Open-label Phase 1b2 Study of HER3-DXd Alone and with Other Drugs in Patients With Advanced Inoperable Breast Cancer After T-DXd Treatment

What this Trial Is About

Researchers are evaluating HER3-DXd monotherapy and its combination with other cancer treatments in patients with advanced breast cancer ABC who have progressed after treatment with T-DXd. This open-label, multicenter phase 1b2 study focuses on safety, tolerability, and effectiveness of these therapies. The first two modules assess HER3-DXd with olaparib in HER2-low and HER2-positive ABC and HER3-DXd alone in HER2-low ABC after progression on T-DXd. Participants receive intravenous HER3-DXd monotherapy at 5.6 mgkg every 21 days in initial safety and dose-finding parts. In the dose expansion phase, patients receive the recommended phase 2 dose of HER3-DXd alone or combined with olaparib. Treatment continues in modules designed to explore monotherapy and combination therapy effects, with dosing schedules maintained every 21 days. Participants undergo safety and response evaluations including monitoring for dose-limiting toxicities, laboratory abnormalities, and radiographic signs of lung conditions over 21 months for early parts and up to 51 months for efficacy assessments. Researchers measure objective response rates, duration of response, progression-free survival, and clinical benefit rate. Patients provide biopsies and undergo routine laboratory and imaging assessments while treatment modifications due to side effects are tracked. The study spans several years with ongoing safety and pharmacokinetic evaluations.

Dose-Expansion Modular Study To Explore the Safety, Tolerability, and Anti-tumor Activity of HER3- DXd Monotherapy and Combinations in Patients With Inoperable Advanced Breast Cancer (ABC) After Progression on T-DXd