Switching from a one-step to a two-step dosing ramp cut the cytokine release syndrome rate in Cullinan Therapeutics’ CLN-049 trial from 36% down to 26%, and eliminated Grade 3 CRS events entirely in patients who received the adjusted regimen. That safety signal matters because it came alongside the strongest efficacy numbers the program has posted: at the 12 µg/kg target dose, patients who started on a step-up of 1.5 µg/kg or lower hit a 53% overall response rate and a 26% complete remission composite rate, figures Cullinan will present in full at the 68th ASH Annual Meeting in December.
The dataset now covers 87 patients across 13 cohorts, with 80 assessed for efficacy. CLN-049 is a FLT3xCD3 bispecific T-cell engager, a mechanistic category distinct from CAR-T, targeting FLT3-expressing blasts in relapsed or refractory AML and MDS. Transaminase elevations had been a concern at 14% overall for Grade 3 or worse events, but the two-step regimen brought that down to 4% (1 of 27 patients), and the elevations recorded were asymptomatic and reversible. Neurological toxicity remained modest: immune effector cell-associated neurotoxicity occurred in 6% of all patients, with one Grade 3 event, and all events were self-limiting.
The durability signals in a small subset are worth watching. Two patients stayed on CLN-049 beyond 12 months without additional consolidation therapy, and four others used responses as a bridge to allogeneic stem cell transplantation. Five patients achieved measurable residual disease-negative responses by multiparameter flow cytometry. None of this constitutes a registration-ready dataset, but it gives the Phase 2 trial a clearer dosing anchor:. The relapsed or refractory AML space has seen approvals such as revumenib for KMT2A-rearranged and NPM1-mutated disease, but those are mutation-specific; CLN-049’s FLT3-directed approach targets a different subset, and the Phase 2 data will need to show whether the 53% ORR at the optimal dose holds in a less heterogeneous cohort.
The number to track when Phase 2 reads out is the CRc rate at 12 µg/kg in patients selected for lower step-up dosing. At 26% in 19 patients, it is promising but statistically thin; a Phase 2 confirmation in a larger, more uniform group is what converts this Phase 1 signal into a development decision.
Source link: https://www.sec.gov/Archives/edgar/data/1789972/000119312526446348/cgem-20261104.htm
Jon Napitupulu is Director of Media Relations at The Clinical Trial Vanguard. Jon, a computer data scientist, focuses on the latest clinical trial industry news and trends.
