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.
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
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
21
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.
UCLA Medical Center
Los Angeles, California, United States
Colorado Blood Cancer Institute
Denver, Colorado, United States
Mayo Clinic
Jacksonville, Florida, United States
TriStar Bone Marrow Transplant
Nashville, Tennessee, United States
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 and dosing regimen
Time frame: 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
The response rate to SENTI-202 will be measured using clinical measures of benefit as defined by standard consensus criteria for the respective disease
Time frame: Through study completion, up to 2 years
For subjects enrolled in the Dose Finding Cohorts: 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
Time frame: 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
Time frame: 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
Time frame: Through study completion, up to 2 years
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MD Anderson Cancer Center
Houston, Texas, United States
Methodist Healthcare
San Antonio, Texas, United States
Royal Prince Alfred Hospital
Camperdown, New South Wales, Australia
Peter MacCallum Cancer Center
Melbourne, Victoria, Australia