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

February 10, 2026 updated by: Senti Biosciences

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

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.

Study Overview

Status

Active, not recruiting

Conditions

Intervention / Treatment

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).

Study Type

Interventional

Enrollment (Estimated)

21

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Australia
    • New South Wales
      • Camperdown, New South Wales, Australia, 2050
        • Royal Prince Alfred Hospital
    • Victoria
      • Melbourne, Victoria, Australia, 3000
        • Peter MacCallum Cancer Center
  • United States
    • California
      • Los Angeles, California, United States, 90095
        • UCLA Medical Center
    • Colorado
      • Denver, Colorado, United States, 80218
        • Colorado Blood Cancer Institute
    • Florida
      • Jacksonville, Florida, United States, 32224
        • Mayo Clinic
    • Tennessee
      • Nashville, Tennessee, United States, 37203
        • TriStar Bone Marrow Transplant
    • Texas
      • Houston, Texas, United States, 77030
        • MD Anderson Cancer Center
      • San Antonio, Texas, United States, 78229
        • Methodist Healthcare

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: SENTI-202 CAR NK cell therapy

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

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.

Other Names:
  • Fludarabine
  • Cytarabine (ara-C)

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Safety and tolerability for dose determination of SENTI-202
Time Frame: 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
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
Time Frame: 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
Through study completion, up to 2 years

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Pharmacokinetic (PK) and pharmacodynamic (PDn) profile of SENTI-202
Time Frame: 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
Through study completion, up to 2 years
Host immune response to SENTI-202
Time Frame: Through study completion, up to 2 years
Anti-SENTI-202 immune response and RCR will be measured in blood samples
Through study completion, up to 2 years
For subjects enrolled in the Dose Finding Cohorts: Anti-cancer activity of SENTI-202
Time Frame: 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
Through study completion, up to 2 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Senti Biosciences

Investigators

  • Study Director: Rochelle Emery, MD, Senti Biosciences, Medical Director

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

April 22, 2024

Primary Completion (Estimated)

February 1, 2026

Study Completion (Estimated)

August 1, 2040

Study Registration Dates

First Submitted

March 13, 2024

First Submitted That Met QC Criteria

March 19, 2024

First Posted (Actual)

March 22, 2024

Study Record Updates

Last Update Posted (Actual)

February 12, 2026

Last Update Submitted That Met QC Criteria

February 10, 2026

Last Verified

February 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • SENTI-202-101

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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