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

NCT06325748 | Active Not Recruiting Phase 1 FDA Drug

• 1 other identifier: SENTI-202-101
• Study Type: interventional
• Target: 21
• Locations: 2 countries
• Sites: 8

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.

Conditions

FLT3 Expressing Hematological Malignancies; AML/MDS; CD33 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

Outcome Measures

Primary Outcomes (2)

• Safety and tolerability for dose determination of SENTI-202

  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

  At the end of each treatment cycle (each cycle is 28 days) and through study completion, up to 2 years

• For subjects enrolled in the Dose Expansion Cohort(s): Anti-cancer activity of SENTI-202

  The response rate to SENTI-202 will be measured using clinical measures of benefit as defined by standard consensus criteria for the respective disease

  Through study completion, up to 2 years

Secondary Outcomes (3)

• For subjects enrolled in the Dose Finding Cohorts: Anti-cancer activity of SENTI-202

  Through study completion, up to 2 years

• Pharmacokinetic (PK) and pharmacodynamic (PDn) profile of SENTI-202

  Through study completion, up to 2 years

• Host immune response to SENTI-202

  Through study completion, up to 2 years

Study Arms (1)

SENTI-202 CAR NK cell therapy

EXPERIMENTAL

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

Biological: SENTI-202

Interventions

SENTI-202 BIOLOGICAL

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.

Also known as: Fludarabine, Cytarabine (ara-C)

SENTI-202 CAR NK cell therapy

Eligibility Criteria

• Age: 18 Years - 74 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Senti Biosciences: lead

Study Sites (8)

UCLA Medical Center

Los Angeles, California, 90095, United States

Location

Colorado Blood Cancer Institute

Denver, Colorado, 80218, United States

Location

Mayo Clinic

Jacksonville, Florida, 32224, United States

Location

TriStar Bone Marrow Transplant

Nashville, Tennessee, 37203, United States

Location

MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Methodist Healthcare

San Antonio, Texas, 78229, United States

Location

Royal Prince Alfred Hospital

Camperdown, New South Wales, 2050, Australia

Location

Peter MacCallum Cancer Center

Melbourne, Victoria, 3000, Australia

Location

MeSH Terms

Conditions

Leukemia, Myeloid, Acute; Recurrence; Blastic Plasmacytoid Dendritic Cell Neoplasm; Multiple Myeloma; Leukemia, Biphenotypic, Acute

Interventions

fludarabine; Cytarabine

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Histiocytic Disorders, Malignant; Lymphoma; Hematologic Neoplasms; Neoplasms by Site; Skin Neoplasms; Skin Diseases; Skin and Connective Tissue Diseases; Neoplasms, Plasma Cell; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hemorrhagic Disorders; Lymphoproliferative Disorders; Immunoproliferative Disorders; Immune System Diseases; Leukemia, Lymphoid; Lymphatic Diseases

Intervention Hierarchy (Ancestors)

Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Arabinonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides

Study Officials

• Rochelle Emery, MD

  Senti Biosciences, Medical Director

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 13, 2024
• First Posted: March 22, 2024
• Study Start: April 22, 2024
• Primary Completion: February 1, 2026
• Study Completion (Estimated): August 1, 2040
• Last Updated: February 12, 2026

Record last verified: 2026-02

Locations

US (6); AU (2)