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

PHASE1RECRUITING

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.

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Study details:

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 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).

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Eligibility criteria

Researchers look for people who fit a certain description, called eligibility criteria. See if you qualify.

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.

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Eligibility

Age eligible for study : 18 and older

Healthy volunteers accepted : No

Gender eligible for study: All

Things to know

Study dates

Study start: 2024-04-22

Primary completion: 2025-09-01

Study completion finish: 2040-08-01

Study type

TREATMENT

Phase

PHASE1

Trial ID

NCT06325748

Intervention or treatment

BIOLOGICAL: SENTI-202

Conditions

• AML/MDS
• CD33 Expressing Hematological Malignancies
• FLT3 Expressing Hematological Malignancies

Condition: AML/MDS, CD33 Expressing Hematological Malignancies and more
BIOLOGICAL: SENTI-202
Camperdown, New South Wales, Australia and more
Sponsor: Senti Biosciences

You may be eligible to participate in this trial based on your search. Check eligibility by answering some questions.

Are you running this trial? If you're a clinic or sponsor, you can claim this study. Claim or learn more.

Find a site

Closest Location:

Royal Prince Alfred Hospital

Research sites nearby

Select from list below to view details:

Royal Prince Alfred Hospital
Camperdown, New South Wales, Australia
Peter MacCallum Cancer Center
Melbourne, Victoria, Australia

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?

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 3 weekly doses (Days 0, 7, 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.

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 3 weekly doses (Days 0, 7, 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.

What is the study measuring?

Primary outcome

Primary Outcome Measure	Primary Outcome Description	Primary Outcome Time Frame
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	At the end of each treatment cycle (each cycle is 28 days) and through study completion, up to 2 years

Secondary outcome

Secondary Outcome Measure	Secondary Outcome Description	Secondary Outcome Time Frame
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
Pharmacokinetic (PK) and pharmacodynamic (PDn) profile of SENTI-202	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	Anti-SENTI-202 immune response and RCR will be measured in blood samples	Through study completion, up to 2 years

Frequently Asked Questions

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References

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