The fast track designation is supported by data from a phase 1 trial (NCT05143996), which evaluated the novel FLT3 x CD3 bispecific T-cell engager in patients with relapsed or refractory AML or myelodysplastic syndrome (MDS). At the June 2025 data cutoff date, top-line results from the study demonstrated that patients with AML who received CLN-049 at a target dose of at least 6 μg/kg (n = 23) experienced an overall response rate (ORR) of 57% and a composite complete response (CRc) rate of 30%.2 Patients with AML or MDS who received the agent at the highest target dose of 12 μg/kg (n = 13) experienced an ORR of 69% and a CRc rate of 31%. Additional data from the trial will be presented during the 2025 ASH Annual Meeting in an oral presentation on December 8.1
“Fast track designation underscores both the urgent need for new options in relapsed and refractory AML and the promise of CLN-049,” Jeffrey Jones, MD, MBA, chief medical officer of Cullinan Therapeutics—the developer of CLN-049—stated in a news release. “Initial results from our phase 1 study have shown meaningful efficacy, including CRs, reinforcing the broad potential of this FLT3-directed T-cell engager in a population where effective treatment options are currently limited and fragmented. 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.”
What were the key design characteristics of the phase 1 study of CLN-049 in AML and MDS?
The phase 1 open-label, multicenter, first-in-human trial of CLN-049 enrolled patients with relapsed or refractory AML or MDS who were at least 18 years of age.3 Other key inclusion criteria included a white blood cell (WBC) count at the time of first dose of less than 20,000/μL, an ECOG performance status of 0 to 2, and adequate laboratory values. Additionally, toxicities related to prior study therapy should have resolved to grade 1 severity or less, excluding alopecia, lymphopenia, neutropenia, leukopenia, anemia, and thrombocytopenia.
During part A of the study, intravenous (IV) CLN-049 was administered in single ascending doses. In parts B and C, the agent was given in multiple ascending doses via IV and subcutaneous dosing, respectively.
The primary end points were safety and pharmacokinetic measures. The immunogenicity of CLN-049 was assessed as a secondary end point.
What is currently known about the safety profile of CLN-049?
Preliminary safety data from the phase 1 trial of CLN-049 showed that the agent displayed a manageable safety profile in patients with relapsed/refractory AML or MDS (n = 40).2 The most common any-grade treatment-emergent adverse effects (TEAEs) included cytokine release syndrome (CRS; 40%), infusion-related reactions (35%), febrile neutropenia (17.5%), pneumonia (17.5%), stomatitis (17.5%), and decreased WBC count (17.5%). All instances of CRS were grade 1 or 2, and there was 1 case of grade 1 immune effector cell–associated neurotoxicity syndrome (ICANS) that was reported in association with grade 2 CRS. Treatment discontinuation did not occur due to CRS or ICANS. Grade 3 or higher TEAEs that occurred in more than 10% of patients included febrile neutropenia (17.5%), decreased WBC count (17.5%), and pneumonia (12.5%).
References
- 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. December 1, 2025. Accessed December 1, 2025. https://investors.cullinantherapeutics.com/news-releases/news-release-details/cullinan-therapeutics-receives-fda-fast-track-designation-cln
- Cullinan Therapeutics to showcase new data demonstrating compelling clinical activity for CLN-049, a novel FLT3xCD3 T cell engager, in AML patients in an oral presentation at the 67th ASH Annual Meeting. News release. Cullinan Therapeutics. November 3, 2025. Accessed December 1, 2025. https://investors.cullinantherapeutics.com/node/9651/pdf
- CLN-049 in patients with relapsed/refractory acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS). ClinicalTrials.gov. Updated November 11, 2025. Accessed December 1, 2025. https://clinicaltrials.gov/study/NCT05143996
