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

Senti Biosciences

Status and phase: Enrolling; Phase 1

Conditions: AML/MDS; CD33 Expressing Hematological Malignancies; FLT3 Expressing Hematological Malignancies

Treatments: Biological: SENTI-202

Study type: Interventional

Funder types: Industry

Identifiers

NCT06325748

SENTI-202-101

Details and patient eligibility

About

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.

Full 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).

Enrollment: 21 estimated patients

Sex: All

Ages: 18 to 74 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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21 participants in 1 patient group

SENTI-202 CAR NK cell therapy

Experimental group

Description:

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

Treatment:

Biological: SENTI-202