Tumor, Breast Cancer
Conditions
Brief summary
This is a multicenter, open-label, two-arm, 2-stage, Phase 2 study of NKTR-102 in patients with metastatic or locally advanced breast cancer whose disease has failed prior taxane-based treatment in the metastatic setting. Patients will be randomized 1:1 into one of two treatment arms. NKTR 102 will be administered at a dose level of 145 mg/m2 in both arms. In Arm A, NKTR-102 will be given on a q14d schedule. In Arm B, NKTR-102 will be given on a q21d schedule. Approximately 70 patients may be evaluated in this study with approximately 35 patients enrolled in each treatment arm.
Interventions
DRUGNKTR-102
NKTR-102 given on a q14 day schedule
Sponsors
Nektar Therapeutics
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Inoperable metastatic or locally advanced breast cancer 2. No more than 2 prior chemotherapy regimens given in a metastatic or locally advanced setting and prior treatment in the metastatic setting must have included a taxane
Exclusion criteria
1. Patients who have had chemotherapy or radiotherapy within 4 weeks (6 weeks for nitrosoureas or mitomycin C) prior to Day 1 of Cycle 1 2. Patients who have had any major surgery within 4 weeks prior to Day 1 of Cycle or minor surgery within 2 weeks prior to Day 1 of Cycle 1
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Objective Response Rate (ORR) | Up to 2 years. | Per Response Evaluation Criteria In Solid Tumors (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), at least a 30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Kaplan Meier Estimate of Progression-Free Survival (PFS) | Up to 2 years. | Progression was defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions, or similar definition as accurate and appropriate. |
| Kaplan Meier Estimate of Overall Survival (OS) | Up to 2 years. | OS was calculated as the time from the date of first study drug administration until death from any cause. Subjects alive at the time of analysis were censored at the time they were last known alive. OS was analyzed for the ITT population. |
| Kaplan Meier Estimate of 6-month Survival | From Cycle 1 Day 1 to the end of 6 months. | Six-month survival (i.e., overall survival proportion at 6 months) was estimated using Kaplan Meier method. The analyses were performed in the ITT population. |
| Kaplan Meier Estimate of 1-year Survival | From Cycle 1 Day 1 to the end of 12 months. | One year survival (i.e., overall survival proportion at 12 months) was estimated using Kaplan Meier method. The analyses were performed in the ITT population. |
| Percent of Patients With Treatment-Emergent Adverse Events (TEAE): NCI-CTCAE Grade 3 or Higher With Incidence Rate ≥ 2% in Either Treatment Group | Up to 2 years. | An adverse event (AE) was defined as any untoward medical occurrence associated with the use of a drug in humans, whether or not considered drug related. An AE could therefore have been any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of an investigational product, whether or not thought to be related to the investigational product. TEAE was any event not present before exposure to the study drug or any event already present that worsened in either intensity or frequency after exposure to the study drug. All AEs were assessed for severity using the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) Version 3.0. If a particular AE was not listed in the NCI CTCAE Version 3.0, the following criteria were used: Grade 1 = Mild; Grade 2 = Moderate; Grade 3 = Severe; Grade 4 = Life threatening or disabling; Grade 5 = Death. |
Countries
Belgium, United Kingdom, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| NKTR-102 14 Day NKTR-102
NKTR-102: NKTR-102 given on a q14 day schedule | 35 |
| NKTR-102 21 Days NKTR-102
NKTR-102: NKTR-102 given on a q21 day schedule | 35 |
| Total | 70 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Death | 27 | 23 |
| Overall Study | Terminated by sponsor | 8 | 12 |
Baseline characteristics
| Characteristic | NKTR-102 14 Day | NKTR-102 21 Days | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 6 Participants | 7 Participants | 13 Participants |
| Age, Categorical Between 18 and 65 years | 29 Participants | 28 Participants | 57 Participants |
| Age, Continuous | 53.1 years STANDARD_DEVIATION 12.3 | 55.8 years STANDARD_DEVIATION 10.5 | 54.5 years STANDARD_DEVIATION 0 |
| Region of Enrollment Belgium | 14 participants | 12 participants | 26 participants |
| Region of Enrollment United Kingdom | 14 participants | 13 participants | 27 participants |
| Region of Enrollment United States | 7 participants | 10 participants | 17 participants |
| Sex: Female, Male Female | 34 Participants | 35 Participants | 69 Participants |
| Sex: Female, Male Male | 1 Participants | 0 Participants | 1 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 27 / 35 | 23 / 35 |
| other Total, other adverse events | 35 / 35 | 35 / 35 |
| serious Total, serious adverse events | 18 / 35 | 15 / 35 |
Outcome results
Primary
Objective Response Rate (ORR)
Per Response Evaluation Criteria In Solid Tumors (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), at least a 30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.
Time frame: Up to 2 years.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| NKTR-102 14 Day | Objective Response Rate (ORR) | 28.6 percentage of subjects |
| NKTR-102 21 Days | Objective Response Rate (ORR) | 35 percentage of subjects |
Secondary
Kaplan Meier Estimate of 1-year Survival
One year survival (i.e., overall survival proportion at 12 months) was estimated using Kaplan Meier method. The analyses were performed in the ITT population.
Time frame: From Cycle 1 Day 1 to the end of 12 months.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| NKTR-102 14 Day | Kaplan Meier Estimate of 1-year Survival | 42.9 percentage of subjects |
| NKTR-102 21 Days | Kaplan Meier Estimate of 1-year Survival | 51.4 percentage of subjects |
Secondary
Kaplan Meier Estimate of 6-month Survival
Six-month survival (i.e., overall survival proportion at 6 months) was estimated using Kaplan Meier method. The analyses were performed in the ITT population.
Time frame: From Cycle 1 Day 1 to the end of 6 months.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| NKTR-102 14 Day | Kaplan Meier Estimate of 6-month Survival | 57.1 percentage of subjects |
| NKTR-102 21 Days | Kaplan Meier Estimate of 6-month Survival | 82.9 percentage of subjects |
Secondary
Kaplan Meier Estimate of Overall Survival (OS)
OS was calculated as the time from the date of first study drug administration until death from any cause. Subjects alive at the time of analysis were censored at the time they were last known alive. OS was analyzed for the ITT population.
Time frame: Up to 2 years.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| NKTR-102 14 Day | Kaplan Meier Estimate of Overall Survival (OS) | 8.8 Months |
| NKTR-102 21 Days | Kaplan Meier Estimate of Overall Survival (OS) | 13.1 Months |
Secondary
Kaplan Meier Estimate of Progression-Free Survival (PFS)
Progression was defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions, or similar definition as accurate and appropriate.
Time frame: Up to 2 years.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| NKTR-102 14 Day | Kaplan Meier Estimate of Progression-Free Survival (PFS) | 3.3 Months |
| NKTR-102 21 Days | Kaplan Meier Estimate of Progression-Free Survival (PFS) | 5.6 Months |
Secondary
Percent of Patients With Treatment-Emergent Adverse Events (TEAE): NCI-CTCAE Grade 3 or Higher With Incidence Rate ≥ 2% in Either Treatment Group
An adverse event (AE) was defined as any untoward medical occurrence associated with the use of a drug in humans, whether or not considered drug related. An AE could therefore have been any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of an investigational product, whether or not thought to be related to the investigational product. TEAE was any event not present before exposure to the study drug or any event already present that worsened in either intensity or frequency after exposure to the study drug. All AEs were assessed for severity using the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) Version 3.0. If a particular AE was not listed in the NCI CTCAE Version 3.0, the following criteria were used: Grade 1 = Mild; Grade 2 = Moderate; Grade 3 = Severe; Grade 4 = Life threatening or disabling; Grade 5 = Death.
Time frame: Up to 2 years.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| NKTR-102 14 Day | Percent of Patients With Treatment-Emergent Adverse Events (TEAE): NCI-CTCAE Grade 3 or Higher With Incidence Rate ≥ 2% in Either Treatment Group | Fatigue | 14.3 percentage of subjects |
| NKTR-102 14 Day | Percent of Patients With Treatment-Emergent Adverse Events (TEAE): NCI-CTCAE Grade 3 or Higher With Incidence Rate ≥ 2% in Either Treatment Group | Dehydration | 8.6 percentage of subjects |
| NKTR-102 14 Day | Percent of Patients With Treatment-Emergent Adverse Events (TEAE): NCI-CTCAE Grade 3 or Higher With Incidence Rate ≥ 2% in Either Treatment Group | Percentage of Patient with at Least 1 TEAE | 68.6 percentage of subjects |
| NKTR-102 14 Day | Percent of Patients With Treatment-Emergent Adverse Events (TEAE): NCI-CTCAE Grade 3 or Higher With Incidence Rate ≥ 2% in Either Treatment Group | Neutropenia | 11.4 percentage of subjects |
| NKTR-102 14 Day | Percent of Patients With Treatment-Emergent Adverse Events (TEAE): NCI-CTCAE Grade 3 or Higher With Incidence Rate ≥ 2% in Either Treatment Group | Vomiting | 8.6 percentage of subjects |
| NKTR-102 14 Day | Percent of Patients With Treatment-Emergent Adverse Events (TEAE): NCI-CTCAE Grade 3 or Higher With Incidence Rate ≥ 2% in Either Treatment Group | Anaemia | 2.9 percentage of subjects |
| NKTR-102 14 Day | Percent of Patients With Treatment-Emergent Adverse Events (TEAE): NCI-CTCAE Grade 3 or Higher With Incidence Rate ≥ 2% in Either Treatment Group | Nausea | 5.7 percentage of subjects |
| NKTR-102 14 Day | Percent of Patients With Treatment-Emergent Adverse Events (TEAE): NCI-CTCAE Grade 3 or Higher With Incidence Rate ≥ 2% in Either Treatment Group | Dyspnoea | 2.9 percentage of subjects |
| NKTR-102 14 Day | Percent of Patients With Treatment-Emergent Adverse Events (TEAE): NCI-CTCAE Grade 3 or Higher With Incidence Rate ≥ 2% in Either Treatment Group | Decreased appetite | 2.9 percentage of subjects |
| NKTR-102 14 Day | Percent of Patients With Treatment-Emergent Adverse Events (TEAE): NCI-CTCAE Grade 3 or Higher With Incidence Rate ≥ 2% in Either Treatment Group | Disease progression | 14.3 percentage of subjects |
| NKTR-102 14 Day | Percent of Patients With Treatment-Emergent Adverse Events (TEAE): NCI-CTCAE Grade 3 or Higher With Incidence Rate ≥ 2% in Either Treatment Group | Lethargy | 2.9 percentage of subjects |
| NKTR-102 14 Day | Percent of Patients With Treatment-Emergent Adverse Events (TEAE): NCI-CTCAE Grade 3 or Higher With Incidence Rate ≥ 2% in Either Treatment Group | Diarrhoea | 20.0 percentage of subjects |
| NKTR-102 14 Day | Percent of Patients With Treatment-Emergent Adverse Events (TEAE): NCI-CTCAE Grade 3 or Higher With Incidence Rate ≥ 2% in Either Treatment Group | Dizziness | 2.9 percentage of subjects |
| NKTR-102 14 Day | Percent of Patients With Treatment-Emergent Adverse Events (TEAE): NCI-CTCAE Grade 3 or Higher With Incidence Rate ≥ 2% in Either Treatment Group | Abdominal pain | 2.9 percentage of subjects |
| NKTR-102 21 Days | Percent of Patients With Treatment-Emergent Adverse Events (TEAE): NCI-CTCAE Grade 3 or Higher With Incidence Rate ≥ 2% in Either Treatment Group | Dizziness | 2.9 percentage of subjects |
| NKTR-102 21 Days | Percent of Patients With Treatment-Emergent Adverse Events (TEAE): NCI-CTCAE Grade 3 or Higher With Incidence Rate ≥ 2% in Either Treatment Group | Percentage of Patient with at Least 1 TEAE | 54.3 percentage of subjects |
| NKTR-102 21 Days | Percent of Patients With Treatment-Emergent Adverse Events (TEAE): NCI-CTCAE Grade 3 or Higher With Incidence Rate ≥ 2% in Either Treatment Group | Diarrhoea | 22.9 percentage of subjects |
| NKTR-102 21 Days | Percent of Patients With Treatment-Emergent Adverse Events (TEAE): NCI-CTCAE Grade 3 or Higher With Incidence Rate ≥ 2% in Either Treatment Group | Nausea | 2.9 percentage of subjects |
| NKTR-102 21 Days | Percent of Patients With Treatment-Emergent Adverse Events (TEAE): NCI-CTCAE Grade 3 or Higher With Incidence Rate ≥ 2% in Either Treatment Group | Fatigue | 8.6 percentage of subjects |
| NKTR-102 21 Days | Percent of Patients With Treatment-Emergent Adverse Events (TEAE): NCI-CTCAE Grade 3 or Higher With Incidence Rate ≥ 2% in Either Treatment Group | Vomiting | 5.7 percentage of subjects |
| NKTR-102 21 Days | Percent of Patients With Treatment-Emergent Adverse Events (TEAE): NCI-CTCAE Grade 3 or Higher With Incidence Rate ≥ 2% in Either Treatment Group | Decreased appetite | 0 percentage of subjects |
| NKTR-102 21 Days | Percent of Patients With Treatment-Emergent Adverse Events (TEAE): NCI-CTCAE Grade 3 or Higher With Incidence Rate ≥ 2% in Either Treatment Group | Abdominal pain | 0 percentage of subjects |
| NKTR-102 21 Days | Percent of Patients With Treatment-Emergent Adverse Events (TEAE): NCI-CTCAE Grade 3 or Higher With Incidence Rate ≥ 2% in Either Treatment Group | Dehydration | 11.4 percentage of subjects |
| NKTR-102 21 Days | Percent of Patients With Treatment-Emergent Adverse Events (TEAE): NCI-CTCAE Grade 3 or Higher With Incidence Rate ≥ 2% in Either Treatment Group | Neutropenia | 11.4 percentage of subjects |
| NKTR-102 21 Days | Percent of Patients With Treatment-Emergent Adverse Events (TEAE): NCI-CTCAE Grade 3 or Higher With Incidence Rate ≥ 2% in Either Treatment Group | Anaemia | 2.9 percentage of subjects |
| NKTR-102 21 Days | Percent of Patients With Treatment-Emergent Adverse Events (TEAE): NCI-CTCAE Grade 3 or Higher With Incidence Rate ≥ 2% in Either Treatment Group | Dyspnoea | 0 percentage of subjects |
| NKTR-102 21 Days | Percent of Patients With Treatment-Emergent Adverse Events (TEAE): NCI-CTCAE Grade 3 or Higher With Incidence Rate ≥ 2% in Either Treatment Group | Lethargy | 0 percentage of subjects |
| NKTR-102 21 Days | Percent of Patients With Treatment-Emergent Adverse Events (TEAE): NCI-CTCAE Grade 3 or Higher With Incidence Rate ≥ 2% in Either Treatment Group | Disease progression | 8.6 percentage of subjects |