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 either a 3 dose regimen (Schedule 1: Days 0, 7, 14) or a 5 dose regimen (Schedule 2: Days 0, 3, 7, 10, 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 to achieve optimal response with the optionality of an additional consolidation cycle thereafter. Additional dosing schedules may be explored depending on study data.
Study 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.
Eligibility
Sex
ALL
Min age
18 Years
Max age
74 Years
Healthy volunteers
No
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
Primary outcome measure(s)
Safety and tolerability for dose determination of SENTI-202 — At the end of each treatment cycle (each cycle is 28 days) and through study completion, up to 2 years Incidence, type, frequency, and severity of adverse events and dose limiting toxicities will be assessed to determine the maximum tolerated dose and/or recommended phase 2 dose and dosing regimen
For subjects enrolled in the Dose Expansion Cohort(s): Anti-cancer activity of SENTI-202 — Through study completion, up to 2 years The response rate to SENTI-202 will be measured using clinical measures of benefit as defined by standard consensus criteria for the respective disease
Trial sites (8)
Facility
City
Region
Status
UCLA Medical Center
Los Angeles
California
Colorado Blood Cancer Institute
Denver
Colorado
Mayo Clinic
Jacksonville
Florida
TriStar Bone Marrow Transplant
Nashville
Tennessee
MD Anderson Cancer Center
Houston
Texas
Methodist Healthcare
San Antonio
Texas
Royal Prince Alfred Hospital
Camperdown
New South Wales
Peter MacCallum Cancer Center
Melbourne
Victoria
Official registry record
This page summarises publicly available registry data for informational purposes — not medical advice. Eligibility is determined by each study team; patients should discuss participation with their clinician.
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