NKTR-102 Shows Promise in Phase II Trial

Ahmad Awada, MD, PhD

Metastatic breast cancer patients with demonstrated disease progression after taxane therapy face an uphill battle in fighting their disease. Results from a phase II trial of a topoisomerase I inhibitor-polymer conjugate, NKTR-102 (Nektar Therapeutics, San Francisco, California), offer hope of a new tool in the treatment of breast cancer as the compound demonstrated significant antitumor activity, including in patients with triple-negative breast cancer, visceral disease, or prior anthracycline/taxane/capecitabine therapy.

Ahmad Awada, MD, PhD, head of the New Drugs Development Unit at Jules Bordet Institute in Brussels, Belgium, and colleagues unveiled their research with NKTR-102 in a poster presentation on Saturday at the ASCO conference in Chicago. NKTR-102 is in phase II clinical development for patients with solid tumor malignancies, including colorectal, breast, and ovarian cancers. The compound’s pharmacokinetic profile provides a continuous concentration of active drug with reduced peak concentrations and leverages a releasable polymer technology platform.

The open-label phase II study consisted of 70 patients with metastatic breast cancer who had demonstrated disease progression on taxane. They ranged in age from 33 to 83 years, with a median age of 55. Two schedules were created, with 35 patients in each schedule.

The patients were randomized to NKTR-102 and received 145 mg/m2 intravenously over 90 minutes every 14 or 21 days. According to the researchers, the primary end point was overall response rate (ORR) by Response Evaluation Criteria In Solid Tumors (RECIST) v1.0; secondary end points were safety and progression-free survival (PFS). According to Awada and colleagues, each schedule followed a two-stage Simon design (≥1 response in 15 patients in order to enroll an additional 20 patients per schedule).

They reported that the Eastern Cooperative Oncology Group Performance Status of 0/1 for the 14-day and 21-day schedule was 40% and 60%, respectively. The median number of prior cytotoxic regimens for metastatic disease, not including hormonal therapy or biologics, was 2 (with a range of 0-4). All patients had received prior taxane: 10% (adjuvant) and 90% (metastatic).

In addition, 87% of the cohort had received prior anthracyclines: 59% (adjuvant) and 29% (metastatic). The researchers wrote that 64% had received prior anthracycline taxane and an additional 23% had received prior anthracycline taxane capecitabine. They noted that 61% were estrogen receptor/progesterone receptor positive (ER/PR+); 30% had triple negative breast cancer; and 87% had visceral metastases.

Four patients in the 14-day schedule were excluded from the evaluable population. The ORR was 32% for the 14-day schedule and 26% for the 21-day schedule, for a total ORR of 29%. The median time to response was 1.4 months for both schedules, and the duration of response was 8.3 months for the 14-day schedule and 4.4 months for the 21-day schedule. The mean PFS for the 14-day schedule was 3.3 months and 5.3 months for the 21-day schedule, with a mean PFS total for both schedules of 4.6 months. The researchers noted that neuropathy was absent and alopecia was minimal (1% grade 2).

Awada and colleagues reported that toxicity was manageable in this phase II study, and that a phase III clinical trial of NKTR-102 is planned, with the schedule to be selected on the basis of a full analysis of safety and activity data.

Awada A, Chan S, Jerusalem GHM, 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). J Clin Oncol. 29:2011(suppl; abstract 1034).