Senti Biosciences, Inc. (Nasdaq: SNTI) reported positive initial clinical data from its Phase 1 clinical trial of SENTI-202, a Logic Gated off-the-shelf chimeric antigen receptor natural killer (CAR-NK) cell therapy, for relapsed/refractory (R/R) hematologic malignancies, including acute myeloid leukemia (AML). The data, with a cutoff date of September 19, 2024, showed promising early responses and a manageable safety profile in the first three patients treated at the lowest dose level.
Initial Clinical Results
The Phase 1 trial enrolled three patients with R/R AML who received 1.0 billion CAR+ NK cells per dose of SENTI-202, administered three times over a 28-day cycle following lymphodepletion with fludarabine and cytarabine. According to the company, two of the three patients achieved complete remission (CR), confirmed by bone marrow biopsy, indicating blast reduction and recovery of blood cells to normal ranges. Both patients also achieved measurable residual disease (MRD) negativity, defined as no detectable cancer cells in bone marrow samples. As of the report, both patients continued to maintain their remission for over three months.
Safety and Tolerability
SENTI-202 was generally well-tolerated in all three patients, with an adverse event profile consistent with the use of lymphodepleting chemotherapy in patients with AML. There were no dose-limiting toxicities (DLTs) reported. Adverse events included Grade 4 hematologic toxicities (thrombocytopenia, neutropenia & leukopenia, and pancytopenia) and Grade 1 or 2 fevers, with some cases of bacteremia and upper respiratory infection.
Expert Commentary
"R/R AML is a devastating disease that progresses rapidly with no approved therapies once it has progressed past first-line intensive or venetoclax-based treatment," said Kanya Rajangam, MD, PhD, President, Head of R&D and Chief Medical Officer of Senti Bio. "In the trial, early and deep responses at the first dose level were observed along with a generally well-tolerated preliminary safety profile, which is very encouraging."
Stephen A. Strickland, Jr., MD, MSCI, Director, Leukemia Research for Sarah Cannon Research Institute, added, "These early clinical results suggest that SENTI-202 may potentially address the critical limitations of existing therapies and provide hope to people living with AML."
SENTI-202: A Novel Approach
SENTI-202 is designed to selectively target and eliminate CD33 and/or FLT3-expressing hematologic malignancies, including AML, while sparing healthy bone marrow cells. The therapy incorporates an OR GATE, targeting either CD33 or FLT3 to kill leukemic blasts and stem cells, and a NOT GATE, designed to protect healthy cells. It also includes calibrated-release IL-15 to enhance cell persistence and activity.
Next Steps
The Safety Review Committee has cleared the lowest dose cohort, and dose escalation is ongoing at the 1.5 billion CAR+ NK cells/dose level. Senti Bio expects to enroll approximately 20 patients in the Phase 1 trial and anticipates reporting additional safety and efficacy data, including initial durability data, in 2025.
About the Trial
The Phase 1 clinical trial of SENTI-202 (NCT06325748) is enrolling adult patients with R/R CD33 and/or FLT3 expressing hematologic malignancies, including AML, across multiple sites in the United States and Australia. SENTI-202 is administered in 3 weekly doses (Days 0, 7, 14) of a 28-day treatment cycle following a lymphodepletion conditioning regimen of fludarabine and cytarabine. The trial is funded in part by the California Institute for Regenerative Medicine (CIRM).
