Phase II study of DHP107 (oral paclitaxel) in the first-line treatment of HER2-negative recurrent or metastatic breast cancer (OPTIMAL study)

Abstract

Background: Standard intravenous (IV) paclitaxel is associated with hypersensitivity/toxicity. Alternative IV formulations have improved tolerability but still require frequent hospital visits and IV infusion. DHP107 is a novel oral formulation of paclitaxel that is approved in South Korea for the treatment of gastric cancer. Methods: This multicenter, phase II study using a Simon’s two-stage design investigated the efficacy and safety of DHP107 200 mg/m2 administered orally twice daily on days 1, 8, and 15 every 4 weeks for the first-line treatment of recurrent or metastatic HER2-negative breast cancer. Results: Thirty-six patients were enrolled and 31 were assessable for efficacy. Patient median age was 57 years (range = 34–81) and 11 (31%) had triple-negative disease. A median of seven cycles (range = 1–28) of DHP107 was administered. Objective response rate was 55% (17 patients), all partial responses, according to the investigator’s decision and independent central review (ICR), and 44% (4/9 patients) in those with triple-negative disease. Disease control rate (partial response and stable disease) was 74% (23 patients) according to the investigator’s decision and ICR. In the intention-to-treat (ITT) population of all enrolled participants, the objective response rate was 50% (18/36 patients). Median progression-free survival was 8.9 months [95% confidence interval [CI]: 5.2–12.3) and median time to treatment failure was 8.0 months (95% CI: 4.2–10.0). DHP107 had an acceptable toxicity profile. All patients experienced treatment-emergent adverse events; the most common adverse events were decreased neutrophil count (81% all grades and 78% grade ⩾ 3) followed by peripheral sensory neuropathy (61% all grades and 8% grade 3). However, there was no febrile neutropenia or sepsis. Conclusion: DHP107 showed promising efficacy and acceptable tolerability in this phase II study and is currently being investigated in the OPTIMAL phase III study (NCT03315364). Trial registration: This trial was registered with ClinicalTrials.gov identifier: NCT03315364.

Anti-cancer effects of DHP107 on canine mammary gland cancer examined through in-vitro and in-vivo mouse xenograft models

“…The recently developed oral paclitaxel (DHP107) is a safe and efficient treatment option for canine cancers based on its efficacy and safety results in various human cancers [ 20 , 22 , 23 ]. The paclitaxel used in this study is composed of monoolein, tricaprylin, and Tween 90, and it exerts its effect by interacting with bile acids and spontaneously forming ‘micelles’ with a diameter of approximately 10 µm in the intestine [ 17 ].…”

“…DHP 107 , a novel oral paclitaxel containing monoolein, tricaprylin, and polysorbate 80, is designed to be mucoadhesive, facilitating adhesion to mucosal cells in the gastrointestinal tract [ 21 ]. It has been approved by the United States Food and Drug Administration as a treatment for gastric cancer, and its therapeutic effects have been demonstrated in several cancers in humans [ 20 , 22 , 23 ]. Recently, various studies have been conducted on whether paclitaxel in a new formulation can be used as a therapeutic agent for animals with various cancers [ 24 – 28 ].…”