SENTI-202: Off-the-shelf Logic Gated CAR NK Cell Therapy in Adults with CD33 And/or FLT3 Blood Cancers Including AML/MDS
- Conditions
- AML/MDSCD33 Expressing Hematological MalignanciesFLT3 Expressing Hematological Malignancies
- Interventions
- Biological: SENTI-202
- Registration Number
- NCT06325748
- Lead Sponsor
- Senti Biosciences
- 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).
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 21
-
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
- 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description SENTI-202 CAR NK cell therapy SENTI-202 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 SENTI-202 CAR NK cell therapy SENTI-202 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
- Primary Outcome Measures
Name Time Method 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
- Secondary Outcome Measures
Name Time Method 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
Pharmacokinetic (PK) and pharmacodynamic (PDn) profile of SENTI-202 Through study completion, up to 2 years Levels of circulating SENTI-202 and peripheral cytokine levels will be measured to assess the PK/PDn profile of SENTI-202
Host immune response to SENTI-202 Through study completion, up to 2 years Anti-SENTI-202 immune response and RCR will be measured in blood samples
Trial Locations
- Locations (8)
UCLA Medical Center
🇺🇸Los Angeles, California, United States
Colorado Blood Cancer Institute
🇺🇸Denver, Colorado, United States
Mayo Clinic
🇺🇸Jacksonville, Florida, United States
TriStar Bone Marrow Transplant
🇺🇸Nashville, Tennessee, United States
MD Anderson Cancer Center
🇺🇸Houston, Texas, United States
Methodist Healthcare
🇺🇸San Antonio, Texas, United States
Royal Prince Alfred Hospital
🇦🇺Camperdown, New South Wales, Australia
Peter MacCallum Cancer Center
🇦🇺Melbourne, Victoria, Australia