A Phase I Trial of Evorpacept, Lenalidomide and Rituximab for Patients with B-cell Non-Hodgkin Lymphoma

Authors

Paolo Strati
Lei Feng
Andrey Tyshevich
Darya Shavronskaya
Julia Alesse
Noel English
Elizabeth Sheehan
Nikita Syzrantsev
Alexander Nesmelov
Tony Z Zhuang
Dai Chihara
Jason R Westin
Sairah Ahmed
Luis E Fayad
Jared Henderson
Kylie Dent
Elizabeth McChesney
Sattva S Neelapu
Christopher R Flowers

Publication Date

7-29-2025

Journal

Clinical Cancer Research

DOI

10.1158/1078-0432.CCR-25-1826

PMID

40729376

PMCID

PMC12370181

PubMedCentral® Posted Date

8-22-2025

PubMedCentral® Full Text Version

Author MSS

Abstract

Introduction: SIRPα+ macrophages can mediate resistance to lenalidomide and rituximab (R2) 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.

Methods: Adult patients with B-NHL who had received at least 2 prior lines of systemic therapy were included in this single arm phase I study (NCT05025800). Evorpacept was administered intravenously (IV), 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 IV was given weekly during cycle 1, and on D1 during cycles 2-6; lenalidomide 20 mg was given orally on D1-21 during cycles 1-6. Single-cell RNA sequencing was performed on tumor biopsies collected before treatment and during cycle 1.

Results: Twenty patients were included in this study. Median age was 61 (27-85) years and 18 (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 3-4 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 macrophages pathways associated with anti-tumoral activity were upregulated.

Conclusions: ER2 has a safe toxicity profile, promising anti-tumoral activity, and induces favorable biological effects on the tumoral immune microenvironment.

Published Open-Access

yes

Recommended Citation

Strati, Paolo; Feng, Lei; Tyshevich, Andrey; et al., "A Phase I Trial of Evorpacept, Lenalidomide and Rituximab for Patients with B-cell Non-Hodgkin Lymphoma" (2025). Faculty, Staff and Student Publications. 4884.
https://digitalcommons.library.tmc.edu/uthgsbs_docs/4884