AACR Annual Meeting 2022 Itinerary Planner Home Print Page Share Page
Session PO.CT01.01 - Phase I Clinical Trials 1
CT156 / 24 - Changes in circulating tumor associated cells predicts progression free and overall survival in metastatic TNBC patients after induction of the anti-CCR5 drug leronlimab
April 11, 2022, 1:30 PM - 5:00 PM
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 IgG4? 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.
