Abstract OT-13-04: Solti-1716. Targeting non-Luminal disease by PAM50 with pembrolizumab + paclitaxel in Hormone Receptor-positive/HER2-negative advanced/metastatic breast cancer patients who have progressed on or after CDK 4/6 inhibitor treatment (TATEN trial)
Authors: Ciruelos Eva , Pascual Tomás , Chic Nuria , Muñoz Montserrat , Bermejo Begoña , Virizuela Juan Antonio , Oliveira Mafalda , Vázquez Silvia , Blanch Salvador , Paré Laia , Salvador Fernando , Villagrasa Patricia , Prat Aleix 
Published: February 2021

Abstract
Background. Patients with metastatic Hormone Receptor-positive/HER2-negative (HR+/HER2-) breast cancer (BC) are usually treated with CDK4/6 inhibitors combined with endocrine therapy (ET) as first line treatment. The addition of CDK4/6 inhibitors to endocrine therapy has demonstrated improved progression free survival (PFS), overall response rate (ORR) and more recently overall survival (OS). However, there is a 20% of patients who do not benefit from these drugs and those who respond eventually progress to the treatment. Notably, there is no standard treatment for patients progressing to CDK4/6 inhibitors. The information provided by the intrinsic subtypes (PAM50) highlight the potential value of BC molecular classification as a prognosis and predictive marker. Within HR+/HER2- disease, patients with non-luminal subtypes (HER2-enriched and Basal-like) present poorer prognosis than those with luminal subtypes, may be more sensitive to chemotherapy, and have higher expression of immune-related genes and tumor infiltrating lymphocytes (TILs). Recently, immunotherapy has been approved for treating metastatic triple negative breast cancer and several trials evaluating the action of immune checkpoint inhibitors are ongoing, including HR+/HER2- BC patients. TATEN study aims to evaluate the combination of pembrolizumab and chemotherapy in metastatic HR+/HER2-, PAM50 non-luminal BC.
Study design. TATEN is an open-label, single arm, multicenter phase II study evaluating treatment with pembrolizumab in combination with paclitaxel in patients with locally advanced or metastatic non-luminal HR+/HER2- BC who had recurrence or progression while receiving previous therapy with a CDK4/6 inhibitor plus endocrine therapy in the adjuvant and/or metastatic setting. Tumor samples collected during advanced/metastatic disease are mandatory. No prior chemotherapy for inoperable locally advanced or metastatic BC is permitted. Eligible patients will receive pembrolizumab 200 mg every 3 weeks (on day 1 of each 21-day cycle, beginning in Cycle 1) in combination with paclitaxel 80 mg/m2 administered at days 1, 8, 15 of each 21-day cycle beginning at cycle 2. The primary endpoint of the study is to evaluate ORR according to RECIST V1.1. The study will use a Simon’s 2-stage design and will include up to 46 patients. If 6 or more responses are observed in up to 15 patients in the first stage, the trial will continue to the second stage and 31 additional patients may be evaluated for a maximum total of 46 evaluable patients. The null hypothesis will be rejected if 19 or more responses are observed. Tumor assessments will be performed every 9 weeks. Secondary endpoints include clinical benefit rate (CBR), PFS, duration of response (DoR), time to response (TtR), OS, as well as to assess the correlation of clinical benefit (ORR, PFS) with PD1 mRNA expression and early dynamic changes in ctDNA after 1 cycle of pembrolizumab (collection of blood samples at Cycle 1 Day 1, Cycle 2 Day 1 and end of treatment are mandatory). Safety and tolerability of the combination will also be assessed. Exploratory objectives include to determine ORR, PFS, DoR and TtR based on iRECIST and to identify predictive biomarkers of response to pembrolizumab plus paclitaxel.
Patients will be enrolled in 7 sites in Spain. Recruitment started in July 2020. This study is financially supported by MSD. NCT04251169.
Citation Format: Eva Ciruelos, Tomás Pascual, Nuria Chic, Montserrat Muñoz, Begoña Bermejo, Juan Antonio Virizuela, Mafalda Oliveira, Silvia Vázquez, Salvador Blanch, Laia Paré, Fernando Salvador, Patricia Villagrasa, Aleix Prat. Solti-1716. Targeting non-Luminal disease by PAM50 with pembrolizumab + paclitaxel in Hormone Receptor-positive/HER2-negative advanced/metastatic breast cancer patients who have progressed on or after CDK 4/6 inhibitor treatment (TATEN trial) [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr OT-13-04.