FDA Fast Tracks Anti-CD127 Monoclonal Antibody for Acute Lymphoblastic Leukemia

4A10, a monoclonal antibody targeting interleukin-7 receptor alpha (IL-7Rα; CD127), has received fast track designation from the FDA for the treatment of patients with relapsed or refractory acute lymphoblastic leukemia (ALL).¹

The designation follows numerous positive FDA actions regarding 4A10, including clearance of the agent’s investigational new drug application, as well as an orphan drug designation and rare pediatric disease designation. The fast track designation, granted to agents that fill serious unmet medical needs, comes with several key regulatory advantages, including increased interactions with the FDA, rolling review of a biologics license application, and eligibility for priority review.²

Collectively, these efforts will facilitate the development and review of 4A10 to confront the substantial burden of ALL, the most common pediatric cancer worldwide,³ with an estimated prevalence exceeding 120,000 individuals in the United States as of 2022.⁴

"Children with many relapsed leukemias have very few effective therapies," said Eric Schafer, MD, associate professor at Baylor College of Medicine and Texas Children's Hospital and chair of the imminent 4A10 study, in a news release.¹ "Innovative approaches like 4A10 that target IL-7Rα could represent a meaningful advance for these young patients and their families."

Mechanistic Rationale

4A10 is a highly selective IgG1 monoclonal antibody designed to bind to CD127, which is implicated in T-ALL and pre–B-ALL cell oncogenesis and resistance. Once bound to CD127, the agent induces antibody-dependent cellular cytotoxicity and phagocytosis, leading to targeted elimination of leukemic cells.⁵

This mechanism has demonstrated promising specificity, antileukemic activity, and tolerability in preclinical studies.^5,6 Specifically, results showed a modest reduction in normal peripheral blood T lymphocytes.

Next Steps in Development

The encouraging preclinical data and new fast track designation support the initiation of a phase 1/2a first-in-human trial of 4A10, which will evaluate the safety and preliminary efficacy of the agent in the clinical setting.

In addition to ALL, the sponsor is interested in investigating 4A10 in other hematologic and solid malignancies expressing CD127.

REFERENCES‌

1. Advancing hope for children with leukemia: Allterum Therapeutics receives FDA fast track designation for 4A10 in acute lymphoblastic leukemia. News release. Fannin. November 11, 2025. Accessed November 13, 2025. https://tinyurl.com/y6meu57f

2. Fast track. US Food & Drug Administration. Updated August 13, 2024. Accessed November 13, 2025. https://tinyurl.com/ms2695jn

3. Ding F, Deng L, Xiong J, Cheng Z, Xu J. Analysis of global trends in acute lymphoblastic leukemia in children aged 0-5 years from 1990 to 2021. Front Pediatr. 2025;13:1542649. doi:10.3389/fped.2025.1542649

4. SEER cancer stat facts: acute lymphocytic leukemia. National Cancer Institute. Accessed November 13, 2025. https://tinyurl.com/4zhuhpd2

5. Rodrigues GO, Zenatti PP, Feitoza JM, et al. Abstract 7044: In vitro and in vivo activity of the CD127 monoclonal antibody 4A10 in preclinical models of childhood acute lymphoblastic leukemia. Cancer Res. 2025;85(8 suppl 1):7044. doi:10.1158/1538-7445.am2025-7044

6. Hixon JA, Andrews C, Kashi L, et al. New anti-IL-7Rα monoclonal antibodies show efficacy against T cell acute lymphoblastic leukemia in pre-clinical models. Leukemia. 2020;34(1):35-49. doi:10.1038/s41375-019-0531-8