Phase I study of imetelstat (GRN163L) in combination with paclitaxel (P) and bevacizumab (B) in patients (pts) with locally recurrent or metastatic breast cancer (MBC).

2598 Background: Following debulking chemotherapy, tumor regrowth may rely on proliferation of a cellular subcompartment with progenitor cell or “stem cell”-like properties. Self-renewal of this stem cell compartment requires the presence of telomerase, making inhibition of telomerase an appealing therapeutic strategy. Imetelstat, the first targeted telomerase inhibitor in clinical trials, is a 13-mer lipidated oligonucleotide that binds to the template RNA strand of telomerase. Methods: Pts with locally recurrent or MBC were treated with imetelstat in addition to P+B as in the previous E2100 study. Pts with prior adjuvant taxane therapy within 12 months were excluded. In a standard 3+3 dose-escalation design, imetelstat (160-375 mg/m2 2-hr IV infusion) was administered on days 1, 8, and 15 of a 28-day cycle. Study objectives were to define the maximally tolerated dose (MTD) and obtain preliminary safety and efficacy. Dose-limiting toxicities were determined by presence of hematologic toxicities and recei...