Abstract PD3-01: Results from KATE2, a randomized phase 2 study of atezolizumab (atezo)+trastuzumab emtansine (T-DM1) vs placebo (pbo)+T-DM1 in previously treated HER2+ advanced breast cancer (BC)
Authors: Emens LA , Esteva F , Beresford M , Saura C , De Laurentiis M , Kim S-B , Im S-A , Patre M , Wang Y , Mani A , Liu H , de Haas S , Loi S 
Published: May 2019

Abstract
Background
T-DM1 has improved PFS and OS in HER2+ advanced BC patients (pts) who previously progressed on trastuzumab and a taxane (Verma NEJM 2012). Preclinical data show that atezo (anti–PD-L1) inhibits PD-L1 binding to PD-1 and B7.1 to restore antitumor immunity. PD-L1 is often expressed on tumor-infiltrating immune cells (IC) in BC. KATE2 (NCT02924883) is the first study to assess atezo combined with T-DM1 in previously treated HER2+ advanced BC.
Method
Eligible pts had HER2+ advanced BC previously treated with trastuzumab and a taxane and progressed on treatment for metastatic disease or within 6 mo of adjuvant therapy. Pts were randomized 2:1 to atezo 1200 mg or pbo+T-DM1 3.6 mg/kg IV q3w (crossover not permitted). The primary endpoint was investigator-assessed PFS per RECIST v1.1. Additional endpoints included OS, ORR, DoR (secondary), PFS in the PD-L1+ subgroup (exploratory) and safety. Data cutoff: 11 Dec 2017.
Result
133 pts were randomized to atezo+T-DM1 and 69 pts to pbo+T-DM1. 49% and 46% received prior pertuzumab for metastatic BC; median duration of pertuzumab treatment was 10 and 13 mo, respectively. Median follow-up was 8.5 and 8.4 mo, respectively. Efficacy in the ITT population and biomarker subgroups are shown. PFS HR was 0.82 (95% CI: 0.55, 1.23); p=0.3332. At data cutoff, 13 OS events (10%) in the atezo+T-DM1 arm and 8 (12%) in the pbo+T-DM1 arm had occurred. mDoR was not reached. 44% and 41% of safety-evaluable pts had an AE of Gr ≥3 with atezo+T-DM1 and pbo+T-DM1, respectively. The most common was thrombocytopenia (13% and 4%). The incidence of serious AEs (SAEs) was 33% with atezo+T-DM1 and 19% with pbo+T-DM1, with the most common being Gr 1-2 pyrexia with atezo+T-DM1 (5%) and abdominal pain (3%) and seizure (3%) with pbo+T-DM1. AE rates leading to atezo/pbo or T-DM1 discontinuation were 25% and 15%, respectively, with atezo+T-DM1 and 15% and 13% with pbo+T-DM1. 1 patient in the atezo+T-DM1 arm had a drug-related Gr 5 AE (hemophagocytic syndrome).
ITT and Biomarker Subgroups: Efficacy Atezo+T-DM1 (n=133)Pbo+T-DM1 (n=69)mPFS, mo8.26.86-mo PFS, %585112-mo PFS, %3834ORR, %a4543CR67PR3936PD-L1 IHCb PD-L1+PD-L1-PD-L1+PD-L1-Patients, n57762742mPFS, mo8.56.84.18.2ORR, %a54403350Stromal TILsc TIL-high (≥5%)TIL-low (&lt;5%)TIL-high (≥5%)TIL-low (&lt;5%)Patients, n80454025mPFS, mo8.55.55.3NAORR, %a48383848HER2c IHC3+IHC0-2+IHC3+IHC0-2+Patients, n103305613mPFS, mo8.55.98.04.0ORR, %a52234631aORR-evaluable pts (measurable disease at baseline): n=132 in atezo+T-DM1 arm. bPD-L1+, IC1/2/3; PD-L1–, IC0; measured per the VENTANA SP142 IHC assay. cPost hoc exploratory analyses.
Conclusion
Atezo+T-DM1 did not demonstrate a clinically significant PFS benefit vs pbo+T-DM1; OS and DoR data are not yet mature. Numerically higher PFS and ORR were seen with atezo+T-DM1 in PD-L1+ pts. T-DM1 safety in both arms was consistent with its known profile. Although the combination of atezo+T-DM1 showed a numerically higher incidence of SAEs and discontinuation of atezo due to an AE, rates of Gr 3-5 AEs were similar between arms. Additional biomarker data, including gene expression and mutation data, will be presented.
Citation Format: Emens LA, Esteva F, Beresford M, Saura C, De Laurentiis M, Kim S-B, Im S-A, Patre M, Wang Y, Mani A, Liu H, de Haas S, Loi S. Results from KATE2, a randomized phase 2 study of atezolizumab (atezo)+trastuzumab emtansine (T-DM1) vs placebo (pbo)+T-DM1 in previously treated HER2+ advanced breast cancer (BC) [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr PD3-01.