FDA Grants Fast Track Designation to CER-1236 in Acute Myeloid Leukemia

The FDA has granted fast track designation to CER-1236, an autologous chimeric engulftment receptor T-cell therapy targeting TIM-4-L, for the treatment of patients with acute myeloid leukemia (AML).1,2

The agent is under evaluation in a first-in-human, multicenter, open-label, phase 1/1b CertainT-1 trial (NCT06834282) in patients with AML.

“These FDA designations are important additional validation with regard to the urgency of the condition as well as the potential that the agency sees in the existing data as submitted,” Chris Ehrlich, CEO of CERo Therapeutics, stated in a news release.1 “Further, these designations help to decrease the potential time to market and provide additional benefits across the FDA process that are expected to prove both medically and financially valuable. We continue to believe that CER-1236 represents a truly novel approach to cancer immunotherapy and are gratified by this regulatory milestone.”

In June 2025, the FDA granted orphan drug designation to CER-1236 for the treatment of patients with AML.3

CER-1236 operates by fusing the external domain of TIM-4 with intracellular domains from T cells and innate immune cells, such as Toll-like receptor 2, CD28, and CD3ζ. The receptor binds TIM-4-ligand on tumor cells, resulting in phagocytosis and death of target cells.2 An adaptive immune response ensues from tumor antigen processing and cross-penetration. Approximately 88% of patients with primary AML will express TIM-4-L, making it a valuable target for therapeutic development. In a preclinical study, CER-1236 eradicated a xenograft model of all AML cells both in vitro and in vivo.

The first-in-human study was designed to establish the safety and preliminary clinical activity of the agent in several populations with high unmet need: patients with relapsed/refractory disease, and those who achieve remission but are left with measurable residual disease (MRD).

The phase 1/1b study enrolled patients aged 18 to 85 years who had received a diagnosis of relapsed/refractory AML; AML in composite complete response (CR) with detectable or persistent or recurrent MRD above 0.1% by multiparametric flow cytometry; or newly diagnosed, TP53-mutated AML, or myelodysplastic syndrome/AML per the International Consensus Classification 2022 criteria eligible for standard of care therapy.

Patients were excluded if they received prior therapy with a permanently integrated, genetically modified cell product, cytotoxic chemotherapy, targeted therapy, antibody-drug conjugate, radiation therapy, immunotherapy, or other investigational therapy within 2 weeks of 5 half-lives before leukapheresis. Additional exclusion criteria included a white blood cell count above 10 x 109/L or peripheral bone marrow blasts above 30%, active and uncontrolled congestive heart failure, and acute promyelocytic leukemia with translocation (t)15;17, or t11;17(q23;q21).

In phase 1, patients started on a dose of 1 x 106 cells/kg and were either de-escalated to 0.3 x 106 cells/kg or 2.0 x 106 cells/kg, and if tolerated, 5 x 106 cells/kg. In part 2, patients were grouped into 3 cohorts: relapsed/refractory, MRD-positive CR, or TP53-mutant disease.

Per the trial protocol, patients underwent screening followed by leukapheresis, bridging therapy, and lymphodepletion with 30 mg/m2 of fludarabine per day and 400 mg/m2 of cyclophosphamide per day for 3 days before receiving a single cell infusion 2 days later. Post-treatment bone marrow assessments were performed on day +28 and +42.

The primary objective part 1 of the study was to establish the safety of the agent through dose-limiting toxicity, treatment-emergent adverse effects (AEs), cytokine release syndrome, immune effector cell–associated neurotoxicity syndrome, and AEs of interest. Part 2 will focus on estimating the objective response rate by CR, CR with partial hematologic recovery, and CR with incomplete hematologic recovery, and MRD negativity by flow cytometry.

In May 2025, the developer of the agent CERo Therapeutics announced that the first patient had been dosed in the trial.4

References

1. CERo Therapeutics receives FDA fast track designation for CER-1236 in acute myeloid leukemia. News release. CERo Therapeutics. September 5, 2025. Accessed September 5, 2025. https://www.cero.bio/press-release?storyId=6780690611361163
2. Maiti A, Ramdial JL, Cieniewicz B, et al. First-in-human study of autologous chimeric engulfment receptor T-cell CER-1236 targeting TIM-4-l in acute myeloid leukemia (CertainT-1). J Clin Oncol. 2025;43(16):TPS6581. doi:10.1200/JCO.2025.43.16_suppl.TPS658
3. CERo Therapeutics Holdings, Inc. announces FDA orphan drug designation granted to CER-1236 for the treatment of acute myeloid leukemia (AML). News release. CERo Therapeutics. June 17, 2025. Accessed September 5, 2025. https://cero.bio/press-release?storyId=7477275225065985
4. CERo Therapeutics Holdings, Inc. doses first patient with CER-1236 in phase 1 clinical trial for acute myeloid leukemia and is advancing through protocol-defined evaluations. News release. CERo Therapeutics. May 30, 2025. Accessed September 5, 2025. https://www.cero.bio/press-release?storyId=6336586559646417