Neoplasms

Skin and Connective Tissue Diseases

All Conditions

Symptoms and General Pathology

Breast Neoplasms

Recurrence

Breast Diseases

Skin Diseases

Antineoplastic Agents

All Drugs and Chemicals

Paclitaxel

Gemcitabine

Capecitabine

Vinorelbine

Docetaxel

Albumin-Bound Paclitaxel

Taxane

Etirinotecan pegol

Enzyme Inhibitors

145 mg/m2 NKTR-102 will be delivered q21day as a 90-minute intravenous (IV) infusion on day 1 of each treatment cycle.

NKTR-102

One of the following Treatment of Physician Choice will be administered per standard of care:

eribulin, ixabepilone, vinorelbine, gemcitabine, paclitaxel, docetaxel, or nab-paclitaxel

Treatment of Physician's Choice (TPC)

Alison Hannah, MD

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.

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

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

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.

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.

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

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.

Proportion of subjects who had a reduction in dose.

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.

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.

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.

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.

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.

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.

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.

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.

Nektar Therapeutics

Safety Population NKTR-102 = 425; TPC = 406

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

Physician's Treatment of Choice

Total

Age, Categorical

Age, Continuous

Sex: Female, Male

Canada

South Korea

Netherlands

Belgium

United States

Italy

United Kingdom

France

Germany

Spain

Russia

Region of Enrollment

Kaplan-Meier Estimate of Overall Survival: Intention to Treat (ITT) Population

Kaplan-Meier Estimate of Progression-Free Survival (PFS): ITT Population

Clinical Benefit Rate (CBR): ITT Population

The population analyzed for this outcome measure solely comprised of patients who achieved CR or PR per RECIST.

Duration of Response (DOR): Efficacy Evaluable Population

Incidence of Dose Reductions: Safety Population

Global health status/QoL

Physical functioning

Role functioning

Emotional functioning

Cognitive functioning

Social functioning

Fatigue

Nausea and vomiting

Pain

Dyspnoea

Insomnia

Appetite loss

Constipation

Diarrhoea

Financial difficulties

429 (ITT Population) 423 (ITT Population)

Quality of Life Questionnaire-Core 30 (QLQ-C30) Individual Scale, Overall Score: ITT Population

Global health status/QoL: change from baseline to last assessment (Week 56)

Global health status/QoL: Week 8

Global health status/QoL: Week 16

Global health status/QoL: Week 24

Global health status/QoL: Week 32

Global health status/QoL: Week 40

Global health status/QoL: Week 48

Global health status/QoL: Week 56

Physical functioning: Week 8

Physical functioning: Week 16

Physical functioning: Week 24

Physical functioning: Week 32

Physical functioning: Week 40

Physical functioning: Week 48

Physical functioning: Week 56

Role functioning: Week 8

Role functioning: Week 16

Role functioning: Week 24

Role functioning: Week 32

Role functioning: Week 40

Role functioning: Week 48

Role functioning: Week 56

Emotional functioning: Week 8

Emotional functioning: Week 16

Emotional functioning: Week 24

Emotional functioning: Week 32

Emotional functioning: Week 40

Emotional functioning: Week 48

Emotional functioning: Week 56

Cognitive functioning: Week 8

Cognitive functioning: Week 16

Cognitive functioning: Week 24

Cognitive functioning: Week 32

Cognitive functioning: Week 40

Cognitive functioning: Week 48

Cognitive functioning: Week 56

Social functioning: Week 8

Social functioning: Week 16

Social functioning: Week 24

Social functioning: Week 32

Social functioning: Week 40

Social functioning: Week 48

Social functioning: Week 56

Fatigue: Week 8

Fatigue: Week 16

Fatigue: Week 24

Fatigue: Week 32

Fatigue: Week 40

Fatigue: Week 48

Fatigue: Week 56

Nausea and vomiting: Week 8

Nausea and vomiting: Week 16

Nausea and vomiting: Week 24

Nausea and vomiting: Week 32

Nausea and vomiting: Week 40

Nausea and vomiting: Week 48

Nausea and vomiting: Week 56

Pain: Week 8

Pain: Week 16

Pain: Week 24

Pain: Week 32

Pain: Week 40

Pain: Week 48

Pain: Week 56

Dyspnoea: Week 8

Dyspnoea: Week 16

Dyspnoea: Week 24

Dyspnoea: Week 32

Dyspnoea: Week 40

Dyspnoea: Week 48

Dyspnoea: Week 56

Insomnia: Week 8

Insomnia: Week 16

Insomnia: Week 24

Insomnia: Week 32

Insomnia: Week 40

Insomnia: Week 48

Insomnia: Week 56

Appetite loss: Week 8

Appetite loss: Week 16

Appetite loss: Week 24

Appetite loss: Week 32

Appetite loss: Week 40

Appetite loss: Week 48

Appetite loss: Week 56

Constipation: Week 8

Constipation: Week 16

Constipation: Week 24

Constipation: Week 32

Constipation: Week 40

Constipation: Week 48

Constipation: Week 56

Diarrhoea: Week 8

Diarrhoea: Week 16

Diarrhoea: Week 24

Diarrhoea: Week 32

Diarrhoea: Week 40

Diarrhoea: Week 48

Diarrhoea: Week 56

Financial difficulties: Week 8

Financial difficulties: Week 16

QLQ-C30 Individual Scale, Change Over Time: ITT Population

Body image

Sexual functioning

Sexual enjoyment

Future perspective

Systemic therapy side effects

Breast symptoms

Arm symptoms

Upset by hair loss

Quality of Life Questionnaire-breast Cancer-specific Module (BR23) Score Value: ITT Population

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
The BEACON Study (Breast Cancer Outcomes With NKTR-102)	NCT01492101	Locally Recurre... Metastatic Brea...	NKTR-102 Treatment of Ph...	18 Years -	Nektar Therapeutics
The BEACON Study (Breast Cancer Outcomes With NKTR-102)	NCT01492101	Locally Recurre... Metastatic Brea...	NKTR-102 Treatment of Ph...	18 Years -	Nektar Therapeutics
The BEACON Study (Breast Cancer Outcomes With NKTR-102)	NCT01492101	Locally Recurre... Metastatic Brea...	NKTR-102 Treatment of Ph...	18 Years -	Nektar Therapeutics

Spots Global Cancer Trial Database for treatment of physician's choice (tpc)