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

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.

• Locally Recurrent Breast Cancer
• Metastatic Breast Cancer

• 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.
• 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

• Experimental: NKTR-102
  Intervention: Drug: NKTR-102
• Active Comparator: Physician's Treatment of Choice
  Intervention: Drug: Treatment of Physician's Choice (TPC)

• Cortés J, Rugo HS, Awada A, Twelves C, Perez EA, Im SA, Gómez-Pardo P, Schwartzberg LS, Diéras 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 Sep 7;:.
• Perez EA, Awada A, O'Shaughnessy J, Rugo HS, Twelves C, Im SA, Gómez-Pardo P, Schwartzberg LS, Diéras 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):1556-68. doi: 10.1016/S1470-2045(15)00332-0. Epub 2015 Oct 22.

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.