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A Study of Etirinotecan Pegol (NKTR-102) Versus Treatment of Physician's Choice (TPC) in Patients With Metastatic Breast Cancer Who Have Stable Brain Metastases and Have Been Previously Treated With an Anthracycline, a Taxane, and Capecitabine (ATTAIN)

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ClinicalTrials.gov Identifier: NCT02915744
Recruitment Status : Completed
First Posted : September 27, 2016
Results First Posted : August 27, 2021
Last Update Posted : April 14, 2023
Sponsor:
Information provided by (Responsible Party):
Nektar Therapeutics

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Conditions Metastasis
Breast Cancer
Interventions Drug: NKTR-102
Drug: Eribulin
Drug: Ixabepilone
Drug: Vinorelbine
Drug: Gemcitabine
Drug: Paclitaxel
Drug: Docetaxel
Drug: Nab-paclitaxel
Enrollment 178
Recruitment Details  
Pre-assignment Details  
Arm/Group Title NKTR-102 Treatment of Physician's Choice (TPC)
Hide Arm/Group Description NKTR-102 will be administered at a dose level of 145 mg/m2 on a q21d schedule as a 90-minute intravenous (IV) infusion on Day 1 of each treatment cycle. TPC will be administered per standard of care. Patients randomized to TPC will receive single-agent IV chemotherapy, limited to choice of one of the following 7 agents: eribulin, ixabepilone, vinorelbine, gemcitabine, paclitaxel, docetaxel, or nab-paclitaxel.
Period Title: Overall Study
Started 92 86
Completed 13 9
Not Completed 79 77
Arm/Group Title NKTR-102 Treatment of Physician's Choice (TPC) Total
Hide Arm/Group Description NKTR-102 will be administered at a dose level of 145 mg/m2 on a q21d schedule as a 90-minute intravenous (IV) infusion on Day 1 of each treatment cycle. TPC will be administered per standard of care. Patients randomized to TPC will receive single-agent IV chemotherapy, limited to choice of one of the following 7 agents: eribulin, ixabepilone, vinorelbine, gemcitabine, paclitaxel, docetaxel, or nab-paclitaxel. Total of all reporting groups
Overall Number of Baseline Participants 92 86 178
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 92 participants 86 participants 178 participants
54.7  (10.13) 51.9  (10.50) 53.3  (10.37)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 92 participants 86 participants 178 participants
Female
92
 100.0%
86
 100.0%
178
 100.0%
Male
0
   0.0%
0
   0.0%
0
   0.0%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 92 participants 86 participants 178 participants
Hispanic or Latino
2
   2.2%
6
   7.0%
8
   4.5%
Not Hispanic or Latino
69
  75.0%
60
  69.8%
129
  72.5%
Unknown or Not Reported
21
  22.8%
20
  23.3%
41
  23.0%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 92 participants 86 participants 178 participants
American Indian or Alaska Native
0
   0.0%
0
   0.0%
0
   0.0%
Asian
3
   3.3%
6
   7.0%
9
   5.1%
Native Hawaiian or Other Pacific Islander
0
   0.0%
0
   0.0%
0
   0.0%
Black or African American
3
   3.3%
5
   5.8%
8
   4.5%
White
66
  71.7%
57
  66.3%
123
  69.1%
More than one race
0
   0.0%
0
   0.0%
0
   0.0%
Unknown or Not Reported
20
  21.7%
18
  20.9%
38
  21.3%
Eastern Cooperative Oncology Group (ECOG)   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
 Number Analyzed 92 participants 86 participants 178 participants
0
25
  27.2%
25
  29.1%
50
  28.1%
1
67
  72.8%
61
  70.9%
128
  71.9%
[1]
Measure Description:

Grade - ECOG Performance Status

  1. - Fully active, able to carry on all pre-disease performance without restriction
  2. - Restricted in physically strenuous activity but ambulatory and able to carry out work of a light or sedentary nature, e.g., light house work, office work
Reproductive Status  
Measure Type: Count of Participants
Unit of measure:  Participants
 Number Analyzed 92 participants 86 participants 178 participants
Of Child-Bearing Potential
16
  17.4%
13
  15.1%
29
  16.3%
Surgically Sterile
11
  12.0%
14
  16.3%
25
  14.0%
Post-Menopausal
65
  70.7%
55
  64.0%
120
  67.4%
Other
0
   0.0%
4
   4.7%
4
   2.2%
Missing
0
   0.0%
0
   0.0%
0
   0.0%
Pregnancy Test at Screening  
Measure Type: Count of Participants
Unit of measure:  Participants
 Number Analyzed 92 participants 86 participants 178 participants
Performed
29
  31.5%
26
  30.2%
55
  30.9%
Positive
1
   1.1%
1
   1.2%
2
   1.1%
Negative
22
  23.9%
24
  27.9%
46
  25.8%
Borderline
6
   6.5%
1
   1.2%
7
   3.9%
Not Performed
63
  68.5%
60
  69.8%
123
  69.1%
Height  
Mean (Standard Deviation)
Unit of measure:  Centimeters
Number Analyzed 92 participants 86 participants 178 participants
162.7  (6.67) 162.1  (7.73) 162.4  (7.19)
Weight  
Mean (Standard Deviation)
Unit of measure:  Kilograms
Number Analyzed 92 participants 86 participants 178 participants
67.16  (17.468) 65.97  (15.561) 66.59  (16.539)
Time since Initial Breast Cancer Diagnosis  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 92 participants 86 participants 178 participants
8.094  (5.1700) 6.950  (5.0941) 7.541  (5.151)
Breast Cancer at Initial Diagnosis   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
 Number Analyzed 92 participants 86 participants 178 participants
I
5
   5.4%
10
  11.6%
15
   8.4%
II
41
  44.6%
29
  33.7%
70
  39.3%
III
22
  23.9%
17
  19.8%
39
  21.9%
IV
10
  10.9%
16
  18.6%
26
  14.6%
Unknown
14
  15.2%
14
  16.3%
28
  15.7%
[1]
Measure Description:

Stage 1: Primary Tumor is less than or equal to 20 mm in greatest dimension

Stage 2: Primary Tumor is greater than 20 mm but no less than or equal to 50 mm in greatest dimension

Stage 3: Primary Tumor is greater than 50 mm in greatest dimension

Stage 4: Tumor of any size with direct extension to the chest wall and/or to the skin (ulceration or skin nodules)
Cancer Histology at Initial Diagnosis  
Measure Type: Count of Participants
Unit of measure:  Participants
 Number Analyzed 92 participants 86 participants 178 participants
Invasive Ductal Carcinoma
80
  87.0%
77
  89.5%
157
  88.2%
Invasive Lobular Carcinoma
6
   6.5%
1
   1.2%
7
   3.9%
Other
6
   6.5%
8
   9.3%
14
   7.9%
Estrogen Receptor Status at Initial Diagnosis  
Measure Type: Count of Participants
Unit of measure:  Participants
 Number Analyzed 92 participants 86 participants 178 participants
ER Positive
52
  56.5%
49
  57.0%
101
  56.7%
ER Negative
40
  43.5%
34
  39.5%
74
  41.6%
Unknown
0
   0.0%
3
   3.5%
3
   1.7%
Progesterone Receptor (PgR) Status at Initial Diagnosis  
Measure Type: Count of Participants
Unit of measure:  Participants
 Number Analyzed 92 participants 86 participants 178 participants
PgR Positive
40
  43.5%
42
  48.8%
82
  46.1%
PgR Negative
50
  54.3%
41
  47.7%
91
  51.1%
Unknown
2
   2.2%
3
   3.5%
5
   2.8%
Human Epidermal Growth Factor Receptor (HER2) Status at Initial Diagnosis  
Measure Type: Count of Participants
Unit of measure:  Participants
 Number Analyzed 92 participants 86 participants 178 participants
HER2 Positive
15
  16.3%
14
  16.3%
29
  16.3%
HER2 Negative
76
  82.6%
66
  76.7%
142
  79.8%
Unknown
1
   1.1%
6
   7.0%
7
   3.9%
Estrogen Receptor Status at Last Biopsy  
Measure Type: Count of Participants
Unit of measure:  Participants
 Number Analyzed 92 participants 86 participants 178 participants
ER Positive
47
  51.1%
48
  55.8%
95
  53.4%
ER Negative
38
  41.3%
36
  41.9%
74
  41.6%
Unknown
7
   7.6%
2
   2.3%
9
   5.1%
Progesterone Receptor Status at Last Biopsy  
Measure Type: Count of Participants
Unit of measure:  Participants
 Number Analyzed 92 participants 86 participants 178 participants
PgR Positive
32
  34.8%
31
  36.0%
63
  35.4%
PgR Negative
51
  55.4%
52
  60.5%
103
  57.9%
Unknown
9
   9.8%
3
   3.5%
12
   6.7%
HER2 Receptor Status at Last Biopsy  
Measure Type: Count of Participants
Unit of measure:  Participants
 Number Analyzed 92 participants 86 participants 178 participants
HER2 Positive
12
  13.0%
13
  15.1%
25
  14.0%
HER2 Negative
74
  80.4%
69
  80.2%
143
  80.3%
Unknown
6
   6.5%
4
   4.7%
10
   5.6%
Estrogen Receptor/Progesterone Receptor Status at Last Biopsy  
Measure Type: Count of Participants
Unit of measure:  Participants
 Number Analyzed 92 participants 86 participants 178 participants
ER/PgR Positive
49
  53.3%
49
  57.0%
98
  55.1%
ER/PgR Negative
36
  39.1%
35
  40.7%
71
  39.9%
Unknown
7
   7.6%
2
   2.3%
9
   5.1%
Time since Initial Brain Metastasis Diagnosis  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 92 participants 86 participants 178 participants
1.137  (1.1061) 1.194  (1.1748) 1.165  (1.1369)
1.Primary Outcome
Title Overall Survival (OS) of Patients
Hide Description To compare Overall Survival (OS) of patients who receive 145 mg/m2 NKTR-102 given once every 21 days (q21d) with OS of patients who receive Treatment of Physician's Choice (TPC). Overall survival is defined as the time from the date of randomization to the date of death from any cause. Patients will be followed until their date of death or until final database closure. Patients who are lost-to-follow-up or are alive at the time of analysis will be censored at the time they were last known to be alive or at the date of event cut-off for OS analysis.
Time Frame Within 3 years from study start
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title NKTR-102 Treatment of Physician's Choice (TPC)
Hide Arm/Group Description:
In Group A, NKTR-102 will be administered at a dose level of 145 mg/m2 on a q21d schedule as a 90-minute intravenous (IV) infusion on Day 1 of each treatment cycle.
In Group B, TPC will be administered per standard of care. Patients randomized to TPC will receive single-agent IV chemotherapy, limited to choice of one of the following 7 agents: eribulin, ixabepilone, vinorelbine, gemcitabine, paclitaxel, docetaxel, or nab-paclitaxel.
Overall Number of Participants Analyzed 92 86
Median (95% Confidence Interval)
Unit of Measure: months
7.8
(6.1 to 10.2)
7.5
(5.8 to 10.4)
2.Secondary Outcome
Title Progression-Free Survival (Outside the Central Nervous System)
Hide Description Progression-Free Survival (PFS) is defined as the time from the date of randomization to the earliest evidence of documented Progressive Disease (PD) or of death from any cause. The date of global deterioration or symptomatic deterioration will not be used as the date of PD. The assessment of PFS outside the CNS will utilize RECIST criteria v1.1.
Time Frame Through study completion, an expected average of 1 year
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title NKTR-102 Treatment of Physician's Choice (TPC)
Hide Arm/Group Description:
In Group A, NKTR-102 will be administered at a dose level of 145 mg/m2 on a q21d schedule as a 90-minute intravenous (IV) infusion on Day 1 of each treatment cycle.
In Group B, TPC will be administered per standard of care. Patients randomized to TPC will receive single-agent IV chemotherapy, limited to choice of one of the following 7 agents: eribulin, ixabepilone, vinorelbine, gemcitabine, paclitaxel, docetaxel, or nab-paclitaxel.
Overall Number of Participants Analyzed 92 86
Median (95% Confidence Interval)
Unit of Measure: months
2.8
(2.0 to 4.1)
1.9
(1.9 to 2.1)
3.Secondary Outcome
Title Progression-Free Survival in Brain Metastasis (PFS-BM)
Hide Description Progression-Free Survival in Brain Metastasis (PFS-BM) is defined as the time from the date of randomization to the earliest evidence of documented Progressive Disease (PD) per Response Assessment in Neuro-Oncology-Brain Metastases (RANO-BM) in brain metastases or death from any cause. The PD will also be determined by the investigator's assessments. Progressive Disease (PD) is defined as at least a 20% increase in the sum of longest diameters of CNS target lesions, taking as reference the smallest sum on study. This included the baseline sum if that was the smallest on study. In addition to the relative increase of 20%, at least 1 lesion had to increase by an absolute value of 5 mm or more to be considered progression.
Time Frame Through study completion, an expected average of 1 year
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title NKTR-102 Treatment of Physician's Choice (TPC)
Hide Arm/Group Description:
In Group A, NKTR-102 will be administered at a dose level of 145 mg/m2 on a q21d schedule as a 90-minute intravenous (IV) infusion on Day 1 of each treatment cycle.
In Group B, TPC will be administered per standard of care. Patients randomized to TPC will receive single-agent IV chemotherapy, limited to choice of one of the following 7 agents: eribulin, ixabepilone, vinorelbine, gemcitabine, paclitaxel, docetaxel, or nab-paclitaxel.
Overall Number of Participants Analyzed 92 86
Median (95% Confidence Interval)
Unit of Measure: months
3.9
(2.6 to 4.3)
3.3
(1.9 to 3.7)
4.Secondary Outcome
Title Progression-Free Survival (Overall)
Hide Description Progression-free survival (CNS and peripheral) is defined as the time from the date of randomization to the earliest evidence of documented PD in either the CNS or peripheral (using RANO-BM) or death from any cause. The PD will be determined by both the investigator's and the central imaging facility assessments. The same statistical methods that were used for PFS and PFS-BM will be used for PFS (Overall). Progressive Disease (PD) is defined as at least a 20% increase in the sum of longest diameters of CNS target lesions, taking as reference the smallest sum on study. This included the baseline sum if that was the smallest on study. In addition to the relative increase of 20%, at least 1 lesion had to increase by an absolute value of 5 mm or more to be considered progression.
Time Frame Through study completion, an expected average of 1 year
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title NKTR-102 Treatment of Physician's Choice (TPC)
Hide Arm/Group Description:
In Group A, NKTR-102 will be administered at a dose level of 145 mg/m2 on a q21d schedule as a 90-minute intravenous (IV) infusion on Day 1 of each treatment cycle.
In Group B, TPC will be administered per standard of care. Patients randomized to TPC will receive single-agent IV chemotherapy, limited to choice of one of the following 7 agents: eribulin, ixabepilone, vinorelbine, gemcitabine, paclitaxel, docetaxel, or nab-paclitaxel.
Overall Number of Participants Analyzed 92 86
Median (95% Confidence Interval)
Unit of Measure: months
2.1
(1.9 to 3.7)
1.9
(1.8 to 2.0)
5.Secondary Outcome
Title Objective Response Rates (ORR) of the NKTR-102 Treatment and the Treatment of Physician's Choice (TPC)
Hide Description RECIST criteria for lesions outside the Central Nervous System (CNS); RANO-BM criteria for CNS lesions) based upon the best response as assessed by the central imaging facility. CR is defined as disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) had to have reduction in short axis to < 10 mm. PR is defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. ORR is calculated as the sum of CR and PR. Progressive Disease (PD) is defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this included the baseline sum if that was the smallest on study). Stable Disease (SD) is defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study.
Time Frame Through study completion, an expected average of 1 year
Hide Outcome Measure Data
Hide Analysis Population Description
156 patients had measurable disease by RECIST v 1.1 at baseline and were included in the Response Evaluable population for this outcome.
Arm/Group Title NKTR-102 Treatment of Physician's Choice (TPC)
Hide Arm/Group Description:
In Group A, NKTR-102 will be administered at a dose level of 145 mg/m2 on a q21d schedule as a 90-minute intravenous (IV) infusion on Day 1 of each treatment cycle.
In Group B, TPC will be administered per standard of care. Patients randomized to TPC will receive single-agent IV chemotherapy, limited to choice of one of the following 7 agents: eribulin, ixabepilone, vinorelbine, gemcitabine, paclitaxel, docetaxel, or nab-paclitaxel.
Overall Number of Participants Analyzed 83 73
Measure Type: Count of Participants
Unit of Measure: Participants
Objective Response Rate (CR+PR)
4
   4.8%
2
   2.7%
Stable Disease
16
  19.3%
5
   6.8%
Progressive Disease
38
  45.8%
32
  43.8%
Not Evaluable
18
  21.7%
30
  41.1%
Missing
7
   8.4%
4
   5.5%
6.Secondary Outcome
Title Clinical Benefit Rate (CBR)
Hide Description Clinical Benefit Rate will be defined as the proportion of patients having a Complete Response (CR), Partial Response (PR), or Stable Disease (SD) for at least 4 months (≥ 120 days). CR is defined as disappearance of all target lesions for at least 4 weeks with no new lesions, not use of corticosteroids, and patient was stable or improved clinically. PR is defined as at least a 30% decrease in the sum of longest diameters sustained for at least 4 weeks, no new lesions; stable to decreased corticosteroid dose; stable or improved clinically. Progressive Disease (PD) is defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this included the baseline sum if that was the smallest on study). Stable Disease (SD) is defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study.
Time Frame For at least 4 months, with an expected average of 1 year
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title NKTR-102 Treatment of Physician's Choice (TPC)
Hide Arm/Group Description:
In Group A, NKTR-102 will be administered at a dose level of 145 mg/m2 on a q21d schedule as a 90-minute intravenous (IV) infusion on Day 1 of each treatment cycle.
In Group B, TPC will be administered per standard of care. Patients randomized to TPC will receive single-agent IV chemotherapy, limited to choice of one of the following 7 agents: eribulin, ixabepilone, vinorelbine, gemcitabine, paclitaxel, docetaxel, or nab-paclitaxel.
Overall Number of Participants Analyzed 92 86
Measure Type: Number
Unit of Measure: participants
# of Patients who achieved Complete Response 0 0
# of Patients who achieved Partial Response 6 6
# of Patients who have Stable Disease >= 120 days 17 5
# of Patients who achieved Clinical Benefit Rate (CBR) 23 11
7.Secondary Outcome
Title Duration of Response (DoR)
Hide Description Duration of response (DoR) outside the CNS will be defined as the time from first documented CR or PR until the earliest evidence of disease progression per RECIST v1.1 or death from any cause. CR is defined as disappearance of all target lesions for at least 4 weeks with no new lesions, not use of corticosteroids, and patient was stable or improved clinically. PR is defined as at least a 30% decrease in the sum of longest diameters sustained for at least 4 weeks, no new lesions; stable to decreased corticosteroid dose; stable or improved clinically. Progressive Disease (PD) is defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this included the baseline sum if that was the smallest on study). Stable Disease (SD) is defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study.
Time Frame Through study completion, an expected average of 1 year
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title NKTR-102 Treatment of Physician's Choice (TPC)
Hide Arm/Group Description:
In Group A, NKTR-102 will be administered at a dose level of 145 mg/m2 on a q21d schedule as a 90-minute intravenous (IV) infusion on Day 1 of each treatment cycle.
In Group B, TPC will be administered per standard of care. Patients randomized to TPC will receive single-agent IV chemotherapy, limited to choice of one of the following 7 agents: eribulin, ixabepilone, vinorelbine, gemcitabine, paclitaxel, docetaxel, or nab-paclitaxel.
Overall Number of Participants Analyzed 83 73
Median (Inter-Quartile Range)
Unit of Measure: months
7.4
(7.3 to 16.4)
3.5
(3.5 to 3.5)
8.Secondary Outcome
Title Compare Health-Related Quality of Life (HRQoL) Using the European Organisation for Treatment of Cancer (EORTC) Quality of Life Core 30 (QLQ-C30) Module With the Brain Neoplasms 20-question (BN-20) Subscale.
Hide Description The EORTC QLQ-BN20 Scale has a series of 20 questions each of which involve reporting a scale from 1-4. It is an increasing scale where a score of one indicates "not at all" while a score of four indicates "very much". The minimum score is 20 and the maximum score is 80. The higher the score the worse the outcome.
Time Frame Baseline (prior to first dose of study treatment in Cycle 1 [cycle length = 21 for NKTR-102 or 28 days for TPC] and end of Cycle 44.
Hide Outcome Measure Data
Hide Analysis Population Description
As the trial progressed, some patients discontinued study treatment as a result of progressive disease, non-PD AE, patient decision, or physician decision.
Arm/Group Title NKTR-102 Treatment of Physician's Choice (TPC)
Hide Arm/Group Description:
In Group A, NKTR-102 will be administered at a dose level of 145 mg/m2 on a q21d schedule as a 90-minute intravenous (IV) infusion on Day 1 of each treatment cycle.
In Group B, TPC will be administered per standard of care. Patients randomized to TPC will receive single-agent IV chemotherapy, limited to choice of one of the following 7 agents: eribulin, ixabepilone, vinorelbine, gemcitabine, paclitaxel, docetaxel, or nab-paclitaxel.
Overall Number of Participants Analyzed 79 63
Mean (Standard Deviation)
Unit of Measure: Units on a Scale
QLQ-C30 Score at Baseline Number Analyzed 79 participants 63 participants
57.59  (21.607) 52.25  (24.236)
QLQ-C30 Score at End of Treatment, approximately 1 year Number Analyzed 44 participants 35 participants
46.97  (24.582) 52.38  (24.801)
9.Secondary Outcome
Title Compare Health-Related Quality of Life (HRQoL) Using the the EuroQoL 5D (EQ-5D-5L™)
Hide Description The EQ-5D-5L scale is used to measure health by having a patient answer a series of questions. There are a series of 5 questions each of which is scaled from a score of 4-20 in increasing increments of 4. The scale is numbered from 0 to 100 where 100 means the beast health you can imagine and 0 means the worst health.
Time Frame Baseline (prior to first dose of study treatment in Cycle 1 [cycle length = 21 for NKTR-102 or 28 days for TPC] and end of Cycle 44
Hide Outcome Measure Data
Hide Analysis Population Description
As the trial progressed, some patients discontinued study treatment as a result of progressive disease, non-PD AE, patient decision, or physician decision.
Arm/Group Title NKTR-102 Treatment of Physician's Choice (TPC)
Hide Arm/Group Description:
In Group A, NKTR-102 will be administered at a dose level of 145 mg/m2 on a q21d schedule as a 90-minute intravenous (IV) infusion on Day 1 of each treatment cycle.
In Group B, TPC will be administered per standard of care. Patients randomized to TPC will receive single-agent IV chemotherapy, limited to choice of one of the following 7 agents: eribulin, ixabepilone, vinorelbine, gemcitabine, paclitaxel, docetaxel, or nab-paclitaxel.
Overall Number of Participants Analyzed 80 63
Mean (Standard Deviation)
Unit of Measure: Units on a Scale
EQ-5D-5L Score at Baseline Number Analyzed 80 participants 63 participants
61.41  (19.739) 60.33  (23.004)
EQ-5D-5L Score at End of Treatment, approximately 1 year Number Analyzed 45 participants 35 participants
56.53  (23.467) 61.60  (20.858)
10.Secondary Outcome
Title Compare Health-Related Quality of Life (HRQoL) Using the Brief Fatigue Inventory (BFI)
Hide Description The Brief Fatigue Inventory scale utilizes a series of 4 questions. The first three are scored with a scale from 1-10. The fourth question has 6 six sub components each of which are scored with a scale of 1-10. For every scale, a score of 0 indicates no fatigue/interference where a score of 10 indicates as bad as you can imagine. A patient's score can range from 0 to 100 where 0 indicates the best outcome and 100 indicates the worst.
Time Frame Baseline (prior to first dose of study treatment in Cycle 1 [cycle length = 21 for NKTR-102 or 28 days for TPC] and end of Cycle 44
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Hide Analysis Population Description
As the trial progressed, some patients discontinued study treatment as a result of progressive disease, non-PD AE, patient decision, or physician decision.
Arm/Group Title NKTR-102 Treatment of Physician's Choice (TPC)
Hide Arm/Group Description:
In Group A, NKTR-102 will be administered at a dose level of 145 mg/m2 on a q21d schedule as a 90-minute intravenous (IV) infusion on Day 1 of each treatment cycle.
In Group B, TPC will be administered per standard of care. Patients randomized to TPC will receive single-agent IV chemotherapy, limited to choice of one of the following 7 agents: eribulin, ixabepilone, vinorelbine, gemcitabine, paclitaxel, docetaxel, or nab-paclitaxel.
Overall Number of Participants Analyzed 79 62
Mean (Standard Deviation)
Unit of Measure: Units on a Scale
BFI Score at Baseline Number Analyzed 79 participants 62 participants
4.18  (2.264) 4.04  (2.401)
BFI Score at End of Treatment, approximately 1 year Number Analyzed 42 participants 34 participants
4.83  (2.476) 4.74  (2.373)
11.Secondary Outcome
Title Magnitude of Clinical Benefit Assessed by ESMO-MCBS Derived From Overall Survival
Hide Description The magnitude of clinical benefit of NKTR-102 is assessed by the European Society for Medical Oncology Magnitude of Clinical Benefit Scale (ESMO-MCBS) (v1.0). The scale is graded 5, 4, 3, 2, 1, where grades 5 and 4 represent a high level of proven clinical benefit, and grade 1 represents no clinical benefit. To determine the magnitude of clinical benefit when the median OS with the standard of treatment is ≤ 1 year, the score is derived from the Hazard Ratio (HR) of Overall Survival, overall survival gain, and QoL improvement between two treatment arms. Values reported in the data table are Overall Survival values.
Time Frame Through study completion, within 3 years from study start
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Hide Analysis Population Description
[Not Specified]
Arm/Group Title NKTR-102 Treatment of Physician's Choice (TPC)
Hide Arm/Group Description:
NKTR-102 will be administered at a dose level of 145 mg/m2 on a q21d schedule as a 90-minute intravenous (IV) infusion on Day 1 of each treatment cycle.
In Group B, TPC will be administered per standard of care. Patients randomized to TPC will receive single-agent IV chemotherapy, limited to choice of one of the following 7 agents: eribulin, ixabepilone, vinorelbine, gemcitabine, paclitaxel, docetaxel, or nab-paclitaxel.
Overall Number of Participants Analyzed 92 86
Median (95% Confidence Interval)
Unit of Measure: months
7.8
(6.1 to 10.2)
7.5
(5.8 to 10.4)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection NKTR-102, Treatment of Physician's Choice (TPC)
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Method of Estimation Estimation Parameter ESMO-MCBS (v1.0)
Estimated Value 1
Estimation Comments [Not Specified]
12.Secondary Outcome
Title Number of Participants With Adverse Events as Assessed by Common Terminology Criteria for Adverse Events (CTCAE) v4.3
Hide Description The number of participants with adverse events as assessed by Common Terminology Criteria for Adverse Events (CTCAE) v4.3
Time Frame Through study completion, an expected average of 1 year
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Hide Analysis Population Description
167 patients received at least one dose of study treatment and were included in the Safety population for this outcome.
Arm/Group Title NKTR-102 Treatment of Physician's Choice (TPC)
Hide Arm/Group Description:
In Group A, NKTR-102 will be administered at a dose level of 145 mg/m2 on a q21d schedule as a 90-minute intravenous (IV) infusion on Day 1 of each treatment cycle.
In Group B, TPC will be administered per standard of care. Patients randomized to TPC will receive single-agent IV chemotherapy, limited to choice of one of the following 7 agents: eribulin, ixabepilone, vinorelbine, gemcitabine, paclitaxel, docetaxel, or nab-paclitaxel.
Overall Number of Participants Analyzed 90 77
Measure Type: Count of Participants
Unit of Measure: Participants
90
 100.0%
76
  98.7%
Time Frame The adverse event data was collected over the entire course of the study or approximately 2 years and 8 months.
Adverse Event Reporting Description 167 patients received at least one dose of study treatment and were included in the Safety population.
 
Arm/Group Title NKTR-102 Treatment of Physician's Choice (TPC)
Hide Arm/Group Description In Group A, NKTR-102 will be administered at a dose level of 145 mg/m2 on a q21d schedule as a 90-minute intravenous (IV) infusion on Day 1 of each treatment cycle. In Group B, TPC will be administered per standard of care. Patients randomized to TPC will receive single-agent IV chemotherapy, limited to choice of one of the following 7 agents: eribulin, ixabepilone, vinorelbine, gemcitabine, paclitaxel, docetaxel, or nab-paclitaxel.
All-Cause Mortality
NKTR-102 Treatment of Physician's Choice (TPC)
Affected / at Risk (%) Affected / at Risk (%)
Total   2/90 (2.22%)   0/77 (0.00%) 
Hide Serious Adverse Events
NKTR-102 Treatment of Physician's Choice (TPC)
Affected / at Risk (%) Affected / at Risk (%)
Total   33/90 (36.67%)   24/77 (31.17%) 
Blood and lymphatic system disorders     
Febrile Neutropenia Grade 3 †  0/90 (0.00%)  1/77 (1.30%) 
Cardiac disorders     
Atrial Fibrillation Grade 3 †  1/90 (1.11%)  0/77 (0.00%) 
Cardiac Tamponade Grade 4 †  0/90 (0.00%)  1/77 (1.30%) 
Eye disorders     
Blindness Grade 3 †  0/90 (0.00%)  1/77 (1.30%) 
Gastrointestinal disorders     
Colitis Grade 2 †  1/90 (1.11%)  0/77 (0.00%) 
Esophagitis Grade 3 †  1/90 (1.11%)  0/77 (0.00%) 
Vomiting Grade 2 †  3/90 (3.33%)  1/77 (1.30%) 
Diarrhea Grade 3 †  5/90 (5.56%)  0/77 (0.00%) 
Intestinal Obstruction Grade 3 †  1/90 (1.11%)  0/77 (0.00%) 
Nausea Grade 2 †  0/90 (0.00%)  1/77 (1.30%) 
Colitis Grade 3 †  3/90 (3.33%)  0/77 (0.00%) 
Vomiting Grade 3 †  0/90 (0.00%)  1/77 (1.30%) 
Neutropenic Colitis Grade 4 †  1/90 (1.11%)  0/77 (0.00%) 
General disorders     
Abdominal Pain Grade 2 †  0/90 (0.00%)  1/77 (1.30%) 
Dysphagia Grade 3 †  0/90 (0.00%)  1/77 (1.30%) 
Abdominal Pain Grade 3 †  0/90 (0.00%)  1/77 (1.30%) 
Generalized Physical Health Deterioration Grade 3 †  1/90 (1.11%)  0/77 (0.00%) 
Generalized Physical Health Deterioration Grade 5 †  1/90 (1.11%)  0/77 (0.00%) 
Asthenia Grade 3 †  1/90 (1.11%)  0/77 (0.00%) 
Fatigue Grade 3 †  0/90 (0.00%)  1/77 (1.30%) 
Hepatobiliary disorders     
Hyperbilirubinemia †  0/90 (0.00%)  2/77 (2.60%) 
Bile Duct Stone Grade 3 †  1/90 (1.11%)  0/77 (0.00%) 
Cholecystitis Grade 3 †  1/90 (1.11%)  0/77 (0.00%) 
Hepatic Function Abnormal Grade 3 †  1/90 (1.11%)  0/77 (0.00%) 
Hepatic Failure Grade 3 †  0/90 (0.00%)  1/77 (1.30%) 
Hyperbilirubinemia Grade 3 †  0/90 (0.00%)  2/77 (2.60%) 
Immune system disorders     
Leukopenia Grade 4 †  1/90 (1.11%)  0/77 (0.00%) 
Neutropenia Grade 4 †  3/90 (3.33%)  0/77 (0.00%) 
Normochromic normocytic Anemia Grade 3 †  0/90 (0.00%)  1/77 (1.30%) 
Infections and infestations     
Pneumonia Grade 3 †  1/90 (1.11%)  1/77 (1.30%) 
Device Related Infection Grade 4 †  1/90 (1.11%)  0/77 (0.00%) 
Neutropenic Sepsis Grade 3 †  1/90 (1.11%)  0/77 (0.00%) 
Viral Gastroenteritis Grade 3 †  1/90 (1.11%)  0/77 (0.00%) 
Urinary Tract Infection Grade 3 †  1/90 (1.11%)  1/77 (1.30%) 
Esophageal Candidiasis Grade 3 †  0/90 (0.00%)  1/77 (1.30%) 
Bacteremia Grade 4 †  0/90 (0.00%)  1/77 (1.30%) 
Pneumonia Grade 5 †  1/90 (1.11%)  0/77 (0.00%) 
Cellulitis Grade 3 †  1/90 (1.11%)  0/77 (0.00%) 
Device Related Sepsis Grade 4 †  1/90 (1.11%)  0/77 (0.00%) 
Lung Infection Grade 3 †  1/90 (1.11%)  0/77 (0.00%) 
Escherichia Sepsis Grade 3 †  0/90 (0.00%)  1/77 (1.30%) 
Pyoderma Grade 3 †  0/90 (0.00%)  1/77 (1.30%) 
Influenza Grade 4 †  1/90 (1.11%)  0/77 (0.00%) 
Injury, poisoning and procedural complications     
Fall Grade 3 †  0/90 (0.00%)  1/77 (1.30%) 
Investigations     
Neutrophil Count Decrease Grade 4 †  0/90 (0.00%)  1/77 (1.30%) 
Metabolism and nutrition disorders     
Hyponatremia Grade 3 †  1/90 (1.11%)  1/77 (1.30%) 
Dehydration Grade 3 †  2/90 (2.22%)  0/77 (0.00%) 
Failure to Thrive Grade 3 †  0/90 (0.00%)  1/77 (1.30%) 
Hypercalcemia Grade 3 †  0/90 (0.00%)  1/77 (1.30%) 
Musculoskeletal and connective tissue disorders     
Hip Fracture Grade 3 †  1/90 (1.11%)  2/77 (2.60%) 
Fatigue Grade 2 †  0/90 (0.00%)  1/77 (1.30%) 
Contusion Grade 3 †  0/90 (0.00%)  1/77 (1.30%) 
Groin Pain Grade 2 †  1/90 (1.11%)  0/77 (0.00%) 
Muscle Spasm Grade 3 †  1/90 (1.11%)  0/77 (0.00%) 
Pathological Fracture Grade 3 †  1/90 (1.11%)  0/77 (0.00%) 
Back Pain Grade 3 †  0/90 (0.00%)  1/77 (1.30%) 
Paresthesia Grade 2 †  1/90 (1.11%)  0/77 (0.00%) 
Nervous system disorders     
Brain Edema Grade 3 †  1/90 (1.11%)  0/77 (0.00%) 
Malaise Grade 3 †  1/90 (1.11%)  0/77 (0.00%) 
Dizziness Grade 3 †  1/90 (1.11%)  0/77 (0.00%) 
Epilepsy Grade 2 †  1/90 (1.11%)  0/77 (0.00%) 
Fine motor skill dysfunction Grade 2 †  1/90 (1.11%)  0/77 (0.00%) 
Hypoesthesia Grade 2 †  1/90 (1.11%)  0/77 (0.00%) 
Seizure Grade 2 †  1/90 (1.11%)  1/77 (1.30%) 
Syncope Grade 3 †  1/90 (1.11%)  0/77 (0.00%) 
Status Epilepticus Grade 3 †  0/90 (0.00%)  1/77 (1.30%) 
Psychiatric disorders     
Confusional State Grade 2 †  1/90 (1.11%)  0/77 (0.00%) 
Confusional State Grade 3 †  0/90 (0.00%)  1/77 (1.30%) 
Mental Status Changes Grade 3 †  1/90 (1.11%)  0/77 (0.00%) 
Hallucination Grade 4 †  0/90 (0.00%)  1/77 (1.30%) 
Respiratory, thoracic and mediastinal disorders     
Pleural Effusion Grade 3 †  1/90 (1.11%)  1/77 (1.30%) 
Pneumothorax Grade 2 †  1/90 (1.11%)  0/77 (0.00%) 
Dyspnea Grade 2 †  0/90 (0.00%)  1/77 (1.30%) 
Dyspnea Grade 3 †  0/90 (0.00%)  1/77 (1.30%) 
Vascular disorders     
Deep Vein Thrombosis Grade 4 †  0/90 (0.00%)  1/77 (1.30%) 
†
Indicates events were collected by systematic assessment
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
NKTR-102 Treatment of Physician's Choice (TPC)
Affected / at Risk (%) Affected / at Risk (%)
Total   90/90 (100.00%)   76/77 (98.70%) 
Blood and lymphatic system disorders     
Neutropenia †  17/90 (18.89%)  18/77 (23.38%) 
Anemia †  11/90 (12.22%)  17/77 (22.08%) 
Thrombocytopenia †  5/90 (5.56%)  5/77 (6.49%) 
Leukopenia †  5/90 (5.56%)  3/77 (3.90%) 
Eye disorders     
Vision Blurred †  10/90 (11.11%)  2/77 (2.60%) 
Gastrointestinal disorders     
Diarrhea †  66/90 (73.33%)  15/77 (19.48%) 
Constipation †  24/90 (26.67%)  20/77 (25.97%) 
Stomatitis †  4/90 (4.44%)  5/77 (6.49%) 
Abdominal Distension †  7/90 (7.78%)  1/77 (1.30%) 
Flatulence †  5/90 (5.56%)  1/77 (1.30%) 
Dyspepsia †  5/90 (5.56%)  0/77 (0.00%) 
Pyrexia †  6/90 (6.67%)  7/77 (9.09%) 
Oedema Peripheral †  6/90 (6.67%)  5/77 (6.49%) 
General disorders     
Nausea †  54/90 (60.00%)  31/77 (40.26%) 
Vomiting †  34/90 (37.78%)  17/77 (22.08%) 
Fatigue †  36/90 (40.00%)  26/77 (33.77%) 
Asthenia †  28/90 (31.11%)  16/77 (20.78%) 
Pain †  5/90 (5.56%)  4/77 (5.19%) 
Infections and infestations     
Stomatitis †  4/90 (4.44%)  5/77 (6.49%) 
Urinary Tract Infection †  8/90 (8.89%)  3/77 (3.90%) 
Investigations     
Neutrophil Count Decreased †  6/90 (6.67%)  10/77 (12.99%) 
Aspartate Aminotransferase Increased †  5/90 (5.56%)  9/77 (11.69%) 
Weight Decreased †  13/90 (14.44%)  1/77 (1.30%) 
Alanine Aminotransferase Increased †  2/90 (2.22%)  9/77 (11.69%) 
Platelet Count Decresed †  3/90 (3.33%)  4/77 (5.19%) 
White Blood Cell Count Decreased †  2/90 (2.22%)  4/77 (5.19%) 
Metabolism and nutrition disorders     
Decreased Appetite †  33/90 (36.67%)  14/77 (18.18%) 
Hypokalemia †  16/90 (17.78%)  4/77 (5.19%) 
Dehydration †  9/90 (10.00%)  1/77 (1.30%) 
Hypocalcemia †  8/90 (8.89%)  1/77 (1.30%) 
Hypoalbuminemia †  5/90 (5.56%)  1/77 (1.30%) 
Musculoskeletal and connective tissue disorders     
Abdominal Pain †  19/90 (21.11%)  11/77 (14.29%) 
Upper Abdominal Pain †  6/90 (6.67%)  3/77 (3.90%) 
Arthralgia †  5/90 (5.56%)  9/77 (11.69%) 
Pain in Extremity †  6/90 (6.67%)  8/77 (10.39%) 
Back Pain †  5/90 (5.56%)  7/77 (9.09%) 
Muscle Spasms †  8/90 (8.89%)  2/77 (2.60%) 
Myalgia †  2/90 (2.22%)  8/77 (10.39%) 
Muscle Weakness †  5/90 (5.56%)  3/77 (3.90%) 
Bone Pain †  5/90 (5.56%)  1/77 (1.30%) 
Musculoskeletal Pain †  0/90 (0.00%)  4/77 (5.19%) 
Nervous system disorders     
Headache †  18/90 (20.00%)  9/77 (11.69%) 
Dizziness †  9/90 (10.00%)  4/77 (5.19%) 
Neuropathy Peripheral †  3/90 (3.33%)  9/77 (11.69%) 
Dygeusia †  7/90 (7.78%)  2/77 (2.60%) 
Seizure †  2/90 (2.22%)  4/77 (5.19%) 
Psychiatric disorders     
Insomnia †  8/90 (8.89%)  5/77 (6.49%) 
Anxiety †  2/90 (2.22%)  6/77 (7.79%) 
Depression †  6/90 (6.67%)  2/77 (2.60%) 
Respiratory, thoracic and mediastinal disorders     
Dyspnea †  11/90 (12.22%)  14/77 (18.18%) 
Cough †  9/90 (10.00%)  7/77 (9.09%) 
Oropharyngeal Pain †  5/90 (5.56%)  1/77 (1.30%) 
Skin and subcutaneous tissue disorders     
Alopecia †  10/90 (11.11%)  9/77 (11.69%) 
Pruritus †  6/90 (6.67%)  4/77 (5.19%) 
Rash †  3/90 (3.33%)  5/77 (6.49%) 
†
Indicates events were collected by systematic assessment
[Not Specified]
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
There are restrictions to the PI's rights to discuss or publish trial results.
Results Point of Contact
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Name/Title: Study Director
Organization: Nektar Therapeutics
Phone: 855-482-8676
EMail: StudyInquiry@nektar.com
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Layout table for additonal information
Responsible Party: Nektar Therapeutics
ClinicalTrials.gov Identifier: NCT02915744    
Other Study ID Numbers: 15-102-14
First Submitted: September 22, 2016
First Posted: September 27, 2016
Results First Submitted: July 6, 2021
Results First Posted: August 27, 2021
Last Update Posted: April 14, 2023