A novel oral paclitaxel and HM10381 (oraxel)-treated metastatic breast cancer: A phase I study (KX-ORAX-CN-007).

1104 Background: This phase I study assessed the pharmacokinetics, safety, antitumor activity of oral paclitaxel and HM10381 (Oraxel) in patients with metastatic breast cancer. Methods: Oraxol (oral paclitaxel 205 mg/m2 plus HM30181A 15 mg) daily for 3 consecutive days weekly for up to 16 weeks was administered to patients. The primary objective endpoint was pharmacokinetic analysis. The secondary endpoint were objective response rate (ORR) and safety. For pharmacokinetic analysis, timed blood samples were collected. Results: Twenty-four female patients were enrolled from Apr 2019 to Aug 2019. The median age was 53 years (range: 35 to 70 years). The mean lines and median line of treatment were 2.5 and 2, respectively. Previous breast cancer treatments included chemotherapy in 23 (96%) patients, hormonal therapy in 20 (83%) patients. Prior taxanes therapy was reported in 20 (83%) patients. There were 15 patients in efficacy dataset. The best ORR (Investigator) was PR in 40%, SD in 53%, and PD in 7%. The best overall response rate (ICRRC) was PR in 36%, SD in 57%, and PD in 7% of patients. There were no hypersensitivity-type reactions. Adverse events of interest neutropenia, neurotoxicity, and diarrhea were reported as 20 (83%)，7 (29%) and 11 (46%), retrospectively. A total of 15 (63%) patients experienced Grade ≥3 TEAEs, including neutrophil count decreased in 11 (46%) patients, WBC count decreased in 8 (33%) patients. Treatment related SAE was reported in 1 (4.17%) patient experienced febrile neutropenia, pneumonia, and septic shock. The PK data indicated that the efficacy response is not associated with oral paclitaxel exposure parameters AUC or Cmax. Conclusions: The study showed that Oraxol as novel oral chemotherapy agent shows promising antitumor activity in patients with metastatic breast cancer, manageable toxicity, and no hypersensitivity-type reactions. Clinical trial information: NCT04993040.