Investigation of SENTI-202 in R/R AML Continues After Confirming RP2D

After confirming the recommended phase 2 dose (RP2D) of the off-the-shelf CAR natural killer (NK)–cell therapy SENTI-202, a phase 1 study (NCT06325748) is actively enrolling additional patients with relapsed/refractory acute myeloid leukemia (AML) to receive the agent at this dose level.¹

Prior findings from the study supported the RP2D of 1.5 x 10⁹ CAR-positive NK cells administered on days 0, 7, and 14 of a single 28-day treatment cycle. The administration of SENTI-202 follows lymphodepletion comprised of fludarabine and cytarabine.

Preliminary data from the expansion cohort of patients with relapsed/refractory AML are expected to read out before the end of 2025.

“Establishing the RP2D is a pivotal milestone in our clinical development program. This achievement reflects the strength of our preliminary data and positions us to advance into the next phase of development with confidence,” Timothy Lu, MD, PhD, co-founder and chief executive officer of Senti Biosciences, stated in a news release. “We remain focused on the successful execution of the phase 1 trial and, importantly, advance a potential new treatment option for patients with AML, who remain in urgent need of better therapeutic options.”

Prior Phase 1 Data

Findings presented at the 2025 AACR Annual Meeting showed that among patients with relapsed/refractory AML treated during the dose-finding portion of the study (n = 9), no dose-limiting toxicities (DLTs) were reported, and the maximum tolerated dose (MTD) was not reached.² The safety profile of SENTI-202 was consistent with other investigational NK-cell therapies; grade 3 or higher febrile neutropenia and decreased platelet count occurred in 4 patients each, and grade 3 anemia and abdominal pain were both reported in 2 patients. These adverse effects (AEs) were unrelated to SENTI-202 or a result of lymphodepletion. No grade 5 AEs occurred.

In the efficacy-evaluable population (n = 7), 5 patients achieved an overall response, defined as a composite complete response (cCR) or morphologic leukemia-free state. Four patients experienced a cCR, including 3 who had a CR with full hematologic recovery, and 1 patient who had a CR with partial hematologic recovery. In 3 patients treated at the RP2D, 2 achieved a cCR.

All 4 patients who experienced a cCR were minimal residual disease–negative per local assessment. At data cutoff, these 4 patients remained in remission, with the longest follow-up extending past 8 months. Three of these patients underwent a subsequent bone marrow transplant.

Phase 1 Trial Breakdown

The study is enrolling patients 18 to 74 years of age with CD33- and/or FLT3-expressing hematologic malignancies, including patients with relapsed/refractory AML; those with myelodysplastic syndromes (MDS); or patients with other malignancies who have received at least 1 prior line of therapy.³

For patients with AML, morphologic relapse is required, defined as at least 5% bone marrow blasts. At least 1 prior line of therapy is required for patients with AML, but no more than 3 prior lines of standard therapy is permitted. Prior targeted therapy is needed for patients with AML harboring FLT3 or IDH1/2 mutations.

Other key inclusion criteria for all patients comprise an ECOG performance status of 0 or 1, along with adequate organ function and platelet count.

In the dose-finding portion of the trial, patients received SENTI-202 following a lymphodepletion regimen featuring fludarabine and cytarabine. The CAR NK-cell therapy was given as a 3-dose regimen (the RP2D), or as part of a 5-day regimen, with SENTI-202 given on days 0, 3, 7, 10, and 14 of a 28-day cycle. Notably, patients are allowed to receive a maximum of 3 treatment cycles.

Safety, including determining the RP2D and MTD, is the trial’s primary end point. Secondary end points include efficacy, pharmacokinetics/pharmacodynamics, and immune response.

References

1. Senti Bio determines recommended phase 2 dose (RP2D) in phase 1 study of SENTI-202 for the treatment of relapsed/refractory hematologic malignancies, including acute myeloid leukemia. News release. Senti Biosciences. August 5, 2025. Accessed August 5, 2025. https://investors.sentibio.com/news-releases/news-release-details/senti-bio-determines-recommended-phase-2-dose-rp2d-phase-1-study
2. Senti Bio’s SENTI-202, a first-in-class off-the-shelf logic gated selective CD33 or FLT3 not EMCN CAR NK cell therapy, demonstrates positive preliminary clinical results in the treatment of patients with relapsed/refractory AML. News release. Senti Biosciences. April 28, 2025. Accessed August 5, 2025. https://investors.sentibio.com/news-releases/news-release-details/senti-bios-senti-202-first-class-shelf-logic-gated-selective
3. SENTI-202: off-the-shelf logic gated CAR NK cell therapy in adults with CD33 and/​or FLT3 blood cancers including AML/​MDS. ClinicalTrials.gov. Updated March 30, 2025. Accessed August 5, 2025. https://clinicaltrials.gov/study/NCT06325748