Phase II study of DHP107 oral paclitaxel in first-line, HER2 negative recurrent/metastatic breast cancer (OPTIMAL study, NCT03315364)

Abstract

Background: DHP107 is a novel oral formulation composed of lipid based components and paclitaxel. DHP107 showed efficacy and safety comparable to IV paclitaxel in patients (pts) with AGC {Ann Oncol 2018}. DHP 107 was approved for marketing in 2016 for gastric cancer in Korea as first oral paclitaxel in the world. Another phase II clinical trial of DHP107 for PKs in breast cancer is ongoing in USA. Methods: This trial is conducted using Simon's optimal two stage design, and planned to proceed to stage 2, if ≥2 of 9 pts showed objective response in stage 1. DHP107 is considered adequately effective to proceed into phase III trial if ≥9 of 34 showed PR in stage 2. Subjects are eligible for the study regardless lines of endocrine therapy. Pts are administrated with DHP107 (200mg/m2 po bid D1, 8 & 15 q4wks) and response evaluation (RECIST v1.1) was done every 8wks (±1w). The primary tumor assessment was done by investigator's review (IR). Independent central review (ICR) was followed for sensitivity analysis. Primary endpoint is objective response rate (ORR) and secondary endpoints are progression free survival (PFS), overall survival (OS), disease control rate (DCR) and safety. Results: Total 36 subjects (including 11 TNBC pts) were enrolled during Dec 2017 until Oct 2018. Per Protocol set (PPS) was composed of 33 pts and 14 pts are still on treatment. Safety Analysis set (SAS) included 36 pts. ORR was 48.5% (CR 0%; PR 48.5%) by the IR vs 36.4% (CR 0%; PR 36.4%) by ICR. DCR was similar between the investigator's decision (90.9%) and ICR (84.9%). Most common adverse events (AEs) were neutropenia; Gr. 3/4 Neutropenia (75%), Anemia (16.7%) and Peripheral neuropathy (5.6%). There were 2 SAEs related to Gr. 3/4 neutropenia without fever. One patient discontinued due to Gr 3 peripheral neurotoxicity. There was no treatment-related toxic death. Conclusions: Based on confirmed PR (n=16/33, 48.5%), DHP107 demonstrated adequate efficacy with manageable toxicity in the first line HER2 negative recurrent/ metastatic breast cancer patients. Phase III trial in breast cancer is ongoing in Korea and China.