Cullinan Therapeutics Reports Promising 30% Response Rate for CLN-049 T Cell Engager in Relapsed AML Patients
核心洞察
Cullinan Therapeutics' CLN-049, a novel FLT3xCD3 bispecific T cell engager, demonstrated a ~30% composite complete response rate in heavily pretreated patients with relapsed/refractory acute myeloid leukemia.
The therapy showed anti-leukemic activity regardless of FLT3 (搜索) mutational status, with responses observed even in patients with poor-prognosis TP53 (搜索)-mutated AML at the highest dose level.
Initial safety data from 40 patients indicated a manageable profile with cytokine release syndrome limited to Grade 1 or 2, and no treatment discontinuations due to immune-related adverse events.
Cullinan Therapeutics has reported encouraging Phase 1 clinical data for CLN-049, a novel FLT3xCD3 bispecific T cell engager, demonstrating approximately 30% composite complete response rates in heavily pretreated patients with relapsed/refractory acute myeloid leukemia (AML). The company will present updated results at the 67th American Society of Hematology Annual Meeting in December 2025.
Clinical Efficacy Demonstrates Broad Therapeutic Potential
As of the June 2025 data cutoff, CLN-049 achieved promising anti-leukemic activity across a diverse patient population. In the 23 AML patients treated at target doses ≥6 μg/kg, the therapy demonstrated a composite complete response (CRc) rate of 30% and an overall response rate of 57%. At the highest target dose studied of 12 μg/kg, 13 patients achieved a CRc rate of 31% and an overall response rate of 69%.
"CLN-049 has the potential to be widely applicable to a broad population because it targets the extracellular domain of both mutated and non-mutated FLT3 (搜索), expressed on malignant blasts in more than 80% of patients with AML," said Mohammad Maher Abdul Hay, MD, Director of the Clinical Leukemia Program at Perlmutter Cancer Center and Director of Blood & Marrow Transplantation and Cellular Therapy Program at NYU Langone Health.
The therapy showed activity regardless of baseline genetic risk factors. Notably, among five patients with TP53 (搜索)-mutated AML treated at 12 μg/kg—a population with particularly poor prognosis—four responses were observed, including two complete responses with hematologic recovery and two morphologic leukemia-free states.
Manageable Safety Profile Supports Continued Development
The Phase 1 study enrolled 40 patients (34 AML, 6 MDS) across seven dose cohorts ranging from 1.5-12 μg/kg target doses. Patients with AML had received a median of two prior therapies, with some having received up to eight previous treatments.
Safety data indicated a manageable profile across all doses assessed. The most common treatment-emergent adverse events included cytokine release syndrome (40%), infusion-related reaction (35%), and febrile neutropenia, pneumonia, stomatitis, and white blood cell count decrease (17.5% each). All cytokine release syndrome events were limited to Grade 1 or 2, with the majority occurring after step-up dosing or the first target dose. One case of Grade 1 immune effector cell-associated neurotoxicity syndrome was reported in association with Grade 2 cytokine release syndrome. Neither adverse event led to treatment discontinuation.
Addressing Critical Unmet Medical Need in AML
"AML is among the largest hematology indications for which a T cell engager is not available, so we are pleased to share new data for CLN-049 that demonstrate compelling potential for patients with relapsed or refractory AML, a population that urgently needs new treatment options," said Jeffrey Jones, MD, MBA, Chief Medical Officer at Cullinan Therapeutics.
AML affects approximately 22,000 people annually in the United States, with about 11,000 deaths each year. Globally, the disease impacts an estimated 144,000 people annually, resulting in approximately 130,000 deaths. Despite recent therapeutic advances, outcomes remain poor, particularly for patients with relapsed or refractory disease, where five-year survival rates are 10% or less.
Mechanism of Action and Clinical Development
CLN-049 is designed as a bispecific antibody that simultaneously binds to FLT3 (搜索) on leukemia cells and CD3 (搜索) on T cells, redirecting the patient's immune system to attack cancer cells. The therapy's ability to target both mutated and non-mutated FLT3 makes it potentially applicable to a broad AML patient population, as FLT3 is expressed on malignant blasts in more than 80% of AML cases.
The ongoing Phase 1 study continues dose escalation, with 29 AML patients currently efficacy evaluable. Among nine patients achieving bone marrow blasts below 5%, 33% were minimal residual disease-negative by flow cytometry, with no relapses observed in this subset. One patient has remained on study for more than six months.
Strategic Portfolio Focus and Financial Position
The CLN-049 program represents part of Cullinan's strategic focus on T cell engagers applied to well-validated targets. The company recently discontinued development of CLN-619 and CLN-617 programs following review of emerging clinical data, allowing concentration of resources on higher-conviction programs.
Cullinan reported cash, cash equivalents, and investments of $475.5 million as of September 30, 2025, providing an expected runway into 2029 under the company's current operating plan. The focused pipeline approach is designed to deliver meaningful value-driving catalysts across programs in 2026 and beyond.
The company will host an in-person investor event on December 8, 2025, featuring discussion of the CLN-049 data with David Sallman, MD, Associate Member and Myeloid Section Head at Moffitt Cancer Center & Research Institute, alongside Cullinan management.