By: Kerri Fitzgerald
A study presented at the American Association for Cancer Research Annual Meeting 2025 found that the investigational chimeric antigen receptor (CAR) therapy SENTI-202 induced complete remission in patients with relapsed or refractory acute myeloid leukemia (AML).
The first-in-class, off-the-shelf CAR natural killer (NK) cell therapy uses a logic-gating design targeting CD33 and FLT3.
At the January 2025 data cutoff in the ongoing, multicenter, phase 1 study, nine patients with relapsed or refractory AML have received at least one cycle of SENTI-202. No dose-limiting toxicities were observed, and the maximum-tolerated dose was not reached. The preliminary phase 2 recommended dose was three doses of 1.5 billion cells per cycle.
Seven patients were evaluable for response, four of whom experienced complete remission (CR) with no evidence of measurable residual disease. All CRs were ongoing after a maximum follow-up of more than eight months.
Patients reported grade 3 or higher febrile neutropenia (n=4) and decreased platelet count. Grade 3 anemia and abdominal pain were also reported (n=2 each).
“There are very few ‘clean’ cancer targets that are only expressed on cancer cells but not on healthy cells,” said the lead author Stephen A. Strickland, MD, of SCRI at TriStar Bone Marrow Transplant, in a press release. “The logic-gating technology potentially solves this issue by recognizing one or more cancer targets to trigger deeper cancer killing while recognizing healthy cells to prevent them from being affected.”
The study is limited by its small sample size and short follow-up. Studies of SENTI-202 are ongoing.
The study was funded by Senti Biosciences, Inc.
Reference
Strickland SA, Eghtedar A, Farhadfar N, et al. First-in-human, multicenter study of SENTI-202, a CD33/FLT3 selective off-the-shelf logic gated CAR NK cell therapy in hematologic malignancies including AML: clinical data. Abstract #CT014. Presented at the American Association for Cancer Research Annual Meeting 2025; April 25-30, 2025; Chicago, IL.
