FDA Grants Fast Track Designation to Novel FLT3/CD3 Bispecific in R/R AML

Investigators are currently evaluating the safety, tolerability, pharmacokinetics, pharmacodynamics, and preliminary activity of CLN-049 among patients with relapsed/refractory AML or MDS as part of an open-label phase 1 trial (NCT05143996).

CLN-049, an investigational FLT3/CD3 bispecific T-cell engager, has received fast track designation from the FDA as a treatment for those with relapsed/refractory acute myeloid leukemia (AML), according to a news release from the developer, Cullinan Therapeutics, Inc.1

Developers engineered CLN-049 to attack FLT3-expressing leukemia cells as a potential therapeutic strategy for patients with AML and myelodysplastic syndrome (MDS). Investigators hypothesize that the agent may have wide clinical application across a broad patient population based on its ability to target both mutated and non-mutated FLT3.

Investigators are currently evaluating the safety, tolerability, pharmacokinetics, pharmacodynamics, and preliminary activity of CLN-049 among patients with relapsed/refractory AML or MDS as part of an open-label phase 1 trial (NCT05143996). Findings from the phase 1 study are slated for presentation at the upcoming 2025 American Society of Hematology (ASH) Annual Meeting and Exposition.

“Fast track designation underscores both the urgent need for new options in relapsed and refractory acute myeloid leukemia and the promise of CLN-049. Initial results from our Phase 1 study have shown meaningful efficacy, including complete responses, reinforcing the broad potential of this FLT3-directed T-cell engager in a population where effective treatment options are currently limited and fragmented,” Jeffrey Jones, MD, MBA, chief medical officer at Cullinan Therapeutics, stated in the news release.1 “This regulatory milestone provides important momentum for development, and we look forward to collaborating closely with the FDA to rapidly advance CLN-049 for patients who desperately need more effective therapies.”

Investigators of the phase 1 study are assessing CLN-049 across 3 parts.2 Part A of the trial will evaluate the agent at a single ascending dose; patients will receive treatment as a single intravenous infusion. In part B, patients will receive multiple ascending doses of the agent every 7 days following an initial lead-in intravenous dose. In part C, patients will receive multiple ascending doses of the agent every 7 days via subcutaneous injection.

The trial’s primary end points include the incidence of treatment-emergent adverse effects (TEAEs), the maximum drug concentration, the observed plasma concentration of a dosing interval, and the time to maximum drug concentration. The immunogenicity of CLN-049 based on the number of positive anti-drug antibody samples at the end of therapy minus the number of positive samples at baseline will be a secondary end point.

Patients 18 years and older with a confirmed diagnosis of relapsed/refractory AML or MDS, progression or recurrence on prior approved therapeutic options, and a baseline white blood cell count under 20,000/uL are eligible for enrollment on the trial. Other eligibility criteria include having an ECOG performance status of 0 to 2 and adequate laboratory values. Those with AEs associated with prior therapies must have their toxicities resolve to grade 1 or less per CTCAE v5.0 guidelines.

Those with acute promyelocytic leukemia, active central nervous system leukemia, isolated extramedullary relapse, or prior organ allograft are ineligible for study entry. Patients are also ineligible for enrollment on the trial if they have concomitant second malignancies requiring active therapy within 12 months of study entrance, active autoimmune disease or a history of known or suspected autoimmune disease, active uncontrolled infection within 7 days of initiating treatment with CLN-049, positivity for HIV 1/2, or receipt of live virus vaccines within 28 days of beginning the study treatment.

According to the news release, investigators are also evaluating treatment with CLN-049 among patients with AML and measurable residual disease as part of a parallel, open-label phase 1 study (EUCT 2023-506572-27-00).

References

1. Cullinan Therapeutics receives FDA fast track designation for CLN-049, a novel FLT3xCD3 T cell engager, in relapsed/refractory acute myeloid leukemia. News release. Cullinan Therapeutics, Inc. December 1, 2025. Accessed December 1, 2025. https://tinyurl.com/4t9mtw5a
2. CLN-049 in patients with relapsed/​refractory acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS). ClinicalTrials.gov. Updated November 25, 2025. Accessed December 1, 2025. https://tinyurl.com/yudzvehv