Abstract OT3-01-13: MetaPHER: A phase IIIb multicenter, open-label, single-arm safety study of subcutaneous trastuzumab, in combination with pertuzumab and docetaxel in patients with HER2-positive advanced breast cancer
Authors: S Kümmel, A Crepelle-Fléchais, M Schlegel, C Hillenbach, A Swat, M Franz, P Girase, A Schneider, D Heinzmann, M Shing
Journal: Cancer Research (2016)

Abstract Background: In patients (pts) with HER2-positive metastatic breast cancer (BC), the phase III CLEOPATRA study (NCT00567190) demonstrated significant improvement in progression-free (PFS) and overall survival (OS) from first-line treatment with intravenous (IV) pertuzumab (PERJETA® [P IV]) plus trastuzumab (Herceptin® [H IV]) plus docetaxel (D IV). HannaH (NCT00950300), a phase III trial in pts with HER2-positive early BC demonstrated that fixed-dose trastuzumab subcutaneous (Herceptin® [H SC]) is non-inferior to weight-based H IV infusion in the co-primary endpoints of serum trough concentration and pathologic complete response, which was supported by the long-term efficacy endpoints of event-free survival (EFS) and OS. The safety profile of H SC was consistent with the known safety profile of H IV. H SC is comprised of 600 mg trastuzumab and recombinant human hyaluronidase (rHuPH20) as an excipient, allowing a significantly reduced administration time compared with H IV (5 mins versus 30–90 mins, respectively). The MetaPHER study is designed to investigate the safety and efficacy of H SC in combination with P IV and D IV in pts with HER2-positive advanced BC. Trial design: MetaPHER is a phase IIIb multicenter, open-label, single-arm study, with eligible pts receiving H SC 600 mg/5 mL q3w, P IV (840 mg loading dose, then 420 mg at each subsequent cycle q3w), and D IV (at least 6 cycles at 75 mg/m2 q3w with possible escalation to 100 mg/m2 q3w; after Cycle 6, continuation of docetaxel is at the investigator's discretion). Study treatment is administered until disease progression, unacceptable toxicity, withdrawal of consent, death, or predefined study end, whichever occurs first. Pts will receive post-treatment follow-up for safety and survival. Eligibility: Women aged ≥18 years with metastatic or locally recurrent HER2-positive BC, ECOG performance status 0 or 1, and a left ventricular ejection fraction ≥50% are eligible. Exclusion criteria include disease-free interval of &amp;lt;6 months from completion of adjuvant or neoadjuvant non-hormonal treatment to disease recurrence; previous systemic non-hormonal therapy for metastatic or locally recurrent BC; history of persistent grade ≥2 hematological toxicity; current grade ≥3 peripheral neuropathy; or clinically significant cardiovascular disease. Aims: The primary objective is to evaluate the safety and tolerability of H SC in combination with P IV and D IV in pts with HER2-positive advanced BC. Secondary endpoints include PFS, OS, objective response rate and incidence of anti-trastuzumab and anti-rHuPH20 antibody formation. Statistical methods: Safety and efficacy results will be summarized descriptively to include all enrolled pts who received at least one dose of any study drug; the study is not designed for formal hypothesis testing. A sample size of 400 pts provides reasonable precision for the estimation of grade ≥3 AEs and cardiac AEs. Accrual: MetaPHER is enrolling, FPI was May 2015, and target enrollment is 400 pts; clinicaltrials.gov ID: NCT02402712. Contact information: For more information or to refer a patient, email global.rochegenentechtrials@roche.com or call 1-888-662-6728 (USA only). Citation Format: Kümmel S, Crepelle-Fléchais A, Schlegel M, Hillenbach C, Swat A, Franz M, Girase P, Schneider A, Heinzmann D, Shing M. MetaPHER: A phase IIIb multicenter, open-label, single-arm safety study of subcutaneous trastuzumab, in combination with pertuzumab and docetaxel in patients with HER2-positive advanced breast cancer. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr OT3-01-13.