Clincosm LogoSign in Get a demo

The BEACON Study (Breast Cancer Outcomes With NKTR-102)

Sponsor
Nektar Therapeutics (Industry)
Overall Status
Completed
CT.gov ID
NCT01492101
Collaborator
(none)
852
Enrollment
153
Locations
2
Arms
54
Duration (Months)
5.6
Patients Per Site
0.1
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The study is designed as an open-label, randomized, parallel, two arm, multicenter, international Phase 3 study in patients with recurrent or metastatic breast cancer previously treated with cytotoxic chemotherapy regimens.

The primary study objective is to compare overall survival of patients who receive NKTR-102 given once every 21 days to patients who receive treatment of Physician's Choice selected from a list of seven single-agent intravenous therapies.

Condition or Disease Intervention/Treatment Phase
Phase 3

Study Design

Study Type:
Interventional
Actual Enrollment :
852 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
The BEACON Study (Breast Cancer Outcomes With NKTR-102): A Phase 3 Open-Label, Randomized, Multicenter Study of NKTR-102 Versus Treatment of Physician's Choice (TPC) in Patients With Locally Recurrent or Metastatic Breast Cancer Previously Treated With an Anthracycline, a Taxane and Capecitabine
Study Start Date :
Dec 1, 2011
Actual Primary Completion Date :
Apr 1, 2016
Actual Study Completion Date :
Jun 1, 2016

Arms and Interventions

Arm Intervention/Treatment
Experimental: NKTR-102

Drug: NKTR-102
145 mg/m2 NKTR-102 will be delivered q21day as a 90-minute intravenous (IV) infusion on day 1 of each treatment cycle.
Active Comparator: Physician's Treatment of Choice

Drug: Treatment of Physician's Choice (TPC)
One of the following Treatment of Physician Choice will be administered per standard of care: eribulin, ixabepilone, vinorelbine, gemcitabine, paclitaxel, docetaxel, or nab-paclitaxel

Outcome Measures

Primary Outcome Measures

  1. Kaplan-Meier Estimate of Overall Survival: Intention to Treat (ITT) Population [36 Months]

    Duration of OS was defined as the time from the date of randomisation to the date of death due to any cause. Subjects were followed until their date of death, loss to follow-up, withdrawal of consent for further follow-up for survival, or final database closure. OS was determined using the ITT population which included all subjects randomized into 1 of the 2 treatment arms. Subjects who were lost-to-follow-up or were not known to have died were censored at last date they were shown to be alive. Subjects who did not have any follow-up since the date of randomization were censored at the date of randomization.

Secondary Outcome Measures

  1. Kaplan-Meier Estimate of Progression-Free Survival (PFS): ITT Population [Up to 38 months.]

    PFS was defined as the time from the date of randomization to the earliest date of disease progression (assessed by the investigator according to RECIST version 1.1) or death due to any cause. PFS was determined using the ITT population which included all subjects randomized into 1 of the 2 treatment arms. For subjects whose disease did not progress or who did not die, the PFS time was censored at the time of the last tumor assessment that demonstrated lack of disease progression. For subjects who received new anti-cancer therapy, the PFS time was censored at the start of the new anti-cancer therapy.

  2. Clinical Benefit Rate (CBR): ITT Population [Up to 38 months.]

    CBR was defined as the proportion of subjects with a CR, PR, or stable disease (SD) for at least 6 months (≥ 182 days).

  3. Duration of Response (DOR): Efficacy Evaluable Population [Up to 38 months.]

    DOR was defined as the time from first documented CR or PR until the earliest evidence of disease progression or death from any cause. Subjects who were alive without documented disease progression per RECIST version 1.1 were censored at the date of last tumor assessment without disease progression or start of new anti-cancer therapy for the study disease.

  4. Incidence of Dose Reductions: Safety Population [Up to 38 months.]

    Proportion of subjects who had a reduction in dose.

  5. Quality of Life Questionnaire-Core 30 (QLQ-C30) Individual Scale, Overall Score: ITT Population [Up to 39 months]

    The QLQ-C30 is composed of 5 multi-item functional scales (physical, role, social, emotional and cognitive functioning), a global health status/QoL scale, 3 symptom scales (fatigue, nausea/vomiting, and pain), and 6 single items (financial impact, appetite loss, diarrhoea, constipation, insomnia and dyspnoea). Most items are scaled 1 to 4 (1 = not at all, 2 = a little, 3 = quite a bit, 4 = very much) except the items contributing to the global health status/QoL, which are 7-point questions (1 = very poor to 7 = excellent). Raw scores were transformed using a linear transformation to standardize the results so that scores range from 0 to 100. n=number of subjects who completed each individual scale. Note that for scores measuring function, a higher score represented a higher "better" level of functioning, while for scores measuring symptoms, a higher score represented a lower "worse" level of symptoms.

  6. QLQ-C30 Individual Scale, Change Over Time: ITT Population [From Baseline to Week 8, Week 16, Week 24, Week 32, Week 40, Week 48, Week 56.]

    The QLQ-C30 is composed of 5 multi-item functional scales (physical, role, social, emotional and cognitive functioning), a global health status/QoL scale, 3 symptom scales (fatigue, nausea/vomiting, and pain), and 6 single items (financial impact, appetite loss, diarrhea, constipation, insomnia and dyspnea). Most items are scaled 1 to 4 (1 = not at all, 2 = a little, 3 = quite a bit, 4 = very much) except the items contributing to the global health status/QoL, which are 7-point questions (from 1 = very poor to 7 = excellent). Raw scores were transformed using a linear transformation to standardize the results so that scores range from 0 to 100. n=number of subjects who completed each individual scale. Note that for scores measuring function, a higher score represented a higher "better" level of functioning, while for scores measuring symptoms, a higher score represented a lower "worse" level of symptoms.

  7. Quality of Life Questionnaire-breast Cancer-specific Module (BR23) Score Value: ITT Population [Baseline]

    The QLQ-BR23 incorporates 5 multi-item scales to assess systemic therapy side effects, arm symptoms, breast symptoms, body image and sexual functioning, and 3 single items to assess sexual enjoyment, upset by hair loss and future perspective. Most items were scaled one to four except the items contributing to the global health status/QoL, which were seven-point questions. Raw scores were transformed using a linear transformation to standardize the results so that scores ranged from 0-100. Note that for scores measuring function, a higher score represented a higher "better" level of functioning, while for scores measuring symptoms, a higher score represented a lower "worse" level of symptoms.

  8. BR23 Score Change Over Time: ITT Population [Up to 38 months.]

    The QLQ-BR23 incorporates 5 multi-item scales to assess systemic therapy side effects, arm symptoms, breast symptoms, body image and sexual functioning, and 3 single items assess sexual enjoyment, upset by hair loss and future perspective. Most items were scaled one to four except the items contributing to the global health status/QoL, which were seven-point questions. Raw scores were transformed using a linear transformation to standardize the results so that scores ranged from 0-100. Note that for scores measuring function, a higher score represented a higher "better" level of functioning, while for scores measuring symptoms, a higher score represented a lower "worse" level of symptoms.

  9. Population Mean ± Standard Deviation (SD) Area Under the Concentration-Time Curve (AUC) for NKTR-102 and Metabolites After Multiple Administration of 145 mg/m^2 NKTR-102 [25] [Up to 38 months.]

    Plasma concentrations of NKTR-102 and its major metabolites irinotecan, SN38, SN38G, and APC were measured using validated analytical methods. The population pharmacokinetic (PK) model-derived mean AUC values were computed by integration from t = 0 (start of first dose) to 21 days after the last dose. Integration was implemented using a separate compartment defined as the amount of drug or metabolite in the central compartment divided by the model-estimated volume of distribution.

  10. Population Mean ± SD Maximum Plasma Concentration (Cmax) for NKTR-102 and Metabolites After Multiple Administration of 145 mg/m^2 NKTR-102 [26] [Up to 38 months.]

    Plasma concentrations of NKTR-102 and its major metabolites irinotecan, SN38, SN38G, and APC were measured using validated analytical methods. The population PK model-derived mean Cmax values were computed by integration from t = 0 (start of first dose) to 21 days after the last dose. Integration was implemented using a separate compartment defined as the amount of drug or metabolite in the central compartment divided by the model-estimated volume of distribution.

  11. Population Mean ± SD Elimination Half-life (t½) for NKTR-102 After Multiple Administration of 145 mg/m^2 NKTR-102 [27] [Up to 38 months.]

    Plasma concentrations of NKTR-102 and its major metabolites irinotecan, SN38, SN38G, and APC were measured using validated analytical methods. The population PK model-derived mean t½ values were computed by integration from t = 0 (start of first dose) to 21 days after the last dose. Integration was implemented using a separate compartment defined as the amount of drug or metabolite in the central compartment divided by the model-estimated volume of distribution. The t½ of all analytes was primarily driven by NKTR-102. Thus, the NKTR-102 t½ of 37 days also applies to all NKTR-102 metabolites.

  12. Objective Response Rate (ORR): Efficacy Evaluable Population [Up to 38 months.]

    ORR was defined as the proportion of subjects with a complete response (CR) or a partial response (PR), assessed by the investigator based on Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 The analyses were performed for subjects in the efficacy evaluable population who had measurable disease as determined by the investigator at baseline.

Eligibility Criteria

Criteria

Ages Eligible for Study:
18 Years and Older
Sexes Eligible for Study:
Female
Accepts Healthy Volunteers:
No
Inclusion Criteria (major highlights):

  • Patient is an adult female with histologically or cytologically confirmed carcinoma of the breast for whom single-agent cytotoxic chemotherapy is indicated

  • Patient can have either measurable or non-measurable disease by RECIST.

  • Patient has received prior therapy (administered in the neoadjuvant, adjuvant and/or metastatic setting) with an anthracycline, a taxane and capecitabine

  • Patient has minimum of 2 and a maximum of 5 prior cytotoxic chemotherapy regimens with the last dose administered within 6 months. A minimum of two chemotherapy regimens had to be for locally recurrent and/or metastatic disease. All therapy received prior to a diagnosis of metastatic disease (eg, neoadjuvant, adjuvant or repeated adjuvant therapy following a second resection) is counted as one regimen.

  • Patient has Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.

  • Adequate hematopoietic, liver and kidney functions.

Exclusion Criteria (major highlights):

  • Patient with chemotherapy within 21 days, radiotherapy within 14 days, biological therapy with 14 days, hormonal therapy within 7 days and investigational therapy within 21 days prior to randomization.

  • Patient with any major surgery within 28 days prior to randomization.

  • Patient with concurrent use of biologic agents for the treatment of cancer including antibodies or any investigational agent(s).

  • Patient with prior treatment for cancer with a camptothecin derivative.

  • Patient with chronic or acute GI disorders resulting in diarrhea of any severity grade; patients who are using chronic anti-diarrheal supportive care to control diarrhea in the 28 days prior to randomization.

  • Patient received pharmacotherapy for hepatitis B or C, tuberculosis or HIV.

  • Patient with known cirrhosis diagnosed with Child-PUGH Class A or higher liver disease.

  • Patient with prior malignancy (other than breast cancer) except for non-melanoma skin cancer and carcinoma in situ (of the cervix or bladder), unless diagnosed and definitively treated more than 5 years prior to randomization.

  • Patient requiring daily use of oxygen supplementation in the 28 days prior to randomization.

  • Patients with significant cardiovascular impairment.

Contacts and Locations

Locations

Site City State Country Postal Code
1 Arizona Oncology Associates, PC - NAHOA Flagstaff Arizona United States 86001
2 Providence Health System - Southern California d/b/a Roy and Patricia Disney Family Cancer Center Burbank California United States 91505
3 University of Southern California Los Angeles California United States 90033
4 PMK Medical Group, Inc., DBA Ventura County Hematology Oncology Specialists Oxnard California United States 93030
5 Wilshire Oncology Medical Group, Inc. Pasadena California United States 91105
6 Desert Hematology Oncology Medical Group Rancho Mirage California United States 92270
7 University of California San Francisco San Francisco California United States 94143
8 Stanford University School of Medicine Stanford California United States 94305
9 Kaiser Permanente Vallejo California United States 94589
10 Rocky Mountain Cancer Centers Denver Colorado United States 80220
11 Pre clinical Science Bldg LR3 Washington District of Columbia United States 20007
12 Medstar Washington District of Columbia United States 20010
13 Mayo Clinic in Florida Jacksonville Florida United States 32224
14 University of Miami School of Medicine Miami Florida United States 33136
15 Advanced Medical Specialties Miami Florida United States 33176
16 Florida Cancer Research Institute Plantation Florida United States 33324
17 Hematology Oncology Associates of the Treasure Coast Port Saint Lucie Florida United States 34592
18 Northeast Georgia Cancer Care Athens Georgia United States 30607
19 Peachtree Hematology Oncology Consultants Atlanta Georgia United States 30318
20 Emory University Atlanta Georgia United States 30322
21 Central Georgia Cancer Care Macon Georgia United States 31201
22 Northwest Georgia Oncology Centers, P.C. Marietta Georgia United States 30060
23 Summit Cancer Care, P.C. Savannah Georgia United States 31405
24 The University of Chicago Medicine Chicago Illinois United States 60637
25 Oncology Specialists Niles Illinois United States 60714
26 Illinois Cancer Care, P.C. Peoria Illinois United States 61547
27 IU Health Simon Cancer Center Indianapolis Indiana United States 46202
28 Hall-Perrine Cancer Center, 3rd Floor Cedar Rapids Iowa United States 52403
29 Kansas City Cancer Center Overland Park Kansas United States 66210
30 Louisville Oncology Clinical Research Program Louisville Kentucky United States 40207
31 Maryland Oncology Hematology, P.A. Columbia Maryland United States 21044
32 Minnesota Oncology Hematology, P.A. Minneapolis Minnesota United States 55404
33 University of Minnesota Minneapolis Minnesota United States 55455
34 Mayo Clinic Rochester Minnesota United States 55905
35 Coborn Cancer Center Saint Cloud Minnesota United States 56303
36 Missouri Cancer Associates Columbia Missouri United States 65201
37 Washington University in St. Louis Saint Louis Missouri United States 63110
38 Missouri Baptist Medical Center Saint Louis Missouri United States 63131
39 Frontier Cancer Center and Blood Institute Billings Montana United States 59102
40 Dartmouth-Hitchcock Medical Center Lebanon New Hampshire United States 03756
41 Hematology-Oncology Associates of Northern NJ, PA Morristown New Jersey United States 07962
42 The cancer Institute of New Jersey New Brunswick New Jersey United States 08901
43 Cooper University Hospital Voorhees New Jersey United States 08043
44 UNM Cancer Center Albuquerque New Mexico United States 87106
45 New York Oncology Hematology, P.C. Albany New York United States 12206
46 Monte fiore Bronx New York United States 10461
47 Sciode Medical Associates, PLLC, d.b.a. Eastchester Center for Cancer Care Bronx New York United States 10469
48 Beth Israel Medical Center New York New York United States 10003
49 Cornell University New York New York United States 10065
50 SUNY Upstate Medical University Syracuse New York United States 13210
51 Carolinas Hematology Oncology Associates Charlotte North Carolina United States 28202
52 DUMC, Duke South Durham North Carolina United States 27710
53 Sanford Research/USD Fargo North Dakota United States 58122
54 University of Cincinnati Cincinnati Ohio United States 45267-0502
55 Comprehensive Breast Cancer Columbus Ohio United States 43212
56 Signal Point Clinical Research Center Middletown Ohio United States 45042
57 Northwest Cancer Specialists, P.C. Portland Oregon United States 97225
58 Medical Oncology Associates of Wyoming Valley, PC Kingston Pennsylvania United States 18704
59 Cancer Centers of the Carolinas Easley South Carolina United States 29640
60 Sanford Research/USD Sioux Falls South Dakota United States 57104
61 The West Clinic Memphis Tennessee United States 38120
62 Sarah Cannon Research Institute (SCRI) Nashville Tennessee United States 37203
63 Sarah Cannon Research Institute Nashville Tennessee United States 37203
64 Texas Oncology-Abilene Abilene Texas United States 79606
65 Texas Oncology-Austin Midtown Austin Texas United States 78705
66 Texas Oncology-Beaumont, Mamie McFaddin Ward Cancer Center Beaumont Texas United States 77702
67 Texas Oncology-Bedford Bedford Texas United States 76022
68 Texas Oncology-Medical City Dallas Dallas Texas United States 75230
69 Texas Oncology-Dallas Presbyterian Hospital Dallas Texas United States 75231
70 Texas Oncology-Baylor Charles A. Sammons Cancer Center Dallas Texas United States 75246
71 Texas Oncology-Denton South Denton Texas United States 76210
72 Texas Oncology-Fort Worth Fort Worth Texas United States 76104
73 Texas Oncology-Memorial City Houston Texas United States 77024
74 Texas Oncology-Lewisville Lewisville Texas United States 75067
75 Texas Oncology-Mesquite Mesquite Texas United States 75150
76 Texas Oncology-Midland Allison Cancer Center Midland Texas United States 79701
77 Texas Oncology, P.A. - Plano Plano Texas United States 92270
78 Cancer Care Centers of South Texas San Antonio Texas United States 78217
79 Texas Oncology - Sherman Sherman Texas United States 75090
80 Texas Oncology-Tyler Tyler Texas United States 75702
81 University of Virginia Charlottesville Virginia United States 22908
82 Virginia Oncology Associates Norfolk Virginia United States 23502
83 Oncology and Hematology Associates of Southwest Virginia, Inc., DBA Blue Ridge Cancer Care Salem Virginia United States 24153
84 Virginia Mason Medical Center Seattle Washington United States 98101
85 Seattle Cancer Care Alliance Seattle Washington United States 98109
86 Cancer Care Northwest Spokane Washington United States 99202
87 Yakima Valley Memorial Hospital/North Star Lodge Yakima Washington United States 98902
88 Cancer TEAM Bellin Health Green Bay Wisconsin United States 54313
89 Institut Jules Bordet Bruxelles Belgium 2-2-541-72-26
90 GHdC - Site Notre Dame Charleroi Belgium 6000
91 Universtair Ziekenhuis Antwerpen Edegem Belgium 2650
92 UZ Gent Medische Oncologie Gent Belgium 9000
93 UZ Leuven, Campus Gasthuisberg, trialbureau Algemene Medische Oncologie Leuven Belgium 3000
94 Centre Hospitalier Universitaire de Liège- Site du Sart Tilman Liège Belgium 4000
95 Centre Hospitalier Universitaire Ambroise Paré Mons, Belgium 7000
96 GZA Ziekenhuizen, Campus St Augustinus, CLINICAL TRIALS ONCOLOGY Wilrijk Belgium 2610
97 British Columbia Cancer Agency Vancouver British Columbia Canada V5Z 4E6
98 Odette Cancer Centre OCC Clinical Research Toronto Ontario Canada M4N 3M5
99 Princess Margaret Hospital Toronto Ontario Canada M5G 2M9
100 CHUM-Hopital Notre-Dame Montreal Quebec Canada H2L 4M1
101 MUHC- Montreal General Hospital Montreal Quebec Canada H3G1A4
102 Hôpital Charles-LeMoyne - CICM Québec Canada J4V 2H1
103 Institut Bergonie Service Oncologie Médicale Bordeaux France 33076
104 Sorecoh Le Mans France 72000
105 Centre Oscar Lambret Lille Cedex France 59020
106 Institut Paoli Calmettes, Service Pharmacie Marseille France 13273
107 Centra Regional de Lutte contre le Cancer Montpellier France 34298
108 Institut Curie, UGEC Paris France 75005
109 Hopital Tenon Service oncologie médicale Paris France 75020
110 Centre Régional de Lutte Contre le Cancer Nantes Atlantique René Gauducheau Saint Herblain France 44805
111 Institut de Cancérologie Gustave Roussy Villejuif France 94805
112 Klinikum St. Marien Amberg Amberg Germany
113 Onkoplus Berlin Germany 14195
114 Oncoresearch Dortmund Germany
115 Universitaetsklinikum Erlangen Erlangen Germany 91054
116 Wilhelm-Anton-Hospital gGmbH Goch Germany 47574
117 Universitaetsklinikum Heidelberg Heidelberg Germany 69120
118 Universitaetsklinikum Ulm, Frauenklinik Ulm Germany 89075
119 Istituto tumori Giovanni Paolo II-ospedale oncologico, Oncologia Medica e Sperimentale Bari Italy 700124
120 Via Olgettina Milano Italy 20132
121 Azienda Ospedaliero Universitaria Pisana, U.O. Oncologia Medica Pisa Italy 56126
122 Oncologia Ospedale Infermi- Viale Rimini Italy 47923
123 Istituto Nazionale tumori Regina Elena IRCCS Roma Italy 144
124 Chungbuk National University Hospital Cheongju-si Chungcheongbuk-do Korea, Republic of 361-711
125 Samsung Medical Center Irwon-dong Seoul Korea, Republic of 135-710
126 Hematology-oncology Department, Ajou University Hospital Sŏwŏn Suwon Korea, Republic of 443-721
127 Seoul National University Bundang Hospital Gyeonggi-do Korea, Republic of 463-707
128 Hematology-oncology Department, Ewha Womans University Mokdong Hospital Seoul Korea, Republic of 120-750
129 Severance Hospital, Yonsei University Health System Seoul Korea, Republic of 120-752
130 Asan Medical Center Seoul Korea, Republic of 138-736
131 Seoul National University Hospital, Soeul Korea, Republic of 110-744
132 VUmc Amsterdam Netherlands 1081
133 MUMC Maastricht Netherlands 6229
134 Tweesteden Ziekenhuis Tilburg Netherlands
135 Leningrad Regional Oncology Dispensary Kuz'molovskiy Russian Federation 188663
136 State Institution "Russian Oncology Research Centre named after N.N. Blokhin RAMS" Moscow Russian Federation 115478
137 Scientific Research Oncology Institute named after N.N. Petrov Saint Petersburg Russian Federation 197758
138 Non-state Health Institution "Dorozhnaya Clinical Hospital of OAO "Russian Railways" St. Petersburg Russian Federation 195271
139 St. Petersburg State Budget Healthcare Institution "City Clinical Oncology Dispensary" St. Petersburg Russian Federation 197022
140 Hospital Vall d'Hebron Barcelona Spain 08035
141 ICO l´Hospitalet - Hospital Duran i Reynals Barcelona Spain 08908
142 Hospital Universitari Arnau de Vilanova Lleida Spain 25198
143 Hospital General Universitario Gregorio Marañon Madrid Spain 28007
144 MD Anderson Cancer Center Arturo Madrid Spain 28033
145 Hospital Universitario Ramón y Cajal Madrid Spain 28034
146 Hospital Sant Joan de Reus Tarragona Spain 43204
147 Clinical Trials Unit, Velindre Cancer Centre Cardiff United Kingdom CF14 2TL
148 Beaston Oncology Center Glasgow United Kingdom G12 ONY
149 St James University Hospital Leeds United Kingdom LS97TF
150 NCRN London United Kingdom EC1A 7BE
151 The Christie Hospitals NHS Foundation Trust Manchester United Kingdom M20 4BX
152 Nottingham City Hospital Nottingham United Kingdom NG5 1PB
153 Cancer Clinical Trials Centre, Weston Park Hospital Sheffield United Kingdom S10 2SJ

Sponsors and Collaborators

  • Nektar Therapeutics

Investigators

  • Study Director: Alison Hannah, MD, Nektar Therapeutics

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.
Responsible Party:
Nektar Therapeutics
ClinicalTrials.gov Identifier:
NCT01492101
Other Study ID Numbers:
  • 11-PIR-11
First Posted:
Dec 14, 2011
Last Update Posted:
Jun 1, 2021
Last Verified:
May 1, 2021
Additional relevant MeSH terms:
Breast Neoplasms
Etirinotecan pegol

Study Results

Participant Flow

Recruitment Details
Pre-assignment Detail
Arm/Group Title NKTR-102 Physician's Treatment of Choice
Arm/Group Description NKTR-102: 145 mg/m2 NKTR-102 will be delivered q21day as a 90 minute intravenous (IV) infusion on day 1 of each treatment cycle. Treatment of Physician's Choice (TPC): One of the following Treatment of Physician Choice will be administered per standard of care: eribulin ixabepilone vinorelbine gemcitabine paclitaxel docetaxel or nab-paclitaxel
Period Title: Overall Study
STARTED 429 423
COMPLETED 92 81
NOT COMPLETED 337 342

Baseline Characteristics

Arm/Group Title NKTR-102 Physician's Treatment of Choice Total
Arm/Group Description NKTR-102: 145 mg/m2 NKTR-102 will be delivered q21day as a 90 minute intravenous (IV) infusion on day 1 of each treatment cycle. Treatment of Physician's Choice (TPC): One of the following Treatment of Physician Choice will be administered per standard of care: eribulin ixabepilone vinorelbine gemcitabine paclitaxel docetaxel or nab-paclitaxel Total of all reporting groups
Overall Participants 429 423 852
Age (Count of Participants)
<=18 years
0
0%
0
0%
0
0%
Between 18 and 65 years
341
79.5%
342
80.9%
683
80.2%
>=65 years
88
20.5%
81
19.1%
169
19.8%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]
55.1
(10.29)
55.2
(10.1)
55.2
(10.19)
Sex: Female, Male (Count of Participants)
Female
429
100%
423
100%
852
100%
Male
0
0%
0
0%
0
0%
Region of Enrollment (participants) [Number]
Canada
9
2.1%
15
3.5%
24
2.8%
South Korea
43
10%
42
9.9%
85
10%
Netherlands
1
0.2%
1
0.2%
2
0.2%
Belgium
53
12.4%
39
9.2%
92
10.8%
United States
198
46.2%
180
42.6%
378
44.4%
Italy
10
2.3%
12
2.8%
22
2.6%
United Kingdom
19
4.4%
23
5.4%
42
4.9%
France
36
8.4%
47
11.1%
83
9.7%
Germany
0
0%
4
0.9%
4
0.5%
Spain
46
10.7%
51
12.1%
97
11.4%
Russia
14
3.3%
9
2.1%
23
2.7%

Outcome Measures

1. Primary Outcome
Title Kaplan-Meier Estimate of Overall Survival: Intention to Treat (ITT) Population
Description Duration of OS was defined as the time from the date of randomisation to the date of death due to any cause. Subjects were followed until their date of death, loss to follow-up, withdrawal of consent for further follow-up for survival, or final database closure. OS was determined using the ITT population which included all subjects randomized into 1 of the 2 treatment arms. Subjects who were lost-to-follow-up or were not known to have died were censored at last date they were shown to be alive. Subjects who did not have any follow-up since the date of randomization were censored at the date of randomization.
Time Frame 36 Months

Outcome Measure Data

Analysis Population Description
[Not Specified]
Arm/Group Title NKTR-102 Physician's Treatment of Choice
Arm/Group Description NKTR-102: 145 mg/m2 NKTR-102 will be delivered q21day as a 90 minute intravenous (IV) infusion on day 1 of each treatment cycle. Treatment of Physician's Choice (TPC): One of the following Treatment of Physician Choice will be administered per standard of care: eribulin ixabepilone vinorelbine gemcitabine paclitaxel docetaxel or nab-paclitaxel
Measure Participants 429 423
Median (95% Confidence Interval) [Months]
12.4
10.3
Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection NKTR-102, Physician's Treatment of Choice
Comments
Type of Statistical Test Other
Comments Two-sided log-rank test, stratified by geographic region, prior use of eribulin, and receptor status.
Statistical Test of Hypothesis p-Value = 0.0835
Comments
Method Log Rank
Comments
Method of Estimation Estimation Parameter Hazard Ratio, log
Estimated Value 0.872
Confidence Interval (2-Sided) 95%
0.747 to 1.019
Parameter Dispersion Type:
Value:
Estimation Comments
2. Secondary Outcome
Title Kaplan-Meier Estimate of Progression-Free Survival (PFS): ITT Population
Description PFS was defined as the time from the date of randomization to the earliest date of disease progression (assessed by the investigator according to RECIST version 1.1) or death due to any cause. PFS was determined using the ITT population which included all subjects randomized into 1 of the 2 treatment arms. For subjects whose disease did not progress or who did not die, the PFS time was censored at the time of the last tumor assessment that demonstrated lack of disease progression. For subjects who received new anti-cancer therapy, the PFS time was censored at the start of the new anti-cancer therapy.
Time Frame Up to 38 months.

Outcome Measure Data

Analysis Population Description
[Not Specified]
Arm/Group Title NKTR-102 Physician's Treatment of Choice
Arm/Group Description NKTR-102: 145 mg/m2 NKTR-102 will be delivered q21day as a 90 minute intravenous (IV) infusion on day 1 of each treatment cycle. Treatment of Physician's Choice (TPC): One of the following Treatment of Physician Choice will be administered per standard of care: eribulin ixabepilone vinorelbine gemcitabine paclitaxel docetaxel or nab-paclitaxel
Measure Participants 429 423
Median (95% Confidence Interval) [Months]
2.4
2.8
Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection NKTR-102, Physician's Treatment of Choice
Comments
Type of Statistical Test Superiority
Comments
Statistical Test of Hypothesis p-Value = 0.3017
Comments
Method Log Rank
Comments
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.926
Confidence Interval (2-Sided) 95%
0.798 to 1.075
Parameter Dispersion Type:
Value:
Estimation Comments
3. Secondary Outcome
Title Clinical Benefit Rate (CBR): ITT Population
Description CBR was defined as the proportion of subjects with a CR, PR, or stable disease (SD) for at least 6 months (≥ 182 days).
Time Frame Up to 38 months.

Outcome Measure Data

Analysis Population Description
[Not Specified]
Arm/Group Title NKTR-102 Physician's Treatment of Choice
Arm/Group Description NKTR-102: 145 mg/m2 NKTR-102 will be delivered q21day as a 90 minute intravenous (IV) infusion on day 1 of each treatment cycle. Treatment of Physician's Choice (TPC): One of the following Treatment of Physician Choice will be administered per standard of care: eribulin ixabepilone vinorelbine gemcitabine paclitaxel docetaxel or nab-paclitaxel
Measure Participants 429 423
Number (95% Confidence Interval) [percentage of subjects]
20.5
19.6
4. Secondary Outcome
Title Duration of Response (DOR): Efficacy Evaluable Population
Description DOR was defined as the time from first documented CR or PR until the earliest evidence of disease progression or death from any cause. Subjects who were alive without documented disease progression per RECIST version 1.1 were censored at the date of last tumor assessment without disease progression or start of new anti-cancer therapy for the study disease.
Time Frame Up to 38 months.

Outcome Measure Data

Analysis Population Description
The population analyzed for this outcome measure solely comprised of patients who achieved CR or PR per RECIST.
Arm/Group Title NKTR-102 Physician's Treatment of Choice
Arm/Group Description NKTR-102: 145 mg/m2 NKTR-102 will be delivered q21day as a 90 minute intravenous (IV) infusion on day 1 of each treatment cycle. Treatment of Physician's Choice (TPC): One of the following Treatment of Physician Choice will be administered per standard of care: eribulin ixabepilone vinorelbine gemcitabine paclitaxel docetaxel or nab-paclitaxel
Measure Participants 58 61
Median (95% Confidence Interval) [Months]
3.9
3.7
5. Secondary Outcome
Title Incidence of Dose Reductions: Safety Population
Description Proportion of subjects who had a reduction in dose.
Time Frame Up to 38 months.

Outcome Measure Data

Analysis Population Description
[Not Specified]
Arm/Group Title NKTR-102 Physician's Treatment of Choice
Arm/Group Description NKTR-102: 145 mg/m2 NKTR-102 will be delivered q21day as a 90 minute intravenous (IV) infusion on day 1 of each treatment cycle. Treatment of Physician's Choice (TPC): One of the following Treatment of Physician Choice will be administered per standard of care: eribulin ixabepilone vinorelbine gemcitabine paclitaxel docetaxel or nab-paclitaxel
Measure Participants 425 406
Number [percentage of subjects]
27.5
28.3
6. Secondary Outcome
Title Quality of Life Questionnaire-Core 30 (QLQ-C30) Individual Scale, Overall Score: ITT Population
Description The QLQ-C30 is composed of 5 multi-item functional scales (physical, role, social, emotional and cognitive functioning), a global health status/QoL scale, 3 symptom scales (fatigue, nausea/vomiting, and pain), and 6 single items (financial impact, appetite loss, diarrhoea, constipation, insomnia and dyspnoea). Most items are scaled 1 to 4 (1 = not at all, 2 = a little, 3 = quite a bit, 4 = very much) except the items contributing to the global health status/QoL, which are 7-point questions (1 = very poor to 7 = excellent). Raw scores were transformed using a linear transformation to standardize the results so that scores range from 0 to 100. n=number of subjects who completed each individual scale. Note that for scores measuring function, a higher score represented a higher "better" level of functioning, while for scores measuring symptoms, a higher score represented a lower "worse" level of symptoms.
Time Frame Up to 39 months

Outcome Measure Data

Analysis Population Description
429 (ITT Population) 423 (ITT Population)
Arm/Group Title NKTR-102 Physician's Treatment of Choice
Arm/Group Description NKTR-102: 145 mg/m2 NKTR-102 will be delivered q21day as a 90 minute intravenous (IV) infusion on day 1 of each treatment cycle. Treatment of Physician's Choice (TPC): One of the following Treatment of Physician Choice will be administered per standard of care: eribulin ixabepilone vinorelbine gemcitabine paclitaxel docetaxel or nab-paclitaxel
Measure Participants 429 423
Global health status/QoL
61.4
(21.76)
58.0
(20.43)
Physical functioning
74.5
(19.72)
72.3
(19.74)
Role functioning
71.8
(26.81)
67.3
(26.93)
Emotional functioning
72.4
(21.86)
71.9
(20.06)
Cognitive functioning
82.5
(18.7)
81.2
(19.04)
Social functioning
73.0
(26.69)
71.0
(25.06)
Fatigue
37.7
(23.68)
41.3
(22.98)
Nausea and vomiting
8.6
(13.39)
9.9
(16.17)
Pain
32.3
(27.2)
35.3
(28.01)
Dyspnoea
24.5
(27.44)
23.6
(26.2)
Insomnia
29.3
(28.94)
31.5
(27.11)
Appetite loss
24.3
(27.55)
26.6
(27.89)
Constipation
18.0
(25.9)
21.0
(28.15)
Diarrhoea
6.3
(13.64)
5.6
(11.14)
Financial difficulties
26.4
(31.29)
21.9
(28.95)
7. Secondary Outcome
Title QLQ-C30 Individual Scale, Change Over Time: ITT Population
Description The QLQ-C30 is composed of 5 multi-item functional scales (physical, role, social, emotional and cognitive functioning), a global health status/QoL scale, 3 symptom scales (fatigue, nausea/vomiting, and pain), and 6 single items (financial impact, appetite loss, diarrhea, constipation, insomnia and dyspnea). Most items are scaled 1 to 4 (1 = not at all, 2 = a little, 3 = quite a bit, 4 = very much) except the items contributing to the global health status/QoL, which are 7-point questions (from 1 = very poor to 7 = excellent). Raw scores were transformed using a linear transformation to standardize the results so that scores range from 0 to 100. n=number of subjects who completed each individual scale. Note that for scores measuring function, a higher score represented a higher "better" level of functioning, while for scores measuring symptoms, a higher score represented a lower "worse" level of symptoms.
Time Frame From Baseline to Week 8, Week 16, Week 24, Week 32, Week 40, Week 48, Week 56.

Outcome Measure Data

Analysis Population Description
429 (ITT Population) 423 (ITT Population)
Arm/Group Title NKTR-102 Physician's Treatment of Choice
Arm/Group Description NKTR-102: 145 mg/m2 NKTR-102 will be delivered q21day as a 90 minute intravenous (IV) infusion on day 1 of each treatment cycle. Treatment of Physician's Choice (TPC): One of the following Treatment of Physician Choice will be administered per standard of care: eribulin ixabepilone vinorelbine gemcitabine paclitaxel docetaxel or nab-paclitaxel
Measure Participants 429 423
Global health status/QoL: Week 8
-4.4
(22.57)
-4.7
(20.37)
Global health status/QoL: Week 16
-2.5
(22.9)
-5.6
(21.86)
Global health status/QoL: Week 24
-1.8
(24.99)
-6.6
(22.47)
Global health status/QoL: Week 32
-0.2
(20.39)
-6.3
(26.66)
Global health status/QoL: Week 40
-5.2
(22.27)
-2.6
(19.41)
Global health status/QoL: Week 48
-2.3
(18.62)
-1.8
(20.71)
Global health status/QoL: Week 56
2.9
(17.79)
-11.1
(29.36)
Physical functioning: Week 8
-4.9
(17.98)
-7.1
(17.4)
Physical functioning: Week 16
-3.0
(20.63)
-7.0
(18.26)
Physical functioning: Week 24
0.3
(20.93)
-4.7
(15.9)
Physical functioning: Week 32
-3.0
(18.88)
-8.5
(20.4)
Physical functioning: Week 40
-1.9
(19.23)
-6.4
(18.81)
Physical functioning: Week 48
0.2
(17.66)
-7.4
(16.46)
Physical functioning: Week 56
2.2
(13.48)
-10.4
(24.27)
Role functioning: Week 8
-6.6
(27.26)
-8.3
(27.37)
Role functioning: Week 16
-4.8
(26.06)
-8.3
(24.41)
Role functioning: Week 24
-7.8
(33.3)
-10.8
(26.72)
Role functioning: Week 32
-9.7
(19.03)
-12.2
(29.81)
Role functioning: Week 40
-8.7
(30.94)
-7.8
(27.93)
Role functioning: Week 48
-3.1
(25.38)
-5.7
(21.7)
Role functioning: Week 56
-2.6
(17.12)
-9.4
(35.08)
Emotional functioning: Week 8
-0.5
(19.65)
-2.0
(19.95)
Emotional functioning: Week 16
2.7
(18.93)
-1.6
(20.57)
Emotional functioning: Week 24
-0.6
(22.34)
-3.7
(18.95)
Emotional functioning: Week 32
-2.8
(21.02)
-7.6
(20.88)
Emotional functioning: Week 40
-1.4
(26.12)
0.8
(19.11)
Emotional functioning: Week 48
0.9
(21.37)
1.2
(18.83)
Emotional functioning: Week 56
-3.6
(19.72)
-4.7
(25.29)
Cognitive functioning: Week 8
-3.3
(18.46)
-3.2
(19.44)
Cognitive functioning: Week 16
-1.4
(17.67)
-4.4
(20.81)
Cognitive functioning: Week 24
-1.8
(17.26)
-2.2
(17.12)
Cognitive functioning: Week 32
-4.6
(17.82)
-7.9
(20.14)
Cognitive functioning: Week 40
-5.7
(18.61)
-3.5
(21.6)
Cognitive functioning: Week 48
-4.6
(18.04)
2.2
(17.75)
Cognitive functioning: Week 56
-2.9
(18.25)
-6.7
(22.97)
Social functioning: Week 8
-4.9
(27.46)
-6.2
(24.04)
Social functioning: Week 16
0.4
(27.57)
-6.4
(24.2)
Social functioning: Week 24
-3.4
(25.68)
-7.2
(24.1)
Social functioning: Week 32
-8.8
(20.61)
-7.2
(30.1)
Social functioning: Week 40
-9.7
(26.09)
-7.0
(20.98)
Social functioning: Week 48
-5.5
(17.86)
-6.6
(20.71)
Social functioning: Week 56
-3.2
(22.25)
-24.4
(29.96)
Fatigue: Week 8
6.7
(22.88)
6.6
(22.17)
Fatigue: Week 16
3.7
(22.63)
7.7
(22.84)
Fatigue: Week 24
3.0
(26.51)
3.6
(21.23)
Fatigue: Week 32
5.0
(21.84)
6.6
(24.25)
Fatigue: Week 40
4.1
(26.65)
2.3
(19.02)
Fatigue: Week 48
0.9
(18.69)
6.7
(14.53)
Fatigue: Week 56
2.1
(19.57)
4.5
(24.36)
Nausea and vomiting: Week 8
12.8
(23.28)
4.2
(21.94)
Nausea and vomiting: Week 16
8.8
(19.85)
-2.0
(19.1)
Nausea and vomiting: Week 24
7.2
(22.57)
-0.1
(16.55)
Nausea and vomiting: Week 32
6.5
(14.21)
3.5
(18.81)
Nausea and vomiting: Week 40
4.5
(12.97)
5.6
(23.61)
Nausea and vomiting: Week 48
5.0
(13.77)
3.9
(28.92)
Nausea and vomiting: Week 56
8.0
(11.66)
1.6
(23.02)
Pain: Week 8
-1.7
(26.08)
2.4
(27.03)
Pain: Week 16
-5.0
(26.9)
1.9
(27.8)
Pain: Week 24
-4.1
(29.35)
2.1
(27.78)
Pain: Week 32
-1.0
(27.17)
3.9
(32.49)
Pain: Week 40
1.6
(31.82)
1.3
(29.96)
Pain: Week 48
-0.8
(30.82)
-0.4
(25.23)
Pain: Week 56
-4.2
(22.88)
0.5
(33.95)
Dyspnoea: Week 8
0.7
(25.02)
5.8
(24.59)
Dyspnoea: Week 16
-1.1
(26.34)
4.6
(26.99)
Dyspnoea: Week 24
-2.0
(25.65)
1.4
(20.47)
Dyspnoea: Week 32
0
(24.77)
8.6
(29.67)
Dyspnoea: Week 40
2.4
(27.93)
5.0
(25.95)
Dyspnoea: Week 48
-5.6
(26.38)
-0.9
(19.62)
Dyspnoea: Week 56
-7.1
(18.36)
-1.2
(22.13)
Insomnia: Week 8
-1.5
(28.1)
3.3
(30.28)
Insomnia: Week 16
-1.4
(24.4)
2.1
(27.2)
Insomnia: Week 24
-2.7
(31.77)
1.3
(26.41)
Insomnia: Week 32
1.5
(34.04)
2.5
(30.14)
Insomnia: Week 40
0
(31.51)
4.4
(22.71)
Insomnia: Week 48
2.8
(28.05)
0.9
(34.01)
Insomnia: Week 56
-1.3
(35.57)
-1.0
(27.53)
Appetite loss: Week 8
11.6
(32.03)
4.0
(30.26)
Appetite loss: Week 16
9.4
(32.16)
-2.1
(29.75)
Appetite loss: Week 24
4.6
(36.55)
-1.6
(30.57)
Appetite loss: Week 32
8.9
(35.42)
0
(32.04)
Appetite loss: Week 40
6.9
(38.57)
5.4
(38.58)
Appetite loss: Week 48
2.2
(34.67)
13.0
(45.93)
Appetite loss: Week 56
14.7
(35.38)
1.0
(39.19)
Constipation: Week 8
2.1
(29.95)
6.7
(27.81)
Constipation: Week 16
0.2
(31.03)
3.1
(30.96)
Constipation: Week 24
0.5
(29.65)
-2.0
(28.14)
Constipation: Week 32
4.6
(29.83)
0.3
(26.53)
Constipation: Week 40
1.0
(28.44)
-3.2
(29.32)
Constipation: Week 48
-0.6
(31.65)
7.0
(33.48)
Constipation: Week 56
1.9
(34.42)
-4.4
(35.34)
Diarrhoea: Week 8
10.2
(27.98)
1.8
(16.87)
Diarrhoea: Week 16
10.8
(26.97)
3.4
(19.07)
Diarrhoea: Week 24
9.4
(26.43)
2.4
(16.39)
Diarrhoea: Week 32
9.2
(21.3)
0.8
(17.07)
Diarrhoea: Week 40
8.3
(23.06)
7.8
(27.93)
Diarrhoea: Week 48
12.1
(22.23)
0
(17.57)
Diarrhoea: Week 56
4.5
(14.57)
6.7
(31.37)
Financial difficulties: Week 8
-0.7
(22.87)
0.6
(22.42)
Financial difficulties: Week 16
0.8
(23.26)
1.0
(22.48)
Financial difficulties: Week 24
1.0
(21.09)
4.6
(28.38)
Financial difficulties: Week 32
1.2
(20.28)
10.2
(26.81)
Financial difficulties: Week 40
4.2
(21.61)
-1.7
(19.74)
Financial difficulties: Week 48
0
(22.27)
3.5
(18.9)
Financial difficulties: Week 56
-1.9
(21.25)
5.6
(25.72)
Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection NKTR-102, Physician's Treatment of Choice
Comments Global health status/QoL: change from baseline to last assessment (Week 56)
Type of Statistical Test Equivalence
Comments [2] - Analysis of variance with change from baseline in linear transformed score at the last visit as the dependent variable and treatment arm, geographic region, prior use of eribulin, and receptor status as fixed effects.
Statistical Test of Hypothesis p-Value 0.635
Comments
Method F-test
Comments
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.8
Confidence Interval (2-Sided) 95%
-2.65 to 4.33
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection NKTR-102, Physician's Treatment of Choice
Comments
Type of Statistical Test Equivalence
Comments [3] - Analysis of variance with change from baseline in linear transformed score at the last visit as the dependent variable and treatment arm, geographic region, prior use of eribulin, and receptor status as fixed effects.
Statistical Test of Hypothesis p-Value 0.1656
Comments
Method F-test
Comments
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 2.1
Confidence Interval (2-Sided) 95%
-0.88 to 5.14
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection NKTR-102, Physician's Treatment of Choice
Comments
Type of Statistical Test Equivalence
Comments [4] - Analysis of variance with change from baseline in linear transformed score at the last visit as the dependent variable and treatment arm, geographic region, prior use of eribulin, and receptor status as fixed effects.
Statistical Test of Hypothesis p-Value 0.8356
Comments
Method F-test
Comments
Method of Estimation Estimation Parameter Median Difference (Final Values)
Estimated Value 0.5
Confidence Interval (2-Sided) 95%
-3.9 to 4.82
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection NKTR-102, Physician's Treatment of Choice
Comments
Type of Statistical Test Equivalence
Comments [5] - Analysis of variance with change from baseline in linear transformed score at the last visit as the dependent variable and treatment arm, geographic region, prior use of eribulin, and receptor status as fixed effects.
Statistical Test of Hypothesis p-Value 0.7727
Comments
Method F-test
Comments
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.5
Confidence Interval (2-Sided) 95%
-2.88 to 3.88
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection NKTR-102, Physician's Treatment of Choice
Comments
Type of Statistical Test Equivalence
Comments [6] - Analysis of variance with change from baseline in linear transformed score at the last visit as the dependent variable and treatment arm, geographic region, prior use of eribulin, and receptor status as fixed effects.
Statistical Test of Hypothesis p-Value 0.7446
Comments
Method F-test
Comments
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.5
Confidence Interval (2-Sided) 95%
-2.56 to 3.59
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection NKTR-102, Physician's Treatment of Choice
Comments
Type of Statistical Test Equivalence
Comments [7] - Analysis of variance with change from baseline in linear transformed score at the last visit as the dependent variable and treatment arm, geographic region, prior use of eribulin, and receptor status as fixed effects.
Statistical Test of Hypothesis p-Value 0.9169
Comments
Method F-test
Comments
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.2
Confidence Interval (2-Sided) 95%
-4.0 to 4.45
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 7
Statistical Analysis Overview Comparison Group Selection NKTR-102, Physician's Treatment of Choice
Comments
Type of Statistical Test Equivalence
Comments [8] - Analysis of variance with change from baseline in linear transformed score at the last visit as the dependent variable and treatment arm, geographic region, prior use of eribulin, and receptor status as fixed effects.
Statistical Test of Hypothesis p-Value 0.9731
Comments
Method F-test
Comments
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.1
Confidence Interval (2-Sided) 95%
-3.66 to 3.79
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 8
Statistical Analysis Overview Comparison Group Selection NKTR-102, Physician's Treatment of Choice
Comments
Type of Statistical Test Equivalence
Comments [9] - Analysis of variance with change from baseline in linear transformed score at the last visit as the dependent variable and treatment arm, geographic region, prior use of eribulin, and receptor status as fixed effects.
Statistical Test of Hypothesis p-Value <0.0001
Comments
Method F-test
Comments
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 7.3
Confidence Interval (2-Sided) 95%
3.88 to 10.67
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 9
Statistical Analysis Overview Comparison Group Selection NKTR-102, Physician's Treatment of Choice
Comments
Type of Statistical Test Equivalence
Comments [10] - Analysis of variance with change from baseline in linear transformed score at the last visit as the dependent variable and treatment arm, geographic region, prior use of eribulin, and receptor status as fixed effects.
Statistical Test of Hypothesis p-Value 0.1252
Comments
Method F-test
Comments
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -2.8
Confidence Interval (2-Sided) 95%
-7.59 to 0.93
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 10
Statistical Analysis Overview Comparison Group Selection NKTR-102, Physician's Treatment of Choice
Comments
Type of Statistical Test Equivalence
Comments [11] - Analysis of variance with change from baseline in linear transformed score at the last visit as the dependent variable and treatment arm, geographic region, prior use of eribulin, and receptor status as fixed effects.
Statistical Test of Hypothesis p-Value 0.1717
Comments
Method F-test
Comments
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -2.8
Confidence Interval (2-Sided) 95%
-6.83 to 1.22
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 11
Statistical Analysis Overview Comparison Group Selection NKTR-102, Physician's Treatment of Choice
Comments
Type of Statistical Test Equivalence
Comments [12] - Analysis of variance with change from baseline in linear transformed score at the last visit as the dependent variable and treatment arm, geographic region, prior use of eribulin, and receptor status as fixed effects.
Statistical Test of Hypothesis p-Value 0.5513
Comments
Method F-test
Comments
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -1.4
Confidence Interval (2-Sided) 95%
-5.95 to 3.18
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 12
Statistical Analysis Overview Comparison Group Selection NKTR-102, Physician's Treatment of Choice
Comments
Type of Statistical Test Equivalence
Comments [13] - Analysis of variance with change from baseline in linear transformed score at the last visit as the dependent variable and treatment arm, geographic region, prior use of eribulin, and receptor status as fixed effects.
Statistical Test of Hypothesis p-Value 0.0009
Comments
Method F-test
Comments
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 8.6
Confidence Interval (2-Sided) 95%
3.57 to 13.72
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 13
Statistical Analysis Overview Comparison Group Selection NKTR-102, Physician's Treatment of Choice
Comments
Type of Statistical Test Equivalence
Comments [14] - Analysis of variance with change from baseline in linear transformed score at the last visit as the dependent variable and treatment arm, geographic region, prior use of eribulin, and receptor status as fixed effects.
Statistical Test of Hypothesis p-Value 0.2337
Comments
Method F-test
Comments
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -2.8
Confidence Interval (2-Sided) 95%
-7.35 to 1.8
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 14
Statistical Analysis Overview Comparison Group Selection NKTR-102, Physician's Treatment of Choice
Comments
Type of Statistical Test Equivalence
Comments [15] - Analysis of variance with change from baseline in linear transformed score at the last visit as the dependent variable and treatment arm, geographic region, prior use of eribulin, and receptor status as fixed effects.
Statistical Test of Hypothesis p-Value <0.0001
Comments
Method F-test
Comments
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 10.3
Confidence Interval (2-Sided) 95%
6.6 to 13.98
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 15
Statistical Analysis Overview Comparison Group Selection NKTR-102, Physician's Treatment of Choice
Comments
Type of Statistical Test Equivalence
Comments [16] - Analysis of variance with change from baseline in linear transformed score at the last visit as the dependent variable and treatment arm, geographic region, prior use of eribulin, and receptor status as fixed effects.
Statistical Test of Hypothesis p-Value 0.99
Comments
Method F-test
Comments
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0
Confidence Interval (2-Sided) 95%
-3.74 to 3.69
Parameter Dispersion Type:
Value:
Estimation Comments
8. Secondary Outcome
Title Quality of Life Questionnaire-breast Cancer-specific Module (BR23) Score Value: ITT Population
Description The QLQ-BR23 incorporates 5 multi-item scales to assess systemic therapy side effects, arm symptoms, breast symptoms, body image and sexual functioning, and 3 single items to assess sexual enjoyment, upset by hair loss and future perspective. Most items were scaled one to four except the items contributing to the global health status/QoL, which were seven-point questions. Raw scores were transformed using a linear transformation to standardize the results so that scores ranged from 0-100. Note that for scores measuring function, a higher score represented a higher "better" level of functioning, while for scores measuring symptoms, a higher score represented a lower "worse" level of symptoms.
Time Frame Baseline

Outcome Measure Data

Analysis Population Description
429 (ITT Population) 423 (ITT Population)
Arm/Group Title NKTR-102 Physician's Treatment of Choice
Arm/Group Description NKTR-102: 145 mg/m2 NKTR-102 will be delivered q21day as a 90 minute intravenous (IV) infusion on day 1 of each treatment cycle. Treatment of Physician's Choice (TPC): One of the following Treatment of Physician Choice will be administered per standard of care: eribulin ixabepilone vinorelbine gemcitabine paclitaxel docetaxel or nab-paclitaxel
Measure Participants 429 423
Body image
69.5
(28.94)
69.9
(27.91)
Sexual functioning
14.1
(19.24)
13.3
(18.91)
Sexual enjoyment
36.1
(29.25)
34.2
(30.77)
Future perspective
38.7
(30.53)
36.1
(29.0)
Systemic therapy side effects
21.9
(16.37)
22.3
(15.15)
Breast symptoms
15.3
(21.55)
15.8
(20.79)
Arm symptoms
20.8
(23.4)
22.2
(22.75)
Upset by hair loss
33.2
(34.15)
30.5
(33.29)
9. Secondary Outcome
Title BR23 Score Change Over Time: ITT Population
Description The QLQ-BR23 incorporates 5 multi-item scales to assess systemic therapy side effects, arm symptoms, breast symptoms, body image and sexual functioning, and 3 single items assess sexual enjoyment, upset by hair loss and future perspective. Most items were scaled one to four except the items contributing to the global health status/QoL, which were seven-point questions. Raw scores were transformed using a linear transformation to standardize the results so that scores ranged from 0-100. Note that for scores measuring function, a higher score represented a higher "better" level of functioning, while for scores measuring symptoms, a higher score represented a lower "worse" level of symptoms.
Time Frame Up to 38 months.

Outcome Measure Data

Analysis Population Description
429 (ITT Population) 423 (ITT Population)
Arm/Group Title NKTR-102 Physician's Treatment of Choice
Arm/Group Description NKTR-102: 145 mg/m2 NKTR-102 will be delivered q21day as a 90 minute intravenous (IV) infusion on day 1 of each treatment cycle. Treatment of Physician's Choice (TPC): One of the following Treatment of Physician Choice will be administered per standard of care: eribulin ixabepilone vinorelbine gemcitabine paclitaxel docetaxel or nab-paclitaxel
Measure Participants 429 423
Body image: Week 8
-0.8
(21.99)
-2.2
(20.49)
Body image: Week 16
-0.8
(24.31)
-2.3
(20.91)
Body image: Week 24
0.8
(23.58)
-4.7
(20.97)
Body image: Week 32
-1.2
(26.27)
-0.3
(22.23)
Body image: Week 40
3.3
(22.63)
-2.4
(20.98)
Body image: Week 48
-0.3
(25.47)
-1.1
(28.93)
Body image: Week 56
3.9
(25.53)
-10.2
(26.61)
Sexual functioning: Week 8
-0.8
(16.07)
-2.2
(16.26)
Sexual functioning: Week 16
0.1
(16.67)
-0.8
(17.28)
Sexual functioning: Week 24
-2.8
(16.72)
-1.4
(15.7)
Sexual functioning: Week 32
-2.2
(19.12)
-.7
(12.82)
Sexual functioning: Week 40
-5.4
(16.66)
2.7
(16.27)
Sexual functioning: Week 48
-9.6
(19.68)
1.6
(15.88)
Sexual functioning: Week 56
-5.3
(17.33)
1.7
(13.06)
Sexual enjoyment: Week 8
2.6
(19.84)
-4.2
(23.64)
Sexual enjoyment: Week 16
-0.3
(18.41)
-8.6
(21.7)
Sexual enjoyment: Week 24
1.9
(29.72)
-3.5
(28.1)
Sexual enjoyment: Week 32
2.0
(23.48)
-2.6
(20.24)
Sexual enjoyment: Week 40
-15.3
(29.69)
7.1
(13.11)
Sexual enjoyment: Week 48
-27.8
(25.09)
6.7
(14.91)
Sexual enjoyment: Week 56
-9.8
(16.27)
0
(0)
Future perspective: Week 8
3.5
(28.3)
1.5
(27.21)
Future perspective: Week 16
6.9
(27.17)
3.6
(29.18)
Future perspective: Week 24
9.3
(31.1)
6.6
(29.55)
Future perspective: Week 32
6.1
(30.19)
4.4
(35.86)
Future perspective: Week 40
7.1
(28.05)
13.3
(37.75)
Future perspective: Week 48
9.2
(27.31)
6.1
(35.66)
Future perspective: Week 56
16.0
(28.25)
-3.1
(45.22)
Systemic therapy side effects: Week 8
2.3
(13.74)
7.9
(16.03)
Systemic therapy side effects: Week 16
3.0
(14.95)
9.1
(17.7)
Systemic therapy side effects: Week 24
2.2
(15.55)
6.9
(17.39)
Systemic therapy side effects: Week 32
3.5
(13.5)
7.3
(18.01)
Systemic therapy side effects: Week 40
3.2
(16.62)
10.1
(18.33)
Systemic therapy side effects: Week 48
0.3
(11.74)
6.4
(15.68)
Systemic therapy side effects: Week 56
-1.1
(11.06)
6.8
(21.84)
Breast symptoms: Week 8
-1.7
(15.21)
-0.2
(13.82)
Breast symptoms: Week 16
-3.5
(14.6)
0.1
(14.64)
Breast symptoms: Week 24
-4.8
(10.52)
-1.1
(13.48)
Breast symptoms: Week 32
-2.5
(14.26)
-2.8
(13.63)
Breast symptoms: Week 40
-1.9
(14.59)
-0.2
(11.02)
Breast symptoms: Week 48
-2.7
(12.16)
0
(13.79)
Breast symptoms: Week 56
-3.4
(13.28)
2.5
(12.15)
Arm symptoms: Week 8
-3.0
(16.72)
-0.9
(15.01)
Arm symptoms: Week 16
-5.1
(17.24)
1.1
(18.24)
Arm symptoms: Week 24
-4.9
(20.06)
-0.3
(19.56)
Arm symptoms: Week 32
-4.4
(18.39)
-0.5
(19.03)
Arm symptoms: Week 40
-6.0
(21.86)
5.2
(18.39)
Arm symptoms: Week 48
-5.6
(20.89)
-1.4
(12.98)
Arm symptoms: Week 56
-5.6
(19.44)
-1.4
(12.98)
Upset by hair loss: Week 8
-4.7
(32.28)
0.1
(28.63)
Upset by hair loss: Week 16
8.3
(33.61)
2.9
(31.24)
Upset by hair loss: Week 24
6.8
(35.02)
3.5
(30.3)
Upset by hair loss: Week 32
6.9
(31.76)
-2.3
(29.68)
Upset by hair loss: Week 40
-4.2
(30.05)
20.2
(29.37)
Upset by hair loss: Week 48
-16.7
(31.91)
21.7
(36.89)
Upset by hair loss: Week 56
-14.6
(30.13)
16.7
(44.1)
Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection NKTR-102, Physician's Treatment of Choice
Comments
Type of Statistical Test Equivalence
Comments [17] - Analysis of variance with change from baseline in linear transformed score at the last visit as the dependent variable and treatment arm, geographic region, prior use of eribulin, and receptor status as fixed effects.
Statistical Test of Hypothesis p-Value 0.5833
Comments
Method F-test
Comments
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.9
Confidence Interval (2-Sided) 95%
-2.42 to 4.29
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection NKTR-102, Physician's Treatment of Choice
Comments
Type of Statistical Test Equivalence
Comments [18] - Analysis of variance with change from baseline in linear transformed score at the last visit as the dependent variable and treatment arm, geographic region, prior use of eribulin, and receptor status as fixed effects.
Statistical Test of Hypothesis p-Value 0.3098
Comments
Method F-test
Comments
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 1.3
Confidence Interval (2-Sided) 95%
-1.24 to 3.9
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection NKTR-102, Physician's Treatment of Choice
Comments
Type of Statistical Test Equivalence
Comments [19] - Analysis of variance with change from baseline in linear transformed score at the last visit as the dependent variable and treatment arm, geographic region, prior use of eribulin, and receptor status as fixed effects.
Statistical Test of Hypothesis p-Value 0.6264
Comments
Method F-test
Comments
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 1.1
Confidence Interval (2-Sided) 95%
-3.39 to 5.63
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection NKTR-102, Physician's Treatment of Choice
Comments
Type of Statistical Test Equivalence
Comments [20] - Analysis of variance with change from baseline in linear transformed score at the last visit as the dependent variable and treatment arm, geographic region, prior use of eribulin, and receptor status as fixed effects.
Statistical Test of Hypothesis p-Value 0.0003
Comments
Method F-test
Comments
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -4.6
Confidence Interval (2-Sided) 95%
-7.11 to -2.1
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection NKTR-102, Physician's Treatment of Choice
Comments
Type of Statistical Test Equivalence
Comments [21] - Analysis of variance with change from baseline in linear transformed score at the last visit as the dependent variable and treatment arm, geographic region, prior use of eribulin, and receptor status as fixed effects.
Statistical Test of Hypothesis p-Value 0.2473
Comments
Method F-test
Comments
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -1.4
Confidence Interval (2-Sided) 95%
-3.84 to 0.99
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection NKTR-102, Physician's Treatment of Choice
Comments
Type of Statistical Test Equivalence
Comments [22] - Analysis of variance with change from baseline in linear transformed score at the last visit as the dependent variable and treatment arm, geographic region, prior use of eribulin, and receptor status as fixed effects.
Statistical Test of Hypothesis p-Value 0.0333
Comments
Method F-test
Comments
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -2.9
Confidence Interval (2-Sided) 95%
-5.54 to -0.23
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 7
Statistical Analysis Overview Comparison Group Selection NKTR-102, Physician's Treatment of Choice
Comments
Type of Statistical Test Equivalence
Comments [23] - Analysis of variance with change from baseline in linear transformed score at the last visit as the dependent variable and treatment arm, geographic region, prior use of eribulin, and receptor status as fixed effects.
Statistical Test of Hypothesis p-Value 0.2575
Comments
Method F-test
Comments
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -4.5
Confidence Interval (2-Sided) 95%
-12.2 to 3.28
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 8
Statistical Analysis Overview Comparison Group Selection NKTR-102, Physician's Treatment of Choice
Comments
Type of Statistical Test Equivalence
Comments [24] - Analysis of variance with change from baseline in linear transformed score at the last visit as the dependent variable and treatment arm, geographic region, prior use of eribulin, and receptor status as fixed effects.
Statistical Test of Hypothesis p-Value 0.1072
Comments
Method F-test
Comments
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 5.6
Confidence Interval (2-Sided) 95%
-1.22 to 12.34
Parameter Dispersion Type:
Value:
Estimation Comments
10. Secondary Outcome
Title Population Mean ± Standard Deviation (SD) Area Under the Concentration-Time Curve (AUC) for NKTR-102 and Metabolites After Multiple Administration of 145 mg/m^2 NKTR-102 [25]
Description Plasma concentrations of NKTR-102 and its major metabolites irinotecan, SN38, SN38G, and APC were measured using validated analytical methods. The population pharmacokinetic (PK) model-derived mean AUC values were computed by integration from t = 0 (start of first dose) to 21 days after the last dose. Integration was implemented using a separate compartment defined as the amount of drug or metabolite in the central compartment divided by the model-estimated volume of distribution.
Time Frame Up to 38 months.

Outcome Measure Data

Analysis Population Description
[Not Specified]
Arm/Group Title NKTR-102
Arm/Group Description NKTR-102: 145 mg/m2 NKTR-102 will be delivered q21day as a 90 minute intravenous (IV) infusion on day 1 of each treatment cycle.
Measure Participants 95
NKTR-102
4619
(4874)
Irinotecan
18.8
(22.1)
SN38
5.32
(6.74)
SN38G
40.6
(39.2)
APC
4.0
(5.1)
11. Secondary Outcome
Title Population Mean ± SD Maximum Plasma Concentration (Cmax) for NKTR-102 and Metabolites After Multiple Administration of 145 mg/m^2 NKTR-102 [26]
Description Plasma concentrations of NKTR-102 and its major metabolites irinotecan, SN38, SN38G, and APC were measured using validated analytical methods. The population PK model-derived mean Cmax values were computed by integration from t = 0 (start of first dose) to 21 days after the last dose. Integration was implemented using a separate compartment defined as the amount of drug or metabolite in the central compartment divided by the model-estimated volume of distribution.
Time Frame Up to 38 months.

Outcome Measure Data

Analysis Population Description
[Not Specified]
Arm/Group Title NKTR-102
Arm/Group Description NKTR-102: 145 mg/m2 NKTR-102 will be delivered q21day as a 90 minute intravenous (IV) infusion on day 1 of each treatment cycle.
Measure Participants 95
NKTR-102
62701
(14576)
Irinotecan
138
(61.8)
SN38
4.45
(1.82)
SN38G
47.7
(43.1)
APC
7.3
(6.7)
12. Secondary Outcome
Title Population Mean ± SD Elimination Half-life (t½) for NKTR-102 After Multiple Administration of 145 mg/m^2 NKTR-102 [27]
Description Plasma concentrations of NKTR-102 and its major metabolites irinotecan, SN38, SN38G, and APC were measured using validated analytical methods. The population PK model-derived mean t½ values were computed by integration from t = 0 (start of first dose) to 21 days after the last dose. Integration was implemented using a separate compartment defined as the amount of drug or metabolite in the central compartment divided by the model-estimated volume of distribution. The t½ of all analytes was primarily driven by NKTR-102. Thus, the NKTR-102 t½ of 37 days also applies to all NKTR-102 metabolites.
Time Frame Up to 38 months.

Outcome Measure Data

Analysis Population Description
[Not Specified]
Arm/Group Title NKTR-102
Arm/Group Description NKTR-102: 145 mg/m2 NKTR-102 will be delivered q21day as a 90 minute intravenous (IV) infusion on day 1 of each treatment cycle.
Measure Participants 95
Mean (Standard Deviation) [days]
36.8
(1.4)
13. Secondary Outcome
Title Objective Response Rate (ORR): Efficacy Evaluable Population
Description ORR was defined as the proportion of subjects with a complete response (CR) or a partial response (PR), assessed by the investigator based on Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 The analyses were performed for subjects in the efficacy evaluable population who had measurable disease as determined by the investigator at baseline.
Time Frame Up to 38 months.

Outcome Measure Data

Analysis Population Description
[Not Specified]
Arm/Group Title NKTR-102 Physician's Treatment of Choice
Arm/Group Description NKTR-102: 145 mg/m2 NKTR-102 will be delivered q21day as a 90 minute intravenous (IV) infusion on day 1 of each treatment cycle. Treatment of Physician's Choice (TPC): One of the following Treatment of Physician Choice will be administered per standard of care: eribulin ixabepilone vinorelbine gemcitabine paclitaxel docetaxel or nab-paclitaxel
Measure Participants 354 358
Number (95% Confidence Interval) [percentage of subjects]
16.4
17.0

Adverse Events

Time Frame Up to 38 months.
Adverse Event Reporting Description Safety Population NKTR-102 = 425; TPC = 406
Arm/Group Title NKTR-102 Physician's Treatment of Choice
Arm/Group Description NKTR-102: 145 mg/m2 NKTR-102 will be delivered q21day as a 90 minute intravenous (IV) infusion on day 1 of each treatment cycle. Treatment of Physician's Choice (TPC): One of the following Treatment of Physician Choice will be administered per standard of care: eribulin ixabepilone vinorelbine gemcitabine paclitaxel docetaxel or nab-paclitaxel
All Cause Mortality
NKTR-102 Physician's Treatment of Choice
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total 323/425 (76%) 322/406 (79.3%)
Serious Adverse Events
NKTR-102 Physician's Treatment of Choice
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total 128/425 (30.1%) 129/406 (31.8%)
Blood and lymphatic system disorders
Febrile neutropenia 2/425 (0.5%) 6/406 (1.5%)
Anaemia 2/425 (0.5%) 0/406 (0%)
Pancytopenia 2/425 (0.5%) 0/406 (0%)
Coagulopathy 1/425 (0.2%) 0/406 (0%)
Idiopathic thrombocytopenic purpura 0/425 (0%) 1/406 (0.2%)
Microangiopathic haemolytic anaemia 1/425 (0.2%) 0/406 (0%)
Neutropenia 0/425 (0%) 1/406 (0.2%)
Cardiac disorders
Pericardial effusion 1/425 (0.2%) 1/406 (0.2%)
Acute coronary syndrome 1/425 (0.2%) 0/406 (0%)
Atrial fibrillation 1/425 (0.2%) 0/406 (0%)
Cardiac failure 1/425 (0.2%) 0/406 (0%)
Cardiac failure congestive 0/425 (0%) 1/406 (0.2%)
Cardiac tamponade 0/425 (0%) 1/406 (0.2%)
Mitral valve incompetence 1/425 (0.2%) 0/406 (0%)
Sinus arrest 1/425 (0.2%) 0/406 (0%)
Sinus bradycardia 1/425 (0.2%) 0/406 (0%)
Sinus tachycardia 1/425 (0.2%) 0/406 (0%)
Supraventricular tachycardia 0/425 (0%) 1/406 (0.2%)
Tachycardia 0/425 (0%) 1/406 (0.2%)
Ventricular fibrillation 0/425 (0%) 1/406 (0.2%)
Ear and labyrinth disorders
Vertigo 1/425 (0.2%) 0/406 (0%)
Endocrine disorders
Hypercalcaemia of malignancy 0/425 (0%) 1/406 (0.2%)
Hypothyroidism 1/425 (0.2%) 0/406 (0%)
Eye disorders
Retinal detachment 1/425 (0.2%) 0/406 (0%)
Retinal vein occlusion 0/425 (0%) 1/406 (0.2%)
Gastrointestinal disorders
Diarrhoea 17/425 (4%) 2/406 (0.5%)
Vomiting 10/425 (2.4%) 6/406 (1.5%)
Ascites 4/425 (0.9%) 5/406 (1.2%)
Nausea 4/425 (0.9%) 3/406 (0.7%)
Abdominal pain 2/425 (0.5%) 1/406 (0.2%)
Abdominal pain upper 1/425 (0.2%) 1/406 (0.2%)
Colitis 1/425 (0.2%) 1/406 (0.2%)
Constipation 1/425 (0.2%) 1/406 (0.2%)
Enterocolitis 2/425 (0.5%) 0/406 (0%)
Gastritis 0/425 (0%) 2/406 (0.5%)
Abdominal discomfort 1/425 (0.2%) 0/406 (0%)
Abdominal distension 0/425 (0%) 1/406 (0.2%)
Colonic obstruction 1/425 (0.2%) 0/406 (0%)
Dyspepsia 0/425 (0%) 1/406 (0.2%)
Enteritis 1/425 (0.2%) 0/406 (0%)
Gastrointestinal haemorrhage 0/425 (0%) 1/406 (0.2%)
Gastrointestinal hypomotility 1/425 (0.2%) 0/406 (0%)
Hiatus hernia 0/425 (0%) 1/406 (0.2%)
Ileitis 1/425 (0.2%) 0/406 (0%)
Ileus 1/425 (0.2%) 0/406 (0%)
Intestinal obstruction 0/425 (0%) 1/406 (0.2%)
Oesophagitis 1/425 (0.2%) 0/406 (0%)
General disorders
Pyrexia 3/425 (0.7%) 5/406 (1.2%)
General physical health deterioration 3/425 (0.7%) 3/406 (0.7%)
Asthenia 1/425 (0.2%) 3/406 (0.7%)
Chest pain 0/425 (0%) 2/406 (0.5%)
Fatigue 2/425 (0.5%) 0/406 (0%)
Multi-organ failure 1/425 (0.2%) 1/406 (0.2%)
Non-cardiac chest pain 1/425 (0.2%) 1/406 (0.2%)
Oedema peripheral 0/425 (0%) 2/406 (0.5%)
Pain 1/425 (0.2%) 1/406 (0.2%)
Generalised oedema 0/425 (0%) 1/406 (0.2%)
Malaise 1/425 (0.2%) 0/406 (0%)
Hepatobiliary disorders
Hepatic failure 3/425 (0.7%) 2/406 (0.5%)
Bile duct obstruction 1/425 (0.2%) 1/406 (0.2%)
Bile duct stenosis 1/425 (0.2%) 0/406 (0%)
Cholangitis 1/425 (0.2%) 0/406 (0%)
Hepatomegaly 1/425 (0.2%) 0/406 (0%)
Portal vein thrombosis 1/425 (0.2%) 0/406 (0%)
Infections and infestations
Pneumonia 4/425 (0.9%) 4/406 (1%)
Urinary tract infection 4/425 (0.9%) 3/406 (0.7%)
Bronchitis 1/425 (0.2%) 3/406 (0.7%)
Cellulitis 1/425 (0.2%) 3/406 (0.7%)
Device related infection 1/425 (0.2%) 2/406 (0.5%)
Lower respiratory tract infection 2/425 (0.5%) 1/406 (0.2%)
Lung infection 2/425 (0.5%) 1/406 (0.2%)
Sepsis 1/425 (0.2%) 2/406 (0.5%)
Escherichia sepsis 1/425 (0.2%) 1/406 (0.2%)
Gastroenteritis 1/425 (0.2%) 1/406 (0.2%)
Septic shock 1/425 (0.2%) 1/406 (0.2%)
Urosepsis 0/425 (0%) 2/406 (0.5%)
Wound infection 1/425 (0.2%) 1/406 (0.2%)
Abscess intestinal 1/425 (0.2%) 0/406 (0%)
Acute haemorrhagic conjunctivitis 1/425 (0.2%) 0/406 (0%)
Bacteraemia 0/425 (0%) 1/406 (0.2%)
Breast infection 0/425 (0%) 1/406 (0.2%)
Herpes simplex 0/425 (0%) 1/406 (0.2%)
Herpes zoster 0/425 (0%) 1/406 (0.2%)
Influenza 1/425 (0.2%) 0/406 (0%)
Klebsiella infection 1/425 (0.2%) 0/406 (0%)
Moraxella infection 1/425 (0.2%) 0/406 (0%)
Neutropenic sepsis 0/425 (0%) 1/406 (0.2%)
Oral herpes 0/425 (0%) 1/406 (0.2%)
Parainfluenzae virus infection 1/425 (0.2%) 0/406 (0%)
Pharyngitis 0/425 (0%) 1/406 (0.2%)
Pyelonephritis 1/425 (0.2%) 0/406 (0%)
Streptococcal sepsis 0/425 (0%) 1/406 (0.2%)
Wound infection staphylococcal 1/425 (0.2%) 0/406 (0%)
Injury, poisoning and procedural complications
Femoral neck fracture 0/425 (0%) 1/406 (0.2%)
Infusion related reaction 1/425 (0.2%) 0/406 (0%)
Rib fracture 1/425 (0.2%) 0/406 (0%)
Stress fracture 1/425 (0.2%) 0/406 (0%)
Subdural haemorrhage 1/425 (0.2%) 0/406 (0%)
Wound dehiscence 1/425 (0.2%) 0/406 (0%)
Investigations
Neutrophil count decreased 0/425 (0%) 2/406 (0.5%)
Blood bilirubin increased 1/425 (0.2%) 0/406 (0%)
Clostridium test positive 0/425 (0%) 1/406 (0.2%)
Metabolism and nutrition disorders
Dehydration 8/425 (1.9%) 6/406 (1.5%)
Hypercalcaemia 2/425 (0.5%) 2/406 (0.5%)
Hypokalaemia 2/425 (0.5%) 2/406 (0.5%)
Hyperkalaemia 1/425 (0.2%) 1/406 (0.2%)
Decreased appetite 1/425 (0.2%) 0/406 (0%)
Fluid overload 0/425 (0%) 1/406 (0.2%)
Hyponatraemia 1/425 (0.2%) 0/406 (0%)
Hypophosphataemia 1/425 (0.2%) 0/406 (0%)
Type 2 diabetes mellitus 0/425 (0%) 1/406 (0.2%)
Musculoskeletal and connective tissue disorders
Bone pain 1/425 (0.2%) 2/406 (0.5%)
Back pain 1/425 (0.2%) 1/406 (0.2%)
Pain in extremity 1/425 (0.2%) 1/406 (0.2%)
Pathological fracture 0/425 (0%) 2/406 (0.5%)
Flank pain 1/425 (0.2%) 0/406 (0%)
Groin pain 0/425 (0%) 1/406 (0.2%)
Muscular weakness 0/425 (0%) 1/406 (0.2%)
Musculoskeletal chest pain 0/425 (0%) 1/406 (0.2%)
Spinal osteoarthritis 0/425 (0%) 1/406 (0.2%)
Osteoporotic fracture 1/425 (0.2%) 0/406 (0%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Metastases to central nervous system 6/425 (1.4%) 10/406 (2.5%)
Metastases to meninges 2/425 (0.5%) 4/406 (1%)
Metastatic pain 2/425 (0.5%) 1/406 (0.2%)
Malignant pleural effusion 1/425 (0.2%) 1/406 (0.2%)
Breast cancer 1/425 (0.2%) 0/406 (0%)
Cancer pain 0/425 (0%) 1/406 (0.2%)
Metastases to bone 0/425 (0%) 1/406 (0.2%)
Metastases to liver 0/425 (0%) 1/406 (0.2%)
Metastases to spine 1/425 (0.2%) 0/406 (0%)
Myelodysplastic syndrome 1/425 (0.2%) 0/406 (0%)
Ovarian cancer 1/425 (0.2%) 0/406 (0%)
Nervous system disorders
Syncope 3/425 (0.7%) 1/406 (0.2%)
Brain oedema 1/425 (0.2%) 2/406 (0.5%)
Headache 2/425 (0.5%) 1/406 (0.2%)
Hepatic encephalopathy 3/425 (0.7%) 0/406 (0%)
Cerebrovascular accident 1/425 (0.2%) 0/406 (0%)
Cholinergic syndrome 1/425 (0.2%) 0/406 (0%)
Convulsion 0/425 (0%) 1/406 (0.2%)
Dizziness 1/425 (0.2%) 0/406 (0%)
Dysgraphia 1/425 (0.2%) 0/406 (0%)
Gliosis 1/425 (0.2%) 0/406 (0%)
Hydrocephalus 1/425 (0.2%) 0/406 (0%)
Neuralgia 0/425 (0%) 1/406 (0.2%)
Paraesthesia 1/425 (0.2%) 0/406 (0%)
Peripheral motor neuropathy 0/425 (0%) 1/406 (0.2%)
Spinal chord compression 0/425 (0%) 1/406 (0.2%)
Psychiatric disorders
Bipolar disorder 1/425 (0.2%) 0/406 (0%)
Confusional state 0/425 (0%) 1/406 (0.2%)
Renal and urinary disorders
Renal failure acute 3/425 (0.7%) 1/406 (0.2%)
Renal failure 2/425 (0.5%) 0/406 (0%)
Urinary incontinence 0/425 (0%) 1/406 (0.2%)
Reproductive system and breast disorders
Pelvic pain 0/425 (0%) 1/406 (0.2%)
Respiratory, thoracic and mediastinal disorders
Pleural effusion 15/425 (3.5%) 18/406 (4.4%)
Dyspnoea 2/425 (0.5%) 7/406 (1.7%)
Respiratory failure 1/425 (0.2%) 5/406 (1.2%)
Pulmonary embolism 4/425 (0.9%) 1/406 (0.2%)
Hypoxia 2/425 (0.5%) 1/406 (0.2%)
Pneumothorax 1/425 (0.2%) 1/406 (0.2%)
Acute respiratory failure 1/425 (0.2%) 0/406 (0%)
Chronic obstructive pulmonary disease 0/425 (0%) 1/406 (0.2%)
Lung infiltration 1/425 (0.2%) 0/406 (0%)
Pleurisy 0/425 (0%) 1/406 (0.2%)
Pulmonary hypertension 1/425 (0.2%) 0/406 (0%)
Respiratory distress 1/425 (0.2%) 0/406 (0%)
Skin and subcutaneous tissue disorders
Subcutaneous emphysema 0/425 (0%) 1/406 (0.2%)
Vascular disorders
Aortic stenosis 1/425 (0.2%) 0/406 (0%)
Embolism 0/425 (0%) 1/406 (0.2%)
Hypotension 0/425 (0%) 1/406 (0.2%)
Lymphoedema 0/425 (0%) 1/406 (0.2%)
Other (Not Including Serious) Adverse Events
NKTR-102 Physician's Treatment of Choice
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total 417/425 (98.1%) 404/406 (99.5%)
Blood and lymphatic system disorders
Neutropenia 92/425 (21.6%) 174 126/406 (31%) 244
Anaemia 64/425 (15.1%) 83 82/406 (20.2%) 105
Eye disorders
Vision blurred 68/425 (16%) 161 12/406 (3%) 13
Gastrointestinal disorders
Nausea 255/425 (60%) 478 155/406 (38.2%) 249
Diarrhoea 277/425 (65.2%) 1202 79/406 (19.5%) 128
Vomiting 172/425 (40.5%) 342 72/406 (17.7%) 109
Constipation 112/425 (26.4%) 167 126/406 (31%) 152
Abdominal pain 89/425 (20.9%) 147 47/406 (11.6%) 52
Abdominal pain upper 56/425 (13.2%) 71 37/406 (9.1%) 45
Dyspepsia 34/425 (8%) 45 32/406 (7.9%) 50
Stomatitis 17/425 (4%) 23 34/406 (8.4%) 43
General disorders
Fatigue 145/425 (34.1%) 241 130/406 (32%) 163
Asthenia 91/425 (21.4%) 142 114/406 (28.1%) 170
Pyrexia 30/425 (7.1%) 39 63/406 (15.5%) 98
Oedema peripheral 20/425 (4.7%) 22 42/406 (10.3%) 49
Infections and infestations
Urinary tract infection 26/425 (6.1%) 27 26/406 (6.4%) 28
Upper respiratory tract infection 15/425 (3.5%) 18 27/406 (6.7%) 32
Investigations
Weight decreased 57/425 (13.4%) 65 24/406 (5.9%) 25
Neutrophil count decreased 26/425 (6.1%) 41 50/406 (12.3%) 126
Aspartate aminotransferase increased 23/425 (5.4%) 24 29/406 (7.1%) 31
Metabolism and nutrition disorders
Decreased appetite 130/425 (30.6%) 169 98/406 (24.1%) 116
Hypokalaemia 39/425 (9.2%) 54 37/406 (9.1%) 39
Dehydration 34/425 (8%) 39 19/406 (4.7%) 25
Musculoskeletal and connective tissue disorders
Myalgia 26/425 (6.1%) 30 59/406 (14.5%) 89
Back pain 39/425 (9.2%) 45 39/406 (9.6%) 41
Arthralgia 29/425 (6.8%) 35 42/406 (10.3%) 55
Pain in extremity 27/425 (6.4%) 32 35/406 (8.6%) 43
Bone pain 17/425 (4%) 20 35/406 (8.6%) 38
Musculoskeletal pain 25/425 (5.9%) 28 26/406 (6.4%) 29
Muscle spasms 25/425 (5.9%) 28 26/406 (6.4%) 29
Musculoskeletal chest pain 16/425 (3.8%) 16 26/406 (6.4%) 31
Nervous system disorders
Dizziness 55/425 (12.9%) 75 41/406 (10.1%) 51
Dysgeusia 34/425 (8%) 41 28/406 (6.9%) 44
Neuropathy peripheral 9/425 (2.1%) 9 50/406 (12.3%) 62
Psychiatric disorders
Insomnia 29/425 (6.8%) 45 33/406 (8.1%) 35
Anxiety 20/425 (4.7%) 26 22/406 (5.4%) 23
Respiratory, thoracic and mediastinal disorders
Dyspnoea 58/425 (13.6%) 68 70/406 (17.2%) 87
Cough 59/425 (13.9%) 64 52/406 (12.8%) 55
Skin and subcutaneous tissue disorders
Alopecia 44/425 (10.4%) 49 95/406 (23.4%) 102
Rash 23/425 (5.4%) 28 24/406 (5.9%) 28

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

There are restrictions to the PI's rights to discuss or publish trial results.

Results Point of Contact

Name/Title Alison Hannah, MD
Organization Nektar
Phone
Email AHannah@nektar.com
Responsible Party:
Nektar Therapeutics
ClinicalTrials.gov Identifier:
NCT01492101
Other Study ID Numbers:
  • 11-PIR-11
First Posted:
Dec 14, 2011
Last Update Posted:
Jun 1, 2021
Last Verified:
May 1, 2021