CHICAGO and SAN FRANCISCO, June 4, 2011 /PRNewswire/ -- Nektar Therapeutics (Nasdaq: NKTR) today announced positive results from a Phase 2 clinical study evaluating single-agent NKTR-102 as a second- and third-line treatment in patients with metastatic breast cancer during the 2011 American Society of Clinical Oncology Meeting (ASCO). NKTR-102, a next-generation topoisomerase I inhibitor, is Nektar's lead oncology drug candidate and is being evaluated in multiple cancer indications. The randomized Simon two-stage study presented at ASCO evaluated two 145 mg/m2 dose schedules of single-agent NKTR-102, every two weeks (q14d) and every three weeks (q21d), in 70 metastatic breast cancer patients who failed a prior taxane therapy. Eighty-nine percent (62/70) of patients in the study received a prior anthracycline/taxane with or without capecitabine.
More than one million women worldwide are diagnosed with breast cancer every year and the disease is the leading cause of cancer-related death among women.(1)
A total of 66 of the 70 patients treated with single-agent NKTR-102 in the Phase 2 study were assessable for the primary endpoint of objective tumor response rate (ORR), including confirmed complete responses (CRs) and partial responses (PRs) per RECIST 1.0. As of May 9, 2011, for the q14d day schedule, the confirmed and unconfirmed ORR was 35 percent (11/31) and the confirmed ORR was 32 percent (10/31), including two confirmed CRs. Clinical benefit rate for the 31 evaluable patients in the q14d schedule was 42% (13/31) (defined as confirmed CR+ PR+ Stable Disease (SD) >6 mos). For the q21d schedule, the confirmed and unconfirmed ORR was 31 percent (11/35) and the confirmed ORR was 26 percent (9/35). Clinical benefit rate for the 35 evaluable patients in the q21d schedule was 49% (17/35). Clinical benefit rate for the overall study population was 46%. An additional four patients in the study had near CRs, with 100% disappearance of all target lesions.
"NKTR-102 is emerging as a promising anti-cancer investigational treatment with the potential to become the first topoisomerase I-inhibitor to be used in the fight against breast cancer," said Prof. Ahmad Awada, Head of the Medical Oncology Clinic at the Institut Jules Bordet in Brussels, Belgium. "The drug's high confirmed objective response rate and clinical benefit is very interesting, particularly when one observes that this response rate was maintained in patients pre-treated with anthracyclines, taxanes with or without capecitabine, and also maintained in poor prognosis subsets within the study, such as triple-negative breast cancer and patients with visceral disease."
The confirmed ORR in patients previously treated with anthracycline/taxane/capecitabine was 31% (5/16); confirmed ORR in patients with metastatic triple-negative breast cancer was 39% (7/18); and confirmed ORR in patients with visceral disease was 30% (17/57).
"The every three week dose schedule appears well-tolerated overall and demonstrates encouraging PFS and OS of 5.3 months and 13.1 months, respectively," continued Dr. Awada. "We are in need of effective new therapeutic options whose mechanism of action is different from those already available for women with metastatic breast cancer and we look forward to NKTR-102 entering Phase 3 development."
Patients treated in the single-agent NKTR-102 study had a median of two lines of prior cytotoxic treatments for metastatic disease. Seventy-four percent (52/70) of the patients received neoadjuvant and/or adjuvant therapy and 86% (60/70) had visceral disease.
"The clinical benefit we've observed in multiple tumor settings with NKTR-102, where a highly active topoisomerase 1 inhibitor could be extremely useful, makes us very excited about the future of this new anticancer drug candidate," said Lorianne Masuoka, M.D., Senior Vice President and Chief Medical Officer.
Side effects were generally manageable with dose-limiting toxicity consisting primarily of Grade 3 diarrhea (20-23%) typically occurring after three months of therapy for both schedules. Neuropathy and alopecia were minimal with only one patient experiencing G2 alopecia in the study. Both neuropathy and alopecia are significant adverse events commonly associated with standard breast cancer therapies [Safety Tables, Figures D and E].
NKTR-102 Phase 2 Data Presentation in Metastatic Breast Cancer
Awada et. al., Antitumor activity in a randomized phase II study comparing two schedules of NKTR-102 in patients (Pts) with pretreated metastatic breast cancer (MBC).
Abstract #1034, Poster Board #24
Poster Discussion Session: Breast Cancer - Triple-negative/Cytotoxics/Local Therapy
Session Date and Time: Saturday, June 4, 2011, 2:00 PM 6:00 PM, Central Time
Figure A: Efficacy Table: Objective Tumor Response Rate by RECIST (Investigator Assessment)
Response by RECIST v 1.0
ORR (confirmed + unconfirmed)
Median duration of response
Median progression-free survival**
Median overall survival**
*4 patients in the Q14 day arm with no post-baseline scans, but no evidence of progression were excluded from analysis in the evaluable population.
**based on a Kaplan-Meier analysis for the intent-to-treat population.
Figure B: Efficacy Table: Response rate by prior therapy
Prior Therapy Subgroup
Response by RECIST v 1.0
Prior A/T only
Prior A/T in MBC
Figure C: Efficacy Table: Response rate by tumor characteristics
Response by RECIST v 1.0