Abstract OT1-17-01: Solti-1716. Targeting with pembrolizumab + paclitaxel non-luminal by PAM50 hormone receptor-positive/HER2-negative advanced/metastatic breast cancer patients who have progressed on or after CDK4/6 inhibitor treatment (TATEN trial)
Authors: Ciruelos Eva , Muñoz Montserrat , Oliveira Mafalda , Chic Nuria , Hernando Cristina , Viruzuela Juan Antonio , Vázquez Silvia , Blanch Salvador , Paré Laia , Salvador Fernando , Villagrasa Patricia , Pascual Tomás , Prat Aleix 
Published: March 2022

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, for whom no standard treatment exists. 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 (TN) BC and several trials evaluating the action of immune checkpoint inhibitors are ongoing both in TN and in HR+/HER2- BC. TATEN study aims to evaluate the combination of pembrolizumab and chemotherapy in metastatic HR+/HER2-negative, PAM50 non-luminal BC.Study design. TATEN is an open-label, single arm, multicenter phase II study evaluating pembrolizumab in combination with paclitaxel in patients with locally advanced or metastatic PAM50 non-luminal HR+/HER2- BC who had recurrence or progression after therapy with a CDK4/6 inhibitor plus endocrine therapy. 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 evaluable 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 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 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. As of July 2021, 10 patients have been enrolled in 7 sites in Spain. Clinical trial identification: NCT04251169. Acknowledgements:This study is financially supported by MSD

Citation Format: Eva Ciruelos, Montserrat Muñoz, Mafalda Oliveira, Nuria Chic, Cristina Hernando, Juan Antonio Viruzuela, Silvia Vázquez, Salvador Blanch, Laia Paré, Fernando Salvador, Patricia Villagrasa, Tomás Pascual, Aleix Prat. Solti-1716. Targeting with pembrolizumab + paclitaxel non-luminal by PAM50 hormone receptor-positive/HER2-negative advanced/metastatic breast cancer patients who have progressed on or after CDK4/6 inhibitor treatment (TATEN trial) [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr OT1-17-01.