329TiP KATE3: A phase III study of trastuzumab emtansine (T-DM1) in combination with atezolizumab or placebo in patients with previously treated HER2-positive and PD-L1–positive locally advanced or metastatic breast cancer

Abstract

T-DM1, a HER2-targeted antibody–drug conjugate, and atezolizumab, a PD-L1-targeted monoclonal antibody, have shown clinical benefit in HER2-positive and triple-negative breast cancer (BC), respectively. In addition to its cytotoxic effects, T-DM1 potentiates antitumor immunity with a synergistic effect observed in preclinical models when combining PD-L1 and HER2 inhibitors. Exploratory analyses of the randomized, phase 2 KATE2 study suggested a progression free survival (PFS) and overall survival (OS) benefit with atezolizumab plus T-DM1 compared to T-DM1 alone in pre-treated patients with HER2-positive and PD-L1-positive locally advanced (LA)/metastatic (M)BC. These data support further study of T-DM1 plus atezolizumab in this patient population. KATE3 (NCT04740918) is an ongoing randomized, multicenter, double-blind, Phase 3 study of T-DM1 with atezolizumab or placebo in trastuzumab- (± pertuzumab) and taxane-pretreated LA/MBC with centrally-determined HER2-positive and PD-L1–positive (assessed ≤6 months before study entry) unresectable LA/MBC. Patients must have received ≤2 prior lines of therapy for MBC and experienced disease progression during or after LA/MBC therapy or during or within 6 months after (neo)adjuvant therapy. Previous adjuvant T-DM1 is allowed if disease recurrence occurred >6 months after completing T-DM1 treatment. Previous treatment with CD137 agonists and PD-(L)1–targeted agents is allowed. Patients are randomized 1:1 to 3-weekly cycles of T-DM1 3.6 mg/kg and atezolizumab 1200 mg or T-DM1 3.6 mg/kg and placebo. Randomization is stratified by hormone receptor status, disease status, and world region. The multiple primary endpoints are investigator-assessed PFS and OS. Secondary endpoints include objective response rate, response duration, PFS assessed by a blinded independent central review committee, PFS and OS in those with brain metastases at baseline, central nervous system PFS, patient-reported outcomes, and safety. Approximately 350 patients will be enrolled at approximately 175 sites worldwide. NCT04740918. Medical writing support was provided by Tracy McNally, PhD, and Holly Strausbaugh, PhD, on behalf of Twist Medical, LLC, and funded by F. Hoffmann-La Roche, Ltd. F. Hoffmann-La Roche, Ltd.