In a phase 2 study, eribulin (ERI) demonstrated single-agent activity in first-line treatment of pts with human epidermal growth factor receptor 2–negative (HER2–) MBC. Accumulation of hyaluronan (HA), a major component of the tumor stroma, is associated with accelerated tumor growth and metastasis. PEGylated recombinant human hyaluronidase (PEGPH20) degrades HA to reduce tumor interstitial fluid pressure and increase tumor perfusion. In high-HA triple-negative breast cancer (TNBC) xenografts, PEGPH20 increased the intratumoral accumulation of ERI, enhancing antitumor activity. This randomized study of ERI plus PEGPH20 aims to evaluate safety, tolerability, and efficacy in HER2− high-HA MBC.
This trial was activated in June 2016 and will enroll ~114 pts (n=6–18, phase 1b; n=12, phase 1b expansion; n=84, phase 2) with measurable disease (RECIST v1.1), ECOG PS 0–1, and prior treatment with ≤2 lines of systemic anticancer therapy. Phase 1b includes at least 1 safety run-in cohort in which 6 pts (any HA level) will receive PEGPH20 3 μg/kg IV on days −1 and 7 of a 21-d cycle, followed ~24 (±4) hours later with ERI 1.4 mg/m2 IV on days 1 and 8. Dose-limiting toxicity (DLT) will be assessed in the first cycle. The primary endpoint (phase 1b) is the recommended phase 2 dose (RP2D), defined as the maximum dose at which ≤1 pt experiences a DLT. If needed, modified dose levels will be evaluated in additional cohorts. Upon RP2D determination, phase 1b will enroll 12 additional pts.
In phase 2, high-HA pts will be stratified by TNBC vs other HER2− status and randomized to receive RP2D combination treatment or ERI alone. The primary endpoint in phase 2 is objective response rate. Secondary endpoints include progression-free survival and overall survival. Exploratory endpoints include clinical benefit rate, disease control rate, and duration of response.