Abstract PS12-19: Title:peripheral blood immuneimpactsin arandomizedphase iiclinical trial ofprogrammed death 1 (pd-1) blockadecombined with platinum-based chemotherapy in patients with metastatic triple negative breast cancer (mtnbc)
Authors: Obeid Elias , Fang Judy , McFarlane Alex W , Shchaveleva Irina , Souchuck Shauna , Campbell Kerry S , Goldstein Lori J 
Published: February 2021

Abstract
Background: PD-1 blockade has shown promising clinical activity in mTNBC. We designed an investigator-initiated multi-center clinical trial consisting of a Safety run-in, into a randomized phase II trial of combination pembrolizumab (P) with carboplatin (C) and gemcitabine (G) in patients with mTNBC. A detailed characterization of peripheral immune cell changes may help in understanding responses in mTNBC to immune checkpoint inhibition. Correlative studies for the purpose of understanding the effect of combining chemotherapy (CT) simultaneously with checkpoint inhibition on the peripheral immune response are planned as part of this clinical trial.
Methods: Patients with a diagnosis of mTNBC are recruited to this trial with a Safety Run-in (N = 6 subjects), followed by a randomized design of C + G with/without P (2:1 randomization, N = 75). Treatment consists of P 200 mg on day 1 of each 21-day cycle, and C (AUC2) + G (800mg/m2) on days 1 and 8 for cohort A, and C (AUC2) + G (800mg/m2) for cohort B. Patients are consented for a peripheral blood (PB) collection pre-treatment on day 1 of cycle 1, and post-treatment on day 1 of cycle 3, in order to phenotype immune changes by flow-cytometry.
Results: A total of 60 patients have been consented, 42 patients were enrolled (6 on safety run-in, 36 on the randomized part II). Of those on the randomized part II, blood samples from 17 patients have been analyzed from cycle 1 day 1 and cycle 3 day 3. A decreased expression of PD-1 on effector and memory subsets of both CD4+ and CD8+ T cells from C1D1 to C3D1 was observed in blood from both cohorts, especially cohort A. We found an increased % NK, CD4+ T and CD8+ T cell subsets expressing the activation marker, CD69, in cohort A, but not cohort B, reflecting activation by pembrolizumab.​ There was a parallel increased expression of the proliferative marker, Ki67, in CD56bright (immature) NK cells and effector memory CD8+ T cells in blood from C1D1 to C3D1 in cohort A. We also found an increased % CD56bright (immature) NK and effector memory CD4+ T cells expressing the exhaustion marker, CD39, which was consistent with increased expression of the activation marker, CD69.
Conclusions: Although comprising a limited number of patients in this early analysis, our correlative studies found evidence for effective immune stimulation upon combining CT with the PD-1 blockade. The randomized nature of this trial, with our planned pre and post treatment blood collection will be helpful in understanding response to immune check point inhibition combined with chemotherapy in mTNBC. Correlation with absolute lymphocyte counts and outcomes data is planned and will be presented.
Citation Format: Elias Obeid, Judy Fang, Alex W McFarlane, IV, Irina Shchaveleva, Shauna Souchuck, Kerry S Campbell, Lori J Goldstein. Title:peripheral blood immuneimpactsin arandomizedphase iiclinical trial ofprogrammed death 1 (pd-1) blockadecombined with platinum-based chemotherapy in patients with metastatic triple negative breast cancer (mtnbc) [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 PS12-19.