FDA Grants Fast Track Designation to 4A10 for Relapsed/Refractory Acute Lymphoblastic Leukemia

The FDA has granted Fast Track designation to 4A10, an investigational monoclonal antibody targeting interleukin-7 receptor alpha (IL-7Rα; CD127), for the treatment of patients with relapsed or refractory acute lymphoblastic leukemia (ALL).

4A10 is a human IgG1 monoclonal antibody engineered to selectively bind CD127, a critical component of both the IL-7 receptor and the thymic stromal lymphopoietin receptor (TSLPR), which are expressed on T-ALL and pre-B-ALL cells, respectively. By blocking IL-7–driven signaling and promoting antibody-dependent cellular cytotoxicity and phagocytosis, 4A10 is designed to directly target and eliminate leukemic cells across multiple ALL subtypes. The Fast Track designation underscores the potential clinical importance of this therapy as it advances through development.

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

The fast track designation follows the recent FDA clearance of Allterum’s investigational new drug (IND) application, enabling the company to advance 4A10 into a phase 1 first-in-human clinical trial for patients with relapsed or refractory ALL.

What preclinical data supported the fast-track designation for 4A10 for relapsed/refractory ALL?

Preclinical studies of 4A10, a monoclonal antibody directed against CD127, demonstrated broad antileukemic activity across multiple B-cell acute lymphoblastic leukemia (B-ALL) genetic subtypes, supporting further clinical development of this agent for relapsed or refractory disease.

Investigators first confirmed high CD127 expression across six major B-ALL genetic subtypes, establishing a strong biologic rationale for targeting the interleukin-7 receptor alpha chain. In vitro assays showed potent 4A10-mediated antibody-dependent cellular cytotoxicity (ADCC) against multiple CD127-expressing cell lines, including KOPN8, REH, and NALM6.

In vivo, 4A10 monotherapy produced robust suppression of leukemia proliferation and significantly prolonged survival across a diverse panel of patient-derived xenograft (PDX) models. Activity was observed in CRLF2-rearranged Ph-like and Down syndrome–associated B-ALL, as well as in BCR::ABL1, TCF3::PBX1, ETV6::RUNX1, and high-hyperdiploid leukemias. In steroid-resistant KOPN8 xenografts, 4A10 demonstrated meaningful antitumor activity as a single agent, with further enhancement seen when combined with dexamethasone.

“Children and young adults with relapsed ALL confront daunting odds and a profound lack of effective options,” Yan Moore, MD, chief executive officer of Allterum, shared in the news release. “The FDA’s fast track designation for 4A10 affirms its potential and empowers us to work hand-in-hand with the agency to bring this therapy to patients and families as quickly as possible.”

Investigators noted that these findings support CD127 as a promising therapeutic target and provide a compelling rationale for advancing 4A10 into early-phase clinical development for pediatric ALL.

“Fast track designation brings us another step closer to delivering 4A10 to patients who need it most,"”Atul Varadhachary, MD, PhD, executive chair of Allterum and Fannin Managing Partner, added in the news release. “This recognition validates the strength of our CD127 platform and the science behind 4A10, reinforcing our mission to change outcomes for children and adults with ALL and related cancers.”

References

1. Advancing hope for children with leukemia: Allterum Therapeutics receives FDA fast track designation for 4A10 in acute lymphoblastic leukemia. Allterum Therapeutics. News Release. November 11, 2025. Accessed November 13, 2025. file:///Users/jdieugenio/Downloads/Allterum_PR_FastTrack_11_11_25.pdf
2. Rodrigues GO, Zenatti PP, Feitoza JM, et al. In vitro and in vivo activity of the CD127 monoclonal antibody 4A10 in preclinical models of childhood acute lymphoblastic leukemia. Presented at: AACR Annual Meeting 2025; April 25-30, 2025; Chicago, IL. Abstract 7044 https://aacrjournals.org/cancerres/article/85/8_Supplement_1/7044/760473/Abstract-7044-In-vitro-and-in-vivo-activity-of-the