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
Trial Parameters
Brief Summary
ICARUS-BREAST02 is an open-label, multicenter, phase 1b/2, platform study that aims to evaluate the safety, tolerability, and efficacy of HER3-DXd monotherapy and in combination with other anti-cancer agents in patients with ABC. The first 2 modules will evaluate: i. safety and efficacy of HER3-DXd with olaparib in patients with HER2-low and HER2-positive ABC progressed on T-DXd (Module 1) and HER3-DXd monotherapy in patients with HER2-low ABC progressed on T-DXd (Module 0). The main objective of Part 1 is to assess the safety and tolerability of HER3-DXd monotherapy and combination and to determine the recommended phase 2 dose (RP2D) of the combination containing HER3-DXd. The main objective of Part 2 is to assess the efficacy of study therapies in each module based on investigator assessment as evaluated by the objective response rate (ORR) at 6 months.
Eligibility Criteria
Inclusion Criteria: 1. Patients must have received prior treatment with T-DXd and presented disease progression while on T-DXd treatment or within 2 months from T-DXd interruption/discontinuation for any reason, without requiring to be the last line of treatment. Patients who have received other lines of treatment after T-DXd and before study entry is capped at 10 patients for each cohort. 2. Patients with HER2-positive tumors must have received prior treatment with trastuzumab and taxanes. They may have received prior treatment with T-DM1 and pertuzumab. 3. Patients with HER2-low tumors must have been treated with taxanes. Patients with HR-positive tumors must have received ET and CDK4/6 inhibitors (patients may have received prior treatment with sacituzumab govitecan) If a patient has a tumor that was previously HER2-pos and became HER2-low, she/he will be included in cohort 2 and meet the inclusion criteria for HER2-low tumors. If a patient has a tumor that was previously HR-pos and