dm+d

Unassigned

New Medicines

OnzealdBreast cancer, metastatic - second- or third-line in patients with a history of brain metastases

Information

Onzeald
New formulation
Nektar Therapeutics
Nektar Therapeutics

Development and Regulatory status

Discontinued
Discontinued
Discontinued
Yes
Yes
Jun 21Development discontinued [20].
Mar 20No longer listed in company pipeline; development plans unclear [19].
Mar 18PIII development is continuing [14].
Feb 18Daiichi Sankyo Europe terminates their collaboration and license agreement with Nektar Therapeutics; all rights and licenses revert exclusively to Nektar [16].
Nov 17The company requested a re-examination of the initial opinion. After considering the grounds for this request, the CHMP re-examined the opinion, and confirmed the refusal of the marketing authorisation [13].
Jul 17EU negative opinion for etirinotecan pegol for advanced breast cancer which has spread to the brain. The CHMP considered that the benefit had not been sufficiently demonstrated. The claim of effectiveness relied on data from a subgroup of patients from a main study which, overall, failed to convincingly show effectiveness [12].
Jun 16Nektar Therapeutics enters into an agreement with Daiichi Sankyo Europe for the marketing rights of etirinotecan pegol. According to the agreement terms, Daiichi Sankyo Europe gains exclusive marketing rights for etirinotecan pegol in Europe, Switzerland and Turkey [11].
Jun 16To be filed this month in EU for conditional approval in treatment of advanced breast cancer and brain metastases [10].
Dec 15Remains in PIII development [9].
Mar 15Nektar Therapeutics announces top-line results from the PIII BEACON study. The trial did not meet statistical significance and the company is planning to explore potential paths with regulatory agencies for development of etirinotecan pegol for metastatic breast cancer [8].
Mar 14Granted Fast Track designation in US in Nov 2012 [5].
Jan 14The Independent Data Monitoring Committee (DMC) has recommended continuation of the BEACON PIII trial, based upon the completion of a planned interim efficacy analysis including 50% of patient events necessary to evaluate the primary endpoint of overall survival. Final results from the study are expected at the end of 2014 or early 2015, and if positive, the company will submit filings in the US and EU in 2H 2015 [4].

Category

Topoisomerase I inhibitor-polymer conjugate
The incidence of BC in the UK is about 80 per 100,000 people. About 40% develop metastatic disease; 25% of these are HER2-positive which has a worse prognosis.
Breast cancer, metastatic - second- or third-line in patients with a history of brain metastases
Intravenous

Further information

Yes

Trial or other data

Sep 19PIII ATTAIN study (NCT02915744) is recruiting & continuing as planned [18].
Oct 18PIII ATTAIN study is recruiting; collection of primary outcome data is now due to complete Jul 20 [17].
Jan 18PIII ATTAIN study is still recruiting. Collection of primary outcome data (OS) is due to complete Aug 19 [15].
Nov 16PIII ATTAIN trial to assess the efficacy of etirinotecan pegol versus treatment of physician´s choice in 350 patients with metastatic breast cancer with stable brain metastases and previously treated with an anthracycline, a taxane and capecitabine in either the adjuvant or metastatic setting starts in the US (NCT02915744) [15].
Oct 15Results of PIII study (BEACON) published in The Lancet Online [7].
Mar 15Results for the BEACON study announced; improved survival in patients by a little over two months but missed its primary endpoint. NKTR-102 provided a 2.1 month improvement in median overall survival (OS) for 852 patients over TPC (12.4 months for patients receiving NKTR-102 compared to 10.3 months for patients receiving TPC). In the subgroup with a history of brain metastases, NKTR-102 showed a statistically significant improvement of 5.2 months in median OS. For those with brain metastases the 12-month survival was 44.4% in the NKTR-102 arm vs. 19.4% in the control arm. For liver cancer, a statistically significant improvement of 2.6 months in median OS. In patients with baseline liver metastases, 12-month survival was 46.9%in the NKTR-102 arm vs. 33.3% in the control arm. [6]
Jan 14Positive PII data for NKTR-102 were published in Lancet Oncology in Nov 13. Etirinotecan pegol achieved a confirmed objective response rate by RECIST of 29% and demonstrated a high clinical benefit rate (CR+PR+SD >6 months) of 37% (13/35) in the 14-day group and 49% (17/35) in the 21-day group. Six patients experienced 100% resolution of all target lesions, with two complete RECIST responses and four near-complete responses. Patients exhibited low rates of alopecia, neuropathy and neutropenia. Side effects were generally manageable; the most common Grade 3 toxicity was diarrhoea (17-23%) typically occurring after three months of therapy [4].
Aug 13Enrollment in the BEACON study is complete. Investigators plan to conduct an interim futility analysis in Q1 2014 with top line survival data available at the end of 2014 [3].
Dec 11NCT01492101 the PIII BEACON open-label, randomized, multicentre study of NKTR-102 vs treatment of physician´s choice (TPC) in 840 patients with locally recurrent or metastatic breast cancer previously treated with an anthracycline, a taxane and capecitabine will start this month.
Sep 11PIII BEACON (BrEAst Cancer Outcomes with NKTR-102) study design announced. The BEACON study will enroll ~840 metastatic breast cancer pts who have had prior treatment with anthracycline, taxane and capecitabine (either adjuvant or metastatic). Patients will be randomised on a 1:1 basis to receive single-agent peg-irinotecan once every 3 weeks or a single agent of physician´s choice. The primary endpoint of the study will be overall survival, and secondary endpoints will include progression-free survival and objective tumor response rates. [2]
Sep 11Results from SIMON study presented at ASCO 2011. Peg-irinotecan achieved a confirmed objective response rate by RECIST of 29%. 71% had no tumour progression, defined as complete response (CR), partial response (PR) and stable disease (SD), as measured by RECIST criteria and a high clinical benefit (CR+PR+SD greater than six months) rate of 46% (30 of 66) was seen. Six patients experienced 100% resolution of all target lesions, with two complete RECIST responses and four near-complete responses. Objective tumour responses were maintained in heavily pretreated and poor prognosis subsets, including patients previously treated with anthracycline/taxane/capecitabine, patients with metastatic triple-negative breast cancer and patients with visceral disease. Pts experienced minimal alopecia, neuropathy and neutropenia and the most common Grade 3 toxicity was diarrhoea (17-23%) typically occurring after three months of therapy for both schedules. [2]
Dec 10PII data from SIMON 2-stage study in 70 pts with metastatic breast cancer. Pts had been previously treated with an anthracycline/taxane with or without capecitabine. Primary endpoint = objective tumour response rate (ORR): ORR for all 66 evaluable pts was 32% (10/31) for peg-irinotecan 145 mg/m2 every 2 weeks and 26% (9/35) for 145 mg/m2 every 3 weeks. Two confirmed complete responses in 2 week schedule. Additional 4 pts had near CRs with 100% disappearance of all target lesions. The combined ORR for all evaluable patients was 29% (19/66). [1]

Evidence based evaluations