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

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

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.

Study Overview

• Status: Completed
• Conditions: Metastatic Breast Cancer; Locally Recurrent Breast Cancer
• Intervention / Treatment: Drug: NKTR-102; Drug: Treatment of Physician's Choice (TPC)

• Study Type: Interventional
• Enrollment (Actual): 852
• Phase: Phase 3

Contacts and Locations

Study Locations

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

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Kaplan-Meier Estimate of Overall Survival: Intention to Treat (ITT) Population	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.	36 Months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Kaplan-Meier Estimate of Progression-Free Survival (PFS): ITT Population	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.	Up to 38 months.
Clinical Benefit Rate (CBR): ITT Population	CBR was defined as the proportion of subjects with a CR, PR, or stable disease (SD) for at least 6 months (≥ 182 days).	Up to 38 months.
Duration of Response (DOR): Efficacy Evaluable Population	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.	Up to 38 months.
Incidence of Dose Reductions: Safety Population	Proportion of subjects who had a reduction in dose.	Up to 38 months.
Quality of Life Questionnaire-Core 30 (QLQ-C30) Individual Scale, Overall Score: ITT Population	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.	Up to 39 months
QLQ-C30 Individual Scale, Change Over Time: ITT Population	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.	From Baseline to Week 8, Week 16, Week 24, Week 32, Week 40, Week 48, Week 56.
Quality of Life Questionnaire-breast Cancer-specific Module (BR23) Score Value: ITT Population	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.	Baseline
BR23 Score Change Over Time: ITT Population	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.	Up to 38 months.
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]	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.	Up to 38 months.
Population Mean ± SD Maximum Plasma Concentration (Cmax) for NKTR-102 and Metabolites After Multiple Administration of 145 mg/m^2 NKTR-102 [26]	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.	Up to 38 months.
Population Mean ± SD Elimination Half-life (t½) for NKTR-102 After Multiple Administration of 145 mg/m^2 NKTR-102 [27]	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.	Up to 38 months.
Objective Response Rate (ORR): Efficacy Evaluable Population	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.	Up to 38 months.

Collaborators and Investigators

• Sponsor: Nektar Therapeutics

Publications and helpful links

General Publications

• Park EJ, Choi J, Lee KC, Na DH. Emerging PEGylated non-biologic drugs. Expert Opin Emerg Drugs. 2019 Jun;24(2):107-119. doi: 10.1080/14728214.2019.1604684. Epub 2019 Apr 19.
• Cortes J, Rugo HS, Awada A, Twelves C, Perez EA, Im SA, Gomez-Pardo P, Schwartzberg LS, Dieras V, Yardley DA, Potter DA, Mailliez A, Moreno-Aspitia A, Ahn JS, Zhao C, Hoch U, Tagliaferri M, Hannah AL, O'Shaughnessy J. Prolonged survival in patients with breast cancer and a history of brain metastases: results of a preplanned subgroup analysis from the randomized phase III BEACON trial. Breast Cancer Res Treat. 2017 Sep;165(2):329-341. doi: 10.1007/s10549-017-4304-7. Epub 2017 Jun 13. Erratum In: Breast Cancer Res Treat. 2017 Nov;166(1):327-328.
• Twelves C, Cortes J, O'Shaughnessy J, Awada A, Perez EA, Im SA, Gomez-Pardo P, Schwartzberg LS, Dieras V, Yardley DA, Potter DA, Mailliez A, Moreno-Aspitia A, Ahn JS, Zhao C, Hoch U, Tagliaferri M, Hannah AL, Rugo HS. Health-related quality of life in patients with locally recurrent or metastatic breast cancer treated with etirinotecan pegol versus treatment of physician's choice: Results from the randomised phase III BEACON trial. Eur J Cancer. 2017 May;76:205-215. doi: 10.1016/j.ejca.2017.02.011. Epub 2017 Mar 27.
• Perez EA, Awada A, O'Shaughnessy J, Rugo HS, Twelves C, Im SA, Gomez-Pardo P, Schwartzberg LS, Dieras V, Yardley DA, Potter DA, Mailliez A, Moreno-Aspitia A, Ahn JS, Zhao C, Hoch U, Tagliaferri M, Hannah AL, Cortes J. Etirinotecan pegol (NKTR-102) versus treatment of physician's choice in women with advanced breast cancer previously treated with an anthracycline, a taxane, and capecitabine (BEACON): a randomised, open-label, multicentre, phase 3 trial. Lancet Oncol. 2015 Nov;16(15):1556-1568. doi: 10.1016/S1470-2045(15)00332-0. Epub 2015 Oct 22.

Study record dates

Study Major Dates

• Study Start: December 1, 2011
• Primary Completion (ACTUAL): April 1, 2016
• Study Completion (ACTUAL): June 1, 2016

Study Registration Dates

• First Submitted: December 12, 2011
• First Submitted That Met QC Criteria: December 12, 2011
• First Posted (ESTIMATE): December 14, 2011

Study Record Updates

• Last Update Posted (ACTUAL): June 1, 2021
• Last Update Submitted That Met QC Criteria: May 6, 2021
• Last Verified: May 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Breast Neoplasms; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Topoisomerase II Inhibitors; Topoisomerase Inhibitors; Etirinotecan pegol
• Other Study ID Numbers: 11-PIR-11