Clinical trial NCT06325748: SENTI-202: Off-the-shelf Logic Gated CAR NK Cell Therapy in Adults With CD33 and/or FLT3 Blood Cancers Including AML/MDS
Official title: SENTI-202-101: A Phase 1, Multicenter, Open-Label Study of SENTI-202, a Selective Off-the-Shelf Logic Gated CAR NK Cell Therapy, in Subjects With CD33 and/or FLT3 Expressing Malignancies
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
Conditions: AML/MDS
CD33 Expressing Hematological Malignancies
FLT3 Expressing Hematological Malignancies
Keywords: SENTI-202
CAR NK
natural killer cell
CD33
FLT3
allogeneic
logic gate
relapsed/refractory AML
relapsed/refractory MDS
inhibitory CAR
activating CAR
NOT logic gate
IL15
interleukin 15
cell therapy
off-the-shelf
leukemic stem cells
blastic plasmacytoid dendritic cell neoplasm (BPDCN)
multiple myeloma (MM)
mixed phenotype acute leukemia (MPAL)
endomucin
Lead sponsor: Senti Biosciences
Sponsor class: INDUSTRY
First posted: 2024-03-22
Enrollment: 21
Sex: ALL
Minimum age (years): 18
Maximum age (years): 74
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Detailed description: 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/or 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).

Eligibility criteria: 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 outcomes:
measure: Safety and tolerability for dose determination of SENTI-202
timeFrame: At the end of each treatment cycle (each cycle is 28 days) and through study completion, up to 2 years
Secondary outcomes:
measure: Anti-cancer activity of SENTI-202
timeFrame: Through study completion, up to 2 years
measure: Pharmacokinetic (PK) and pharmacodynamic (PDn) profile of SENTI-202
timeFrame: Through study completion, up to 2 years
measure: Host immune response to SENTI-202
timeFrame: Through study completion, up to 2 years
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: UCLA Medical Center
state: California
city: Denver
country: United States
facility: Colorado Blood Cancer Institute
state: Colorado
city: Jacksonville
country: United States
facility: Mayo Clinic
state: Florida
city: Nashville
country: United States
facility: TriStar Bone Marrow Transplant
state: Tennessee
city: Houston
country: United States
facility: MD Anderson Cancer Center
state: Texas
city: San Antonio
country: United States
facility: Methodist Healthcare
state: Texas
city: Camperdown
country: Australia
facility: Royal Prince Alfred Hospital
state: New South Wales
city: Melbourne
country: Australia
facility: Peter MacCallum Cancer Center
state: Victoria
Study officials:
affiliation: Senti Biosciences, Medical Director
name: Rochelle Emery, MD
role: STUDY_DIRECTOR
References: