266TiP A phase II, randomized, open- labelled study to evaluate low-dose pembrolizumab in addition to neoadjuvant chemotherapy for triple-negative breast cancer (TNBC)

Abstract

Background Breast cancer is the most common malignancy diagnosed in women worldwide. Triple negative breast cancer is the most aggressive subtype, accounting for nearly 15% of all breast cancers worldwide with upto one third of all breast cancers in South east Asian region.The addition of pembrolizumab to neoadjuvant chemotherapy improved the pathological response rates and event free survival in patients with triple negative breast cancer. However in most low and middle income countries, immunotherapy remains inaccesible due to its high cost. Lower doses of immune checkpoint inhibitors (nivolumab and pembrolizumab) have been shown to be effective in several cancers, including head and neck cancers, Hodgkin’s lymphoma, etc. Ex vivo IL2 stimulation for the purpose of evaluating PD-1 receptor modulation revealed total peripheral target engagement beginning at 1 mg/kg and lasting for at least 21 days, with no discernible difference between 1, 3, and 10 mg/kg. Therefore, we designed this study to evaluate a lower dose of pembrolizumab in addition to neoadjuvant chemotherapy in patients with TNBC as a cost-effective intervention. Trial design This is a phase II, randomized, open-labelled, parallel-group trial. Eligible patients will be randomized (1:1) to either of the two treatment groups. Patients in the control arm will be administered standard of care chemotherapy [4 cycles of dose-dense doxorubicin(60mg/m2) and cyclophosphamide(600mg/m2), followed by 4 cycles of dose-dense paclitaxel (175mg/m2)]. Patients in the experimental arm will receive 3 doses of pembrolizumab 50mg every 6 weeks along with neoadjuvant dose-dense chemotherapy. The primary objective of the study is to compare the pathological complete response with the addition of low-dose pembrolizumab to neoadjuvant chemotherapy in patients with TNBC.Secondary objectives include invasive disease-free survival and quality of life assessment.