Study to Evaluate the Safety and Efficacy of NKTR-102 in Patients With Metastatic or Locally Advanced Breast Cancer

Study Overview
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Brief Summary
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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.

Official Title
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A Multicenter, Open-Label, Phase 2 Study to Evaluate the Safety and Efficacy of NKTR-102 When Given on a Q14 Day or a Q21 Day Schedule in Patients With Metastatic or Locally Advanced Breast Cancer Whose Disease Has Failed Prior Taxane-Based Treatment

Conditions
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Tumor, Breast Cancer

Intervention / Treatment
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* Drug: NKTR-102
* Drug: NKTR-102


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Inoperable metastatic or locally advanced breast cancer 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: Patients who have had chemotherapy or radiotherapy within 4 weeks (6 weeks for nitrosoureas or mitomycin C) prior to Day 1 of Cycle 1 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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: NKTR-102 q14d<br>NKTR-102 | Drug: NKTR-102<br>* NKTR-102 given on a q14 day schedule<br>|
| Experimental: NKTR-102 q21d<br>NKTR-102 | Drug: NKTR-102<br>* NKTR-102 given on a q21 day schedule<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | Up to 2 years. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | Up to 2 years. | 
| 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. | Up to 2 years. | 
| 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. | From Cycle 1 Day 1 to the end of 6 months. | 
| 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. | From Cycle 1 Day 1 to the end of 12 months. | 
| 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. | Up to 2 years. |