SIGNIFICANT ANTITUMOR ACTIVITY IN A RANDOMIZED PHASE 2 STUDY COMPARING 2 SCHEDULES OF NKTR-102 IN PATIENTS (PTS) WITH METASTATIC BREAST CANCER (MBC)

ABSTRACT Background NKTR-102 is a topoisomerase I inhibitor-polymer conjugate with reduced peak concentration and a continuous concentration profile. Methods This was an open-label phase 2 study in pts with advanced MBC; pts were randomized to NKTR-102 given IV at a dose of 145 mg/m2 over 90-min every 14 or 21 days. The primary endpoint was objective response rate (ORR) by RECIST v1.0; secondary endpoints were safety and PFS. Each schedule followed a 2-stage Simon design (≥1 response in 15 pts was required to enroll an additional 20 pts per schedule). Results 70 pts (35 per schedule) were randomized from Feb09 - Apr10. Median age: 55 (range 37-83). ECOG PS 0/1: 40%/60%. Median number of prior cytotoxic regimens for metastatic disease (not including hormonal therapy or biologics) was 2. All pts had received prior taxane (T). 89% had received prior anthracyclines (A). 26% had received prior AT/capecitabine (ATC). 61% were ER/PR + ; 30% had TNBC; 86% had visceral metastases. Table 1 . q14d q21d Total ORR (n = 31*/35) 32% 26% 29% CR 7% 0 3% PR 26% 26% 26% CR + PR + SD ≥ 6 months 42% 49% 46% ORR: AT (n = 22/21) 32% 24% 28% ORR: ATC (n = 6/10) 33% 30% 31% ORR: TNBC (n = 8/10) 25% 50% 39% ORR: visceral disease (n = 25/32) 32% 28% 30% mPFS (mon; n = 70) 3.5 5.3 4.6 mOS (mon; n = 70) 8.8 13.1 10.3 *4 pts (q14d) without on-study scans: excluded from the evaluable population. Common related Grade 3/4 toxicity (q14d/q21d; n = 70): diarrhea (20%/23%, median time to onset ∼3 mon), neutropenia (11%/11%), fatigue (11%/9%) and dehydration (9%/11%). Withdrawal due to AEs equaled 20% and 14% by schedule. Neuropathy was absent; alopecia was minimal ( Conclusions NKTR-102 demonstrates significant anti-tumor activity in pts with advanced MBC, including pts with TNBC, visceral disease or prior ATC therapy. Toxicity was manageable. An international phase 3 clinical trial comparing single-agent NKTR-102 to Treatment of Physicianu0027s Choice is underway. Disclosure A. Awada: Dr Awada is an advisory board member of Nektar Therapeutics All other authors have declared no conflicts of interest.