Abstract CT233: Phase Ib/II study of leronlimab (PRO 140) combined with carboplatin in CCR5+ mTNBC patients
Authors: Cristofanilli Massimo , Dolezal Milana , Lalezari Jay , Rui Hallgeir , Patterson Bruce , Tang Cha-Mei , Adams Daniel , Zhang Qiang , Kazempour Kazem , Pourhassan Nader , Rabb Natalie , Dhody Kush 
Published: September 2020

Abstract
Introduction: Triple Negative Breast Cancer (TNBC) represents the most deadly form of invasive disease. It is associated with clinical and pathological features of highly proliferative and rapidly spreading cancer demonstrating higher incidence in younger women, particularly of African-American ethnicity and accounting for a disproportionately high percentage of early development of metastatic disease and breast-cancer-related death. While chemotherapy remains the main treatment option for both primary and metastatic TNBC (mTNBC) there is no optimized therapy for its management due to tumor heterogeneity, leaving the condition with an unmet medical need. Recent preclinical research demonstrated an important role for chemokine receptor type 5 (CCR5) in modulating cell migration and immune microenvironment suggesting a potential new therapeutic target in mTNBC [Jiao X et al, Can Res 2018;78:1657-71]. Leronlimab (PRO 140) is a humanized IgG4,к monoclonal antibody (mAb) to the C-C chemokine receptor type 5 (CCR5). Leronlimab has been administered and generally well tolerated in more than 750 healthy and HIV-1 infected individuals in Phase I/II/III studies. An ongoing Phase Ib/II study is being conducted to assess the safety and clinical outcomes of leronlimab combined with carboplatin in patients with untreated CCR5+ metastatic Triple Negative Breast Cancer (mTNBC). Methods: Eligible patients are required to have confirmed HER2 negative, ER &lt;1%, PR&lt;1% and demonstrate CCR5+ by immunohistochemistry assay (IHC) (&gt;10% of primary or metastatic cancer cells shows membranous staining and/or high predominance of CCR5+ tumor-infiltrating leukocytes (see representative IHC staining images below) Phase Ib of the CD07_TNBC study is a multicenter, single arm, dose escalation phase with 3 dose levels of leronlimab administered in combination with a fixed dose of carboplatin at AUC 5. The starting dose is 350 mg with escalation to 525 mg and 700 mg in the absence of dose-limiting toxicities. Leronlimab is administered as subcutaneous injection in the abdomen weekly and can be self-administered by subjects at home after proper training by a healthcare professional. Carboplatin is administered at AUC 5 every 3 weeks. The maximum tolerated dose (MTD) of leronlimab determined during the Phase Ib portion will be administered to 30 patients during the Phase II portion of the study. Correlative Data: Blood samples are collected at Day 1 of each treatment cycle (every 21 days) to assess changes in circulating tumor cells (CTCs) and cancer associated macrophage-like cells (CAMLs) after treatment and to perform correlative analysis with CCR5 expression. Conclusions: Leronlimab (PRO 140), a CCR5 antagonist mAb, in combination with carboplatin is currently enrolling newly diagnosed mTNBC. The preliminary analysis shows safety and tolerability of the combination and continue to enroll patients with initial promising clinical activity, potentially suggesting the future availability of a new effective agent in the management of this serious condition.
Citation Format: Massimo Cristofanilli, Milana Dolezal, Jay Lalezari, Hallgeir Rui, Bruce Patterson, Cha-Mei Tang, Daniel Adams, Qiang Zhang, Kazem Kazempour, Nader Pourhassan, Natalie Rabb, Kush Dhody. Phase Ib/II study of leronlimab (PRO 140) combined with carboplatin in CCR5+ mTNBC patients [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr CT233.