SENTI-202: Off-the-shelf Logic Gated CAR NK Cell Therapy in Adults With CD33 and/or FLT3 Blood Cancers Including AML/MDS

About

Brief Summary

This is an open-label study of the safety, biodynamics, and anti-cancer activity of SENTI-202 (an off-the-shelf logic gated CAR NK cell therapy) in patients with CD33 and/or FLT3 expressing blood cancers, including AML and MDS.

Primary Purpose

Treatment

Study Type

Interventional

Phase

Phase 1

Eligibility

Gender

All

Healthy Volunteers

No

Minimum Age

18 Years

Maximum Age

74 Years

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