ramírez P, González P, López C, Reboredo M, Gallardo E, Sanchez-Cánovas M, Gallego J, Guillén C, Ruiz-Miravet N, Navarro-Pérez V, De la Cámara J, Alés-Díaz I, Pazo-Cid RA, Carmona-Bayonas A. Prognostic factors for survival with nab-paclitaxel plus gemcitabine in metastatic pancreatic cancer in real-life practice: the ANICE-PaC study. BMC Cancer. 2018 Nov 29;18(1):1185. doi: 10.1186/s12885-018-5101-3.
• Gajra A, Karim NA, Mulford DA, Villaruz LC, Matrana MR, Ali HY, Santos ES, Berry T, Ong TJ, Sanford A, Amiri K, Spigel DR. nab-Paclitaxel-Based Therapy in Underserved Patient Populations: The ABOUND.PS2 Study in Patients With NSCLC and a Performance Status of 2. Front Oncol. 2018 Jul 24;8:253. doi: 10.3389/fonc.2018.00253. eCollection 2018.
• Hegewisch-Becker S, Aldaoud A, Wolf T, Krammer-Steiner B, Linde H, Scheiner-Sparna R, Hamm D, Jänicke M, Marschner N; TPK-Group (Tumour Registry Pancreatic Cancer). Results from the prospective German TPK clinical cohort study: Treatment algorithms and survival of 1,174 patients with locally advanced, inoperable, or metastatic pancreatic ductal adenocarcinoma. Int J Cancer. 2019 Mar 1;144(5):981-990. doi: 10.1002/ijc.31751. Epub 2018 Oct 3.
• Hurria A, Soto-Perez-de-Celis E, Blanchard S, Burhenn P, Yeon CH, Yuan Y, Li D, Katheria V, Waisman JR, Luu TH, Somlo G, Noonan AM, Lee T, Sudan N, Chung S, Rotter A, Arsenyan A, Levi A, Choi J, Rubalcava A, Morrison R, Mortimer JE. A Phase II Trial of Older Adults With Metastatic Breast Cancer Receiving nab-Paclitaxel: Melding the Fields of Geriatrics and Oncology. Clin Breast Cancer. 2019 Apr;19(2):89-96. doi: 10.1016/j.clbc.2018.10.002. Epub 2018 Oct 16.
• Kim S, Signorovitch JE, Yang H, Patterson-Lomba O, Xiang CQ, Ung B, Parisi M, Marshall JL. Comparative Effectiveness of nab-Paclitaxel Plus Gemcitabine vs FOLFIRINOX in Metastatic Pancreatic Cancer: A Retrospective Nationwide Chart Review in the United States. Adv Ther. 2018 Oct;35(10):1564-1577. doi: 10.1007/s12325-018-0784-z. Epub 2018 Sep 12.
• Langer CJ, Kim ES, Anderson EC, Jotte RM, Modiano M, Haggstrom DE, Socoteanu MP, Smith DA, Dakhil C, Konduri K, Berry T, Ong TJ, Sanford A, Amiri K, Goldman JW, Weiss J; ABOUND.70+ Investigators. nab-Paclitaxel-Based Therapy in Underserved Patient Populations: The ABOUND.70+ Study in Elderly Patients With Advanced NSCLC. Front Oncol. 2018 Jul 24;8:262. doi: 10.3389/fonc.2018.00262. eCollection 2018.
• Li F, Yuan H, Zhang H, He M, Liao J, Chen N, Li Y, Zhou S, Palmisano M, Yu A, Pai M, Sun D. Neonatal Fc Receptor (FcRn) Enhances Tissue Distribution and Prevents Excretion of nab-Paclitaxel. Mol Pharm. 2019 Jun 3;16(6):2385-2393. doi: 10.1021/acs.molpharmaceut.8b01314. Epub 2019 May 1.
• Li F, Zhang H, He M, Liao J, Chen N, Li Y, Zhou S, Palmisano M, Yu A, Pai MP, Yuan H, Sun D. Different Nanoformulations Alter the Tissue Distribution of Paclitaxel, Which Aligns with Reported Distinct Efficacy and Safety Profiles. Mol Pharm. 2018 Oct 1;15(10):4505-4516. doi: 10.1021/acs.molpharmaceut.8b00527. Epub 2018 Sep 21.
• Li YF, Zhang C, Zhou S, He M, Zhang H, Chen N, Li F, Luan X, Pai M, Yuan H, Sun D, Li Y. Species difference in paclitaxel disposition correlated with poor pharmacological efficacy translation from mice to humans. Clin Pharmacol. 2018 Nov 8;10:165-174. doi: 10.2147/CPAA.S185449. eCollection 2018.
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• 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: Jan 31, 2022
• Last Verified: Jan 1, 2022

• Keywords provided by Celgene: Cancer of the lung; lung neoplasm; NSCLC - non-small cell lung cancer; Nonsquamou; squamous; squamous NSCLC; Tumor; locally advanced NSCLC; metastatic NSCLC; advanced lung cancer; metastatic lung cancer; non-squamous NSCLC; lung cancer; Abraxane; ABI-007; nab-paclitaxel; albumin-bound paclitaxel; taxanes; CC-486; oral azacitidine; azacitidine; second line treatment of lung cancer; second line treatment; Celgene; abound.2L; third line treatment; durvalumab; immunotherapy; MEDI4736
• Additional relevant MeSH terms: Lung Neoplasms; Carcinoma, Non-Small-Cell Lung; Paclitaxel; Azacitidine; Cc-486

Study Results

Participant Flow

Recruitment Details	This was a multicenter study with 34 sites from the United States, Canada, France, Germany, Italy, Spain and the United Kingdom.
Pre-assignment Detail	Eligible 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 Title	Nab-Paclitaxel + CC-486 Combination Arm	Nab-Paclitaxel + Durvalumab Combination Arm	Nab-Paclitaxel Monotherapy Arm
Arm/Group Description	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.	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
STARTED	81	79	80
Treated Population	79	78	79
COMPLETED	0	15	3
NOT COMPLETED	81	64	77
Period Title: Treatment Period
STARTED	67	43	64
COMPLETED	18	13	26
NOT COMPLETED	49	30	38

Baseline Characteristics

Arm/Group Title	Nab-Paclitaxel + CC-486 Combination Arm	Nab-Paclitaxel + Durvalumab Combination Arm	Nab-Paclitaxel Monotherapy Arm	Total
Arm/Group Description	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.	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 Participants	81	79	80	240
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

Title	Kaplan Meier Estimate of Progression-Free Survival (PFS) as Assessed by the Investigator
Description	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.
Time Frame	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

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 Title	Nab-Paclitaxel + CC-486 Combination Arm	Nab-Paclitaxel + Durvalumab Combination Arm	Nab-Paclitaxel Alone
Arm/Group Description	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.	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 Participants	81	79	80
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 Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	1.3
	Confidence Interval	(2-Sided) 95%; 0.90 to 1.94
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Secondary Outcome

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

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 Title	Nab-Paclitaxel + CC-486 Combination Arm	Nab-Paclitaxel + Durvalumab Combination Arm	Nab-Paclitaxel Alone
Arm/Group Description	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.	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 Participants	81	79	80
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 Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Disease Control Rate Ratio
	Estimated Value	0.97
	Confidence Interval	(2-Sided) 95%; 0.778 to 1.207
	Parameter Dispersion	Type: Value:
	Estimation Comments	95% CI was calculated using Clopper-Pearson method.
Other Statistical Analysis		Direction of Disease Control Rate Ratio is DCR of Nab-Paclitaxel + CC-486 Combination Arm over DCR of Nab-Paclitaxel Alone

3. Secondary Outcome

Title	Percentage of Participants Who Achieved a Best Overall Response of Complete Response or Partial Response According to RECIST V 1.1 Criteria
Description	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.
Time Frame	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

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 Title	Nab-Paclitaxel + CC-486 Combination Arm	Nab-Paclitaxel + Durvalumab Combination Arm	Nab-Paclitaxel Alone
Arm/Group Description	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.	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 Participants	81	79	80
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 Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Overall Response Rate Ratio
	Estimated Value	0.84
	Confidence Interval	(2-Sided) 95%; 0.398 to 1.754
	Parameter Dispersion	Type: Value:
	Estimation Comments	95% CI was calculated using Clopper-Pearson method.
Other Statistical Analysis		Direction of Overall Response Rate Ratio is ORR of Nab-Paclitaxel + CC-486 Combination Arm over ORR of nab-Paclitaxel Alone.

4. Secondary Outcome

Title	Kaplan Meier Estimate of Overall Survival (OS)
Description	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.
Time Frame	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

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 Title	Nab-Paclitaxel + CC-486 Combination Arm	Nab-Paclitaxel + Durvalumab Combination Arm	Nab-Paclitaxel Alone
Arm/Group Description	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.	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 Participants	81	79	80
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 Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	1.7
	Confidence Interval	(2-Sided) 95%; 1.08 to 2.57
	Parameter Dispersion	Type: Value:
	Estimation Comments

5. Secondary Outcome

Title	Number of Participants With Treatment Emergent Adverse Events (TEAEs) During the Entire Treatment Period
Description	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.
Time Frame	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

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 Title	Nab-Paclitaxel + CC-486 Combination Arm	Nab-Paclitaxel + Durvalumab Combination Arm	Nab-Paclitaxel Alone
Arm/Group Description	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.	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 Participants	79	78	79
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

Title	Percentage of Participants Who Discontinued Study Treatment
Description	The discontinuation rate was defined as the percentage of participants who had study drug discontinued and was assessed throughout the conduct of the study.
Time Frame	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

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 Title	Nab-Paclitaxel + CC-486 Combination Arm	Nab-Paclitaxel + Durvalumab Combination Arm	Nab-Paclitaxel Alone
Arm/Group Description	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.	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 Participants	79	79	80
Number [percentage of participants]	100.0 123.5%	80.8 102.3%	96.2 120.3%

7. Secondary Outcome

Title	Dose Intensity Per Week of Nab-Paclitaxel
Description	Dose intensity was the cumulative dose divided by the dosing period in weeks.
Time Frame	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

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 Title	Nab-Paclitaxel + CC-486 Combination Arm	Nab-Paclitaxel + Durvalumab Combination Arm	Nab-Paclitaxel Alone
Arm/Group Description	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.	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 Participants	79	78	79
Mean (Standard Deviation) [mg/m^2/week]	54.73 (11.390)	57.18 (13.605)	58.61 (14.893)

8. Secondary Outcome

Title	Dose Intensity Per Week of CC-486
Description	Dose intensity was the cumulative dose divided by the dosing period in weeks.
Time Frame	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

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 Title	Nab-Paclitaxel + CC-486 Combination Arm
Arm/Group Description	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.
Measure Participants	79
Mean (Standard Deviation) [mg/ week]	716.66 (220.945)

9. Secondary Outcome

Title	Dose Intensity Per Week of Durvalumab
Description	Dose intensity was the cumulative dose divided by the dosing period in weeks).
Time Frame	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

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 Title	Nab-Paclitaxel + Durvalumab Combination Arm
Arm/Group Description	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.
Measure Participants	77
Mean (Standard Deviation) [mg/week]	279.96 (97.304)

10. Secondary Outcome

Title	Percentage of Participants With Study Drug Dose Reductions
Description	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.
Time Frame	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

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 Title	Nab-Paclitaxel + CC-486 Combination Arm	Nab-Paclitaxel + Durvalumab Combination Arm	Nab-Paclitaxel Alone
Arm/Group Description	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.	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 Participants	79	78	79
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 Frame	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
Arm/Group Title	Nab-Paclitaxel + CC-486 Combination Arm		Nab-Paclitaxel + Durvalumab Combination Arm		Nab-Paclitaxel Monotherapy Arm
Arm/Group Description	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.		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 Arm		Nab-Paclitaxel + Durvalumab Combination Arm		Nab-Paclitaxel Monotherapy Arm
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	53/81 (65.4%)		44/79 (55.7%)		37/80 (46.3%)
Serious Adverse Events
	Nab-Paclitaxel + CC-486 Combination Arm		Nab-Paclitaxel + Durvalumab Combination Arm		Nab-Paclitaxel Monotherapy Arm
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	30/79 (38%)		37/78 (47.4%)		29/79 (36.7%)
Blood and lymphatic system disorders
Anaemia	0/79 (0%)		1/78 (1.3%)		0/79 (0%)
Febrile neutropenia	1/79 (1.3%)		0/78 (0%)		0/79 (0%)
Cardiac disorders
Atrial fibrillation	0/79 (0%)		1/78 (1.3%)		0/79 (0%)
Cardiac failure	0/79 (0%)		0/78 (0%)		1/79 (1.3%)
Endocrine disorders
Adrenal insufficiency	0/79 (0%)		3/78 (3.8%)		0/79 (0%)
Gastrointestinal disorders
Abdominal pain	2/79 (2.5%)		0/78 (0%)		0/79 (0%)
Diarrhoea	1/79 (1.3%)		1/78 (1.3%)		0/79 (0%)
Duodenal obstruction	0/79 (0%)		0/78 (0%)		1/79 (1.3%)
Flatulence	1/79 (1.3%)		0/78 (0%)		0/79 (0%)
Intestinal obstruction	1/79 (1.3%)		0/78 (0%)		0/79 (0%)
Nausea	1/79 (1.3%)		1/78 (1.3%)		1/79 (1.3%)
Vomiting	2/79 (2.5%)		1/78 (1.3%)		1/79 (1.3%)
General disorders
Death	0/79 (0%)		1/78 (1.3%)		0/79 (0%)
General physical health deterioration	2/79 (2.5%)		2/78 (2.6%)		1/79 (1.3%)
Performance status decreased	2/79 (2.5%)		1/78 (1.3%)		0/79 (0%)
Pyrexia	3/79 (3.8%)		2/78 (2.6%)		1/79 (1.3%)
Sudden death	1/79 (1.3%)		0/78 (0%)		0/79 (0%)
Infections and infestations
Abdominal wall abscess	1/79 (1.3%)		0/78 (0%)		0/79 (0%)
Bronchitis	1/79 (1.3%)		0/78 (0%)		0/79 (0%)
Cellulitis	0/79 (0%)		1/78 (1.3%)		0/79 (0%)
Infection	0/79 (0%)		0/78 (0%)		1/79 (1.3%)
Influenza	1/79 (1.3%)		0/78 (0%)		0/79 (0%)
Lower respiratory tract infection	1/79 (1.3%)		2/78 (2.6%)		1/79 (1.3%)
Lung infection	0/79 (0%)		1/78 (1.3%)		0/79 (0%)
Pneumocystis jirovecii pneumonia	0/79 (0%)		1/78 (1.3%)		0/79 (0%)
Pneumonia	5/79 (6.3%)		8/78 (10.3%)		3/79 (3.8%)
Pneumonia pneumococcal	1/79 (1.3%)		0/78 (0%)		0/79 (0%)
Postoperative wound infection	0/79 (0%)		0/78 (0%)		1/79 (1.3%)
Respiratory tract infection	2/79 (2.5%)		0/78 (0%)		1/79 (1.3%)
Sepsis	0/79 (0%)		0/78 (0%)		1/79 (1.3%)
Septic shock	0/79 (0%)		1/78 (1.3%)		1/79 (1.3%)
Upper respiratory tract infection	0/79 (0%)		2/78 (2.6%)		0/79 (0%)
Urinary tract infection	1/79 (1.3%)		0/78 (0%)		0/79 (0%)
Injury, poisoning and procedural complications
Femur fracture	0/79 (0%)		1/78 (1.3%)		0/79 (0%)
Postoperative fever	0/79 (0%)		1/78 (1.3%)		0/79 (0%)
Procedural pneumothorax	0/79 (0%)		1/78 (1.3%)		0/79 (0%)
Investigations
Blood glucose increased	1/79 (1.3%)		0/78 (0%)		0/79 (0%)
Blood sodium decreased	0/79 (0%)		1/78 (1.3%)		0/79 (0%)
Liver function test abnormal	0/79 (0%)		1/78 (1.3%)		0/79 (0%)
White blood cell count increased	0/79 (0%)		1/78 (1.3%)		0/79 (0%)
Metabolism and nutrition disorders
Decreased appetite	1/79 (1.3%)		0/78 (0%)		0/79 (0%)
Hyponatraemia	0/79 (0%)		1/78 (1.3%)		0/79 (0%)
Metabolic alkalosis	0/79 (0%)		0/78 (0%)		1/79 (1.3%)
Musculoskeletal and connective tissue disorders
Arthralgia	0/79 (0%)		0/78 (0%)		1/79 (1.3%)
Back pain	2/79 (2.5%)		0/78 (0%)		1/79 (1.3%)
Muscular weakness	0/79 (0%)		1/78 (1.3%)		0/79 (0%)
Pain in extremity	0/79 (0%)		1/78 (1.3%)		0/79 (0%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Cancer pain	1/79 (1.3%)		0/78 (0%)		0/79 (0%)
Metastases to meninges	1/79 (1.3%)		0/78 (0%)		0/79 (0%)
Nervous system disorders
Aphasia	0/79 (0%)		1/78 (1.3%)		0/79 (0%)
Balance disorder	0/79 (0%)		1/78 (1.3%)		0/79 (0%)
Cerebrovascular accident	0/79 (0%)		1/78 (1.3%)		0/79 (0%)
Epilepsy	0/79 (0%)		0/78 (0%)		2/79 (2.5%)
Generalised tonic-clonic seizure	1/79 (1.3%)		0/78 (0%)		0/79 (0%)
Headache	1/79 (1.3%)		1/78 (1.3%)		0/79 (0%)
Hemiparesis	1/79 (1.3%)		0/78 (0%)		0/79 (0%)
Paraparesis	1/79 (1.3%)		0/78 (0%)		0/79 (0%)
Seizure	0/79 (0%)		1/78 (1.3%)		0/79 (0%)
Spinal cord compression	0/79 (0%)		0/78 (0%)		1/79 (1.3%)
Psychiatric disorders
Confusional state	1/79 (1.3%)		1/78 (1.3%)		0/79 (0%)
Renal and urinary disorders
Acute kidney injury	1/79 (1.3%)		0/78 (0%)		1/79 (1.3%)
Dysuria	0/79 (0%)		0/78 (0%)		1/79 (1.3%)
Haematuria	1/79 (1.3%)		0/78 (0%)		0/79 (0%)
Urinary tract obstruction	1/79 (1.3%)		0/78 (0%)		0/79 (0%)
Respiratory, thoracic and mediastinal disorders
Acute respiratory distress syndrome	1/79 (1.3%)		0/78 (0%)		0/79 (0%)
Chronic obstructive pulmonary disease	0/79 (0%)		1/78 (1.3%)		0/79 (0%)
Dyspnoea	4/79 (5.1%)		1/78 (1.3%)		4/79 (5.1%)
Hypoxia	0/79 (0%)		1/78 (1.3%)		0/79 (0%)
Interstitial lung disease	1/79 (1.3%)		0/78 (0%)		0/79 (0%)
Pleural effusion	2/79 (2.5%)		0/78 (0%)		4/79 (5.1%)
Pneumonitis	0/79 (0%)		2/78 (2.6%)		1/79 (1.3%)
Pneumothorax spontaneous	0/79 (0%)		0/78 (0%)		1/79 (1.3%)
Pulmonary embolism	3/79 (3.8%)		3/78 (3.8%)		1/79 (1.3%)
Pulmonary haemorrhage	0/79 (0%)		2/78 (2.6%)		0/79 (0%)
Respiratory distress	1/79 (1.3%)		0/78 (0%)		0/79 (0%)
Respiratory failure	0/79 (0%)		3/78 (3.8%)		0/79 (0%)
Vascular disorders
Circulatory collapse	1/79 (1.3%)		0/78 (0%)		0/79 (0%)
Deep vein thrombosis	0/79 (0%)		1/78 (1.3%)		0/79 (0%)
Orthostatic hypotension	0/79 (0%)		1/78 (1.3%)		0/79 (0%)
Other (Not Including Serious) Adverse Events
	Nab-Paclitaxel + CC-486 Combination Arm		Nab-Paclitaxel + Durvalumab Combination Arm		Nab-Paclitaxel Monotherapy Arm
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	78/79 (98.7%)		76/78 (97.4%)		78/79 (98.7%)
Blood and lymphatic system disorders
Anaemia	12/79 (15.2%)		23/78 (29.5%)		24/79 (30.4%)
Leukopenia	5/79 (6.3%)		1/78 (1.3%)		3/79 (3.8%)
Neutropenia	15/79 (19%)		14/78 (17.9%)		10/79 (12.7%)
Ear and labyrinth disorders
Vertigo	4/79 (5.1%)		2/78 (2.6%)		3/79 (3.8%)
Endocrine disorders
Hypothyroidism	0/79 (0%)		5/78 (6.4%)		0/79 (0%)
Eye disorders
Vision blurred	4/79 (5.1%)		1/78 (1.3%)		0/79 (0%)
Gastrointestinal disorders
Abdominal pain	7/79 (8.9%)		3/78 (3.8%)		8/79 (10.1%)
Abdominal pain upper	3/79 (3.8%)		4/78 (5.1%)		2/79 (2.5%)
Constipation	32/79 (40.5%)		20/78 (25.6%)		26/79 (32.9%)
Diarrhoea	33/79 (41.8%)		27/78 (34.6%)		19/79 (24.1%)
Dyspepsia	5/79 (6.3%)		4/78 (5.1%)		6/79 (7.6%)
Haemorrhoids	4/79 (5.1%)		1/78 (1.3%)		0/79 (0%)
Nausea	45/79 (57%)		18/78 (23.1%)		20/79 (25.3%)
Stomatitis	8/79 (10.1%)		6/78 (7.7%)		8/79 (10.1%)
Vomiting	42/79 (53.2%)		10/78 (12.8%)		17/79 (21.5%)
General disorders
Asthenia	26/79 (32.9%)		36/78 (46.2%)		25/79 (31.6%)
Chills	0/79 (0%)		2/78 (2.6%)		4/79 (5.1%)
Fatigue	24/79 (30.4%)		22/78 (28.2%)		23/79 (29.1%)
General physical health deterioration	4/79 (5.1%)		4/78 (5.1%)		1/79 (1.3%)
Non-cardiac chest pain	3/79 (3.8%)		5/78 (6.4%)		5/79 (6.3%)
Oedema peripheral	12/79 (15.2%)		11/78 (14.1%)		15/79 (19%)
Pyrexia	10/79 (12.7%)		13/78 (16.7%)		7/79 (8.9%)
Infections and infestations
Bronchitis	2/79 (2.5%)		1/78 (1.3%)		4/79 (5.1%)
Lower respiratory tract infection	1/79 (1.3%)		11/78 (14.1%)		3/79 (3.8%)
Nasopharyngitis	5/79 (6.3%)		4/78 (5.1%)		5/79 (6.3%)
Oral candidiasis	5/79 (6.3%)		3/78 (3.8%)		4/79 (5.1%)
Respiratory tract infection	2/79 (2.5%)		9/78 (11.5%)		4/79 (5.1%)
Upper respiratory tract infection	3/79 (3.8%)		20/78 (25.6%)		8/79 (10.1%)
Urinary tract infection	2/79 (2.5%)		10/78 (12.8%)		4/79 (5.1%)
Investigations
Alanine aminotransferase increased	2/79 (2.5%)		4/78 (5.1%)		0/79 (0%)
Blood creatinine increased	0/79 (0%)		4/78 (5.1%)		1/79 (1.3%)
Neutrophil count decreased	5/79 (6.3%)		0/78 (0%)		4/79 (5.1%)
Weight decreased	9/79 (11.4%)		2/78 (2.6%)		5/79 (6.3%)
Metabolism and nutrition disorders
Decreased appetite	27/79 (34.2%)		26/78 (33.3%)		24/79 (30.4%)
Hypomagnesaemia	2/79 (2.5%)		5/78 (6.4%)		6/79 (7.6%)
Hyponatraemia	1/79 (1.3%)		4/78 (5.1%)		2/79 (2.5%)
Hypophosphataemia	3/79 (3.8%)		2/78 (2.6%)		4/79 (5.1%)
Musculoskeletal and connective tissue disorders
Arthralgia	11/79 (13.9%)		9/78 (11.5%)		14/79 (17.7%)
Back pain	4/79 (5.1%)		9/78 (11.5%)		7/79 (8.9%)
Muscle spasms	5/79 (6.3%)		1/78 (1.3%)		3/79 (3.8%)
Muscular weakness	4/79 (5.1%)		1/78 (1.3%)		1/79 (1.3%)
Musculoskeletal chest pain	3/79 (3.8%)		4/78 (5.1%)		1/79 (1.3%)
Musculoskeletal pain	7/79 (8.9%)		6/78 (7.7%)		5/79 (6.3%)
Myalgia	9/79 (11.4%)		4/78 (5.1%)		7/79 (8.9%)
Neck pain	0/79 (0%)		4/78 (5.1%)		7/79 (8.9%)
Pain in extremity	6/79 (7.6%)		4/78 (5.1%)		7/79 (8.9%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Cancer pain	2/79 (2.5%)		9/78 (11.5%)		4/79 (5.1%)
Nervous system disorders
Dizziness	8/79 (10.1%)		3/78 (3.8%)		9/79 (11.4%)
Headache	9/79 (11.4%)		8/78 (10.3%)		10/79 (12.7%)
Paraesthesia	10/79 (12.7%)		1/78 (1.3%)		3/79 (3.8%)
Peripheral motor neuropathy	0/79 (0%)		3/78 (3.8%)		5/79 (6.3%)
Peripheral sensory neuropathy	19/79 (24.1%)		23/78 (29.5%)		22/79 (27.8%)
Psychiatric disorders
Anxiety	5/79 (6.3%)		2/78 (2.6%)		4/79 (5.1%)
Depressed mood	0/79 (0%)		4/78 (5.1%)		1/79 (1.3%)
Insomnia	9/79 (11.4%)		6/78 (7.7%)		8/79 (10.1%)
Respiratory, thoracic and mediastinal disorders
Cough	16/79 (20.3%)		19/78 (24.4%)		21/79 (26.6%)
Dyspnoea	16/79 (20.3%)		19/78 (24.4%)		22/79 (27.8%)
Epistaxis	3/79 (3.8%)		5/78 (6.4%)		7/79 (8.9%)
Haemoptysis	4/79 (5.1%)		6/78 (7.7%)		6/79 (7.6%)
Pleural effusion	6/79 (7.6%)		1/78 (1.3%)		1/79 (1.3%)
Productive cough	3/79 (3.8%)		10/78 (12.8%)		5/79 (6.3%)
Pulmonary embolism	7/79 (8.9%)		2/78 (2.6%)		2/79 (2.5%)
Rhinorrhoea	2/79 (2.5%)		4/78 (5.1%)		3/79 (3.8%)
Skin and subcutaneous tissue disorders
Alopecia	25/79 (31.6%)		25/78 (32.1%)		21/79 (26.6%)
Dry skin	6/79 (7.6%)		3/78 (3.8%)		3/79 (3.8%)
Rash erythematous	0/79 (0%)		4/78 (5.1%)		0/79 (0%)
Vascular disorders
Flushing	1/79 (1.3%)		0/78 (0%)		4/79 (5.1%)
Hypotension	2/79 (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.