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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/ct2/show/NCT06325748




Registration number
NCT06325748
Ethics application status
Date submitted
13/03/2024
Date registered
22/03/2024
Date last updated
5/06/2024

Titles & IDs
Public title
SENTI-202: Off-the-shelf Logic Gated CAR NK Cell Therapy in Adults With CD33 and/or FLT3 Blood Cancers Including AML/MDS
Scientific title
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 Hematological Malignancies
Secondary ID [1] 0 0
SENTI-202-101
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
AML/MDS 0 0
CD33 Expressing Hematological Malignancies 0 0
FLT3 Expressing Hematological Malignancies 0 0
Condition category
Condition code
Cancer 0 0 0 0
Leukaemia - Acute leukaemia
Cancer 0 0 0 0
Leukaemia - Chronic leukaemia

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Other interventions - SENTI-202

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


Other interventions: 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.
Intervention code [1] 0 0
Other interventions
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Safety and tolerability for dose determination of SENTI-202
Timepoint [1] 0 0
At the end of each treatment cycle (each cycle is 28 days) and through study completion, up to 2 years
Secondary outcome [1] 0 0
Anti-cancer activity of SENTI-202
Timepoint [1] 0 0
Through study completion, up to 2 years
Secondary outcome [2] 0 0
Pharmacokinetic (PK) and pharmacodynamic (PDn) profile of SENTI-202
Timepoint [2] 0 0
Through study completion, up to 2 years
Secondary outcome [3] 0 0
Host immune response to SENTI-202
Timepoint [3] 0 0
Through study completion, up to 2 years

Eligibility
Key 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
Minimum age
18 Years
Maximum age
74 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key 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 design
Purpose of the study
Treatment
Allocation to intervention
N/A
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
Phase
Phase 1
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
22/04/2024
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
1/08/2040
Actual
Sample size
Target
21
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,VIC
Recruitment hospital [1] 0 0
Royal Prince Alfred Hospital - Camperdown
Recruitment hospital [2] 0 0
Peter MacCallum Cancer Center - Melbourne
Recruitment postcode(s) [1] 0 0
2050 - Camperdown
Recruitment postcode(s) [2] 0 0
3000 - Melbourne
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
California
Country [2] 0 0
United States of America
State/province [2] 0 0
Colorado
Country [3] 0 0
United States of America
State/province [3] 0 0
Florida
Country [4] 0 0
United States of America
State/province [4] 0 0
Tennessee
Country [5] 0 0
United States of America
State/province [5] 0 0
Texas

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Senti Biosciences
Address
Country

Ethics approval
Ethics application status

Summary
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.
Trial website
https://clinicaltrials.gov/ct2/show/NCT06325748
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Rochelle Emery, MD
Address 0 0
Senti Biosciences, Medical Director
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Amy Alford, MA
Address 0 0
Country 0 0
Phone 0 0
650-239-2030
Fax 0 0
Email 0 0
clinicaltrials@sentibio.com
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/ct2/show/NCT06325748