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

AML/MDS Clinical Trial

Official 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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06325748
• Other study ID #: SENTI-202-101
• Status: Recruiting
• Phase: Phase 1
• Start date: June 2024
• Est. completion date: August 2040

Study information

• Verified date: May 2024
• Source: Senti Biosciences
• Contact: Amy Alford, MA
• Phone: 650-239-2030
• Email: clinicaltrials[@]sentibio.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 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).

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 21
• Est. completion date: August 2040
• Est. primary completion date: September 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 74 Years

Eligibility

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

Related Conditions & MeSH terms

• AML/MDS
• Hematologic Neoplasms
• Neoplasms

Intervention

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.

Locations

Country	Name	City	State
Australia	Royal Prince Alfred Hospital	Camperdown	New South Wales
Australia	Peter MacCallum Cancer Center	Melbourne	Victoria
United States	Colorado Blood Cancer Institute	Denver	Colorado
United States	MD Anderson Cancer Center	Houston	Texas
United States	Mayo Clinic	Jacksonville	Florida
United States	UCLA Medical Center	Los Angeles	California
United States	TriStar Bone Marrow Transplant	Nashville	Tennessee
United States	Methodist Healthcare	San Antonio	Texas

Sponsors (1)

Lead Sponsor	Collaborator
Senti Biosciences

Countries where clinical trial is conducted

United States,  Australia, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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	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
Secondary	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