CELL INTELLIGENCE · 肿瘤细胞治疗研究

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

主要终点：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 · 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 · Through study completion, up to 2 years
次要终点：For subjects enrolled in the Dose Finding Cohorts: Anti-cancer activity of SENTI-202；Pharmacokinetic (PK) and pharmacodynamic (PDn) profile of SENTI-202；Host immune response to SENTI-202

• SENTI-202 CAR NK cell therapy · EXPERIMENTAL · 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

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.