A Phase I/II Study of FWD1802 in Patients With ER+/HER2- Advanced BC.

A Phase I/II, Open-label study to assess the safety, tolerability, pharmacokinetic, and antitumor efficacy of FWD1802 monotherapy in patients with ER+/HER2- unresectable locally advanced or metastatic breast cancer. This clinical trial aims to explore the role of FWD1802 in the ER+/HER2- advanced breast cancer patient population. The primary objectives are to address the following questions: Phase I Study: Determine the Recommended Phase II Dose (RP2D) and/or Maximum Tolerated Dose (MTD) of FWD1802 in patients with ER-positive, HER2-negative locally advanced or metastatic breast cancer. Phase II Study: To evaluate the efficacy of FWD1802 at the RP2D in patients with ESR1-mutated ER-positive/HER2-negative locally advanced or metastatic breast cancer, using objective response rate (ORR) as the efficacy endpoint.

This is a phase I/II, multicenter, open-label, first-in-human study of FWD1802 in patients with locally advanced or metastatic breast cancer that is estrogen receptor (ER)-positive/human epidermal growth factor receptor 2 (HER2)-negative (Phase II: restricted to patients with ESR1-mutated). It consists of three parts: the FWD1802 dose-escalation phase (Phase I Part A), the FWD1802 dose-expansion phase (Phase I Part B), and the dose-expansion study of FWD1802 in patients with ESR1 mutations (Phase II study). Each study phase includes a screening period (up to 4 weeks), a treatment period (maximum treatment duration of 2 years; continuation beyond 2 years is permitted if the investigator judges the subject is still benefiting, with agreement from both the investigator and sponsor), and a follow-up period. The Phase II study includes a pre-screening period; patients with unknown mutation status may undergo testing that includes ESR1 mutation status prior to the screening period. Phase I Part A is the FWD1802 dose-escalation study: A dose-escalation trial using a combination of an "accelerated titration" design and a "3+3" design is planned, with a maximum of 27 subjects to be enrolled. The Safety Monitoring Committee (SMC) will evaluate pharmacokinetic (PK), pharmacodynamic (PD), efficacy, and safety data to guide the determination of potentially effective doses for Part B and the Phase II study. Phase I Part B is the FWD1802 dose-expansion study: Based on safety, PK, PD, and other data obtained from Part A, 2 to 4 dose cohorts will be selected for further exploration of FWD1802's PK profile and the recommended phase 2 dose (RP2D). Each dose cohort will be expanded to include up to 10 subjects (including subjects from the corresponding dose cohort in Part A). The SMC will decide which dose cohorts to expand and the timing of expansion based on information obtained from Part A. Dose expansion may proceed concurrently with the dose-escalation phase, within dose ranges already confirmed as safe by the SMC. The Phase II study is cohort expansion study targeting the population with ESR1 mutations: Enrolled subjects will have ER-positive, HER2-negative breast cancer with ESR1 mutations. One to two dose levels will be selected for exploration, with each dose level enrolling no more than 30 subjects, for a maximum total enrollment of 60 subjects.