Abstract CT156: Changes in circulating tumor associated cells predicts progression free and overall survival in metastatic TNBC patients after induction of the anti-CCR5 drug leronlimab
Authors: Adams Daniel L. , Raghavakaimal Ashvathi , Tang Cha-Mei , Gardner Kirby P. , Ray Nitya G. , Pourhassan Nader 
Published: June 2022

Abstract
Background: Metastatic triple negative breast cancer (mTNBC) is a highly invasive breast cancer subtype that has limited treatment options and poor clinical outcomes for patients. Recently, the C-C chemokine receptor 5 (CCR5) was identified in preclinical models as a potential drug target that inhibits pro-migratory tumor progression in breast cancer by blocking tumor motility and subsequent tumor cell spread. Leronlimab (PRO140), a humanized IgG4κ monoclonal antibody, is a competitive inhibitor of CCR5, with 3 active clinical trials ongoing in TNBC patients. Here we report on a preliminary pooled analysis of n=28 mTNBC patients to evaluate effects of Leronlimab on circulating tumor-associated cells (TACs) found in peripheral blood as an early predictor of drug response, with end point outcomes of progression free survival (PFS) and Overall Survival (OS).
Methods: Blood samples were drawn from mTNBC patients from 3 blinded prospective clinical drug studies, Phase 1b/2 (NCT03838367), Compassionate Use (NCT04313075), and Basket Study (NCT04504942) to evaluate the predictive value of TACs, measured by the LifeTracDx assay. All subjects received ≥1 dose of Leronlimab (range 1-33 doses), ranging from 350mg - 700mg, with 4 subjects having dose escalation. Anonymized blinded peripheral blood samples were available from (n=28) patients, obtained as part of the exploratory portion of the trials, prior to drug induction (BL) and after one treatment cycle (T1), ~26 days. TACs, i.e. Circulating tumor cells (CTCs) and Cancer Associated Macrophage-like cells (CAMLS), were isolated using a low-flow CellSieve microfiltration system and changes in TACs were quantified by the LifeTracDx assay. A univariate analysis was used to analyze changes in TACs to predict for PFS and OS over 12 months.
Results: A total of 28 mTNBC patients were pooled from Phase 1b/2 (n=10), Compassionate Use (n =16), and Basket Study (n=2) all of which had available BL blood samples, or T1 samples. CTCs were found in 29% (n=8/28) of patients at BL, and CAMLs were found in 96% (n=27/28). Evaluating CTC change was limited, as only 5 patients had any CTC increase, although the absence or drop of CTCs at T1 was significant for better PFS (HR=13.7 CI 95% 2.0-93.8, p=0.0296) and better OS (HR=397.7 CI 95% 19.3-100+, p=0.0019). By comparison, CAMLs or CTCs were evaluable in 100% of patients, with an increases of either population at T1 also significantly predicting for worse PFS (HR=5.8 CI 95% 1.4-23.6, p=0.0354) and worse OS (HR=36.0 CI 95% 6.2-207.6, p=0.0004).
Conclusions: We observed that treatment with Leronlimab resulted in rapid decreases in the presence of multiple populations of TACs in 75% of patients, which also significantly correlated with better PFS and OS after 1 year analysis.
Citation Format: Daniel L. Adams, Ashvathi Raghavakaimal, Cha-Mei Tang, Kirby P. Gardner, Nitya G. Ray, Nader Pourhassan. Changes in circulating tumor associated cells predicts progression free and overall survival in metastatic TNBC patients after induction of the anti-CCR5 drug leronlimab [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr CT156.