Safety and 5-year survival following treatment with leronlimab plus physician’s choice combination therapy in patients with metastatic triple-negative breast cancer.

Abstract

e13109 Background: There is a significant unmet need among patients with PD-L1 low/negative metastatic triple-negative breast cancer (mTNBC). >95% of TNBCs are positive for C-C chemokine receptor 5 (CCR5). Leronlimab (LRM) is a humanized monoclonal antibody given subcutaneously which blocks CCR5 and in a preclinical model reduced TNBC metastasis by more than 98%. Methods: In this post hoc analysis LRM safety and efficacy data were pooled from 28 mTNBC patients from 3 clinical trials (NCT03838367; NCT04313075; NCT04504942). LRM was given weekly at a dose of 350 mg (N=10), 525 mg (N=15), or 700 mg (N=3) in combination with various chemotherapies ± immune checkpoint inhibitors (ICI). PD-L1 staining (LifetracDx) was measured on cancer-associated macrophage-like cells (CAMLs) and circulating tumor cells (CTCs) prior to and after (≈40 days) LRM treatment. Results: Median age was 48.5 years (range 32-83) with a median of 2 prior metastatic therapies (range 0 to 5). Ten patients (35.7%) had non-visceral metastases; 18 (64.3%) had visceral metastases, including 7 (25.0%) with brain metastases. The most common treatment-emergent adverse events (TEAEs), at a rate of ≥10%, were fatigue (21.4%), headache (21.4%), anemia (10.7%), constipation (10.7%), nausea (10.7%), and decreased neutrophil count (10.7%) but with no febrile neutropenia events. Overall, 21.4% (6/28) patients reported any LRM treatment-related TEAE; of these none were classified as CTCAE grade >2. No patients discontinued treatment due to a LRM treatment-related TEAE. Overall, 35.7% (10/28) reported any serious TEAE; none of the serious TEAEs were considered related to LRM treatment. The median overall survival (OS) was 7.1 months. Survival at 1, 2, 3, 4, and 5 years was 35.7%, 21.4%, 17.9%, and 17.9%, 17.9%, respectively. OS among the 7 patients treated with LRM with an ICI, or followed by an ICI, was longer than among the remaining 21 patients (HR 4.14, 95% CI: 1.7–10.2; P=0.0041). For patients with available data, upregulation from baseline of PD-L1 was observed on CAMLs/CTCs in 76% (16/21) of patients. All five patients treated with LRM [525 mg (N=4), or 700 mg (N=1)] with an ICI, or followed by an ICI, and who significantly upregulated PD-L1, remained alive at 5 years. Conclusions: In this post hoc analysis LRM was well tolerated with no LRM treatment-related TEAEs leading to treatment discontinuation and no LRM treatment-related TEAEs graded as CTCAE >2. A 5-year OS rate of 17.9% (5/28) in this advanced population is encouraging. All 5 patients with PD-L1 upregulation treated with LRM with an ICI, or followed by an ICI, remained alive at 5 years suggesting a correlation with durable responses. These findings support the hypothesis that LRM may enhance PD-L1 expression on CAMLs/CTCs, potentially priming tumors for improved responses to ICIs. Confirmatory phase 2 studies in mTNBC are planned. Clinical trial information: NCT03838367 (N=10); NCT04313075 (N=16); and NCT04504942 (N=2).