A Phase I Trial of Evorpacept, Lenalidomide, and Rituximab for Patients with B-Cell Non-Hodgkin Lymphoma
Paolo Strati, Lei Feng, Andrey Tyshevich, Darya Shavronskaya, Julia Alesse, Noel English, Elizabeth Sheehan, Nikita Syzrantsev, Alexander Nesmelov, Tony Zhuang, Dai Chihara, Jason R. Westin, Sairah Ahmed, Luis Fayad, Jared Henderson, Kylie Dent, Elizabeth McChesney, Sattva S. Neelapu, Christopher R. Flowers
Abstract
PURPOSE: SIRPα+ macrophages can mediate resistance to lenalidomide and rituximab in patients with B-cell non-Hodgkin lymphoma (B-NHL). Evorpacept (ALX148) is a novel CD47 blocker that abrogates interactions between lymphoma cells and SIRPα+ macrophages. PATIENTS AND METHODS: Adult patients with B-NHL who had received at least two prior lines of systemic therapy were included in this single-arm phase I study (NCT05025800). Evorpacept was administered intravenously, in a 28-day cycle, until progression at two dose levels (DL): 30 mg/Kg on day (D) 1 and D15 (DL1) or 60 mg/Kg on day 1 (DL2); rituximab 375 mg/m2 i.v. was given weekly during cycle 1 and on D1 during cycles 2 to 6; and lenalidomide 20 mg was given orally from D1 to D21 during cycles 1 to 6. Single-cell RNA sequencing was performed on tumor biopsies collected before treatment and during cycle 1. RESULTS: Twenty patients were included in this study. The median age was 61 (27-85) years, and 18 patients (90%) had indolent B-NHL. Three patients were treated at DL1, 17 at DL2, and no dose-limiting toxicity was observed. The most common grade 3 to 4 adverse events included neutropenia (60%), infections (30%), and alanine transferase increase (15%). Sixteen (80%) patients achieved complete response, and after a median follow-up of 28 months, 2-year progression-free survival rate was 69%. During treatment, a significant increase in T cells and macrophages was observed, and macrophage pathways associated with anti-tumoral activity were upregulated. CONCLUSIONS: Evorpacept plus lenalidomide and rituximab has a safe toxicity profile and promising anti-tumoral activity, and induces favorable biological effects on the tumoral immune microenvironment.