Clinical Trial Finder

Inclusion Criteria:

• - Subjects with CD33 and/or FLT3 expressing malignancies, including: - Relapsed refractory acute myeloid leukemia (AML) with morphologic relapse as defined by ≥5% bone marrow blasts who have received at least 1 prior line, but no more than 3 prior lines of standard anti-AML therapy.

Subjects with FLT3-mutated or IDH ½-mutated disease must have received at least one prior targeted therapy.

• - Relapsed refractory myelodysplastic syndrome (MDS) with increased blasts who have received at least 1 prior line, but no more than 2 prior lines of anti-MDS therapy.

• - Other hematological malignancies who have received at least 1 prior line of standard of care for the respective disease.

• - Documentation of CD33 expression (or FLT3 expression if available) by individual institutional standard of care.

• - ECOG performance score of 0-1.

• - Adequate organ function including platelet count >20x109/L (platelet transfusion is permitted) - Adequate recovery from toxicities from previous cancer treatments, as described in the study protocol.

• - Willing and able to provide written informed consent.

Exclusion Criteria:

• - White blood cell (WBC) count of ≥20×109/L or circulating blasts ≥10×109/L or rapidly progressive/hyperproliferative disease.

• - Acute promyelocytic leukemia with t(15;17) (q22;q12) or abnormal promyelocytic leukemia/retinoic acid receptor alpha (APML-RARA) - MDS with fibrosis (MDS-f) or known prior history of constitutional conditions/syndromes with chemo-responsive AML.

• - Evidence of leukemic meningitis or known active central nervous system disease.

• - Presence of extra-medullary disease or myeloid sarcoma alone with no morphologic hematologic relapse.

• - Prior use of certain anti-cancer therapies and/or use within a certain number of days prior to SENTI-202 study treatment, as described in the study protocol.

• - Hematopoietic cell transplantation (HCT) less than 100 days prior to the first dose of SENTI-202.

• - Prior NK cell or CAR T cell therapy at any time.

• - Prior donor lymphocyte infusion (DLI), except if after HCT for MRD+ disease.

• - Medical conditions or medications prohibited by the study protocol.

- Pregnant or breastfeeding female

This is a dose-finding study of SENTI-202, comprised of an initial dose finding using a modified "3+3" study design to determine the maximum tolerated dose (MTD) and recommended phase two dose (RP2D) of SENTI-202 when administered after lymphodepleting chemotherapy (Part 1) followed by disease-specific expansion cohorts at the RP2D (Part 2).

Arms

Experimental: SENTI-202 CAR NK cell therapy

Part 1 Dose Finding: Sequential cohorts will receive doses of SENTI-202 using a modified 3+3 study design to determine the recommended phase 2 dose (RP2D). The starting dose will be 1 billion cells. Other doses may be explored depending on study data. Part 2 Cohort Expansion: After determination of the RP2D, additional subjects will be enrolled in disease-specific expansion cohorts at that dose to further explore safety, biodynamics, and anti-cancer activity of SENTI-202

Interventions

Biological: - SENTI-202

SENTI-202 is an investigational off-the-shelf CAR NK cell therapy designed to selectively target and eliminate CD33 and/or FLT3 expressing hematological malignancies while sparing healthy cells using a NOT logic gate. 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 (flu/Ara-C). Subjects will receive a minimum of 1 and maximum of 3 treatment cycles.