재발성 또는 불응성 급성 골수성 백혈병 성인의 GDX012 연구

Participants received GDX012 weight-based dose level 1 as an intravenous (IV) infusion on Day 1 of Phase 1, following lymphodepleting chemotherapy. Dose Level 1 was the lowest dose level.

GDX012 suspension for IV infusion.

• TAK-012

Chemotherapy agents (fludarabine/cyclophosphamide) as per standard of care.

Participants received GDX012 weight-based dose level 2 as an IV infusion on Day 1 of Phase 1, following lymphodepleting chemotherapy. Dose Level 2 was higher than Dose Level 1.

GDX012 suspension for IV infusion.

• TAK-012

Chemotherapy agents (fludarabine/cyclophosphamide) as per standard of care.

Participants received GDX012 weight-based dose level 3 as an IV infusion on Day 1 of Phase 1, following lymphodepleting chemotherapy. Dose Level 3 was higher than Dose Level 2.

GDX012 suspension for IV infusion.

• TAK-012

Chemotherapy agents (fludarabine/cyclophosphamide) as per standard of care.

DLTs were defined as events occurring by Day 30 after the first GDX012 infusion considered related to GDX012 if they could not be explained by underlying disease, prior therapy, intercurrent illness, or lymphodepleting chemotherapy. Events were graded according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0. DLTs included severe non-hematologic toxicities (Grade 3-4, unresolved or involving vital organs), Grade ≥3 graft versus host disease (GvHD) graded per the Mount Sinai Acute GvHD International Consortium recommendations and 2014 National Institutes of Health (NIH) Consensus, Grade 3-4 cytokine release syndrome (CRS) or immune effector cell-associated neurotoxicity syndrome (ICANS) per American Society for Transplantation and Cellular Therapy (ASTCT) criteria, Grade ≥3 infusion reactions or tumor lysis syndrome (TLS), persistent cytopenia or marrow hypocellularity, and any Grade 5 toxicity attributable to GDX012.

An adverse event (AE) is any untoward medical occurrence in a participant administered a pharmaceutical product; the untoward medical occurrence does not necessarily have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal (investigational) product whether or not it is related to the medicinal product. This includes any newly occurring event or a previous condition that has increased in severity or frequency since the administration of study drug. TEAEs are defined as any AE that begins on or after the initiation of treatment with a study intervention or any existing event that worsens following exposure to the study intervention.

Percentage of participants with disease response included participants who achieved complete response (CR), complete response with partial hematologic recovery (CRh), or complete response with incomplete hematologic recovery (CRi), based on responses assessed by the investigator according to the 2022 European Leukemia Net [ELN] response criteria for acute myeloid leukemia (AML). CR was defined as the sum of complete remission and complete remission without measurable residual disease (MRD). CRh was defined as the sum of CRh and CRhMRD-. CRi was defined as the sum of CRi and CRiMRD-.

The MRD negative status was defined as (less than) <0.1% detectable disease based on local assessment of bone marrow and/or blood.

DOR was planned to be assessed for participants with CR, CRh, or CRi and was defined as the time from the date of first documented CR, CRh, or CRi to the date of first documented relapse or death from any cause, whichever comes first. CR was defined as the sum of Complete Remission and Complete Remission without MRD. CRh was defined as the sum of CRh and CRhMRD-. CRi was defined as the sum of CRi and CRiMRD- .

EFS was defined as the time from the date of the first GDX012 administration to the date of treatment failure, relapse for those who achieved CR, CRh, or CRi, or death from any cause, whichever came first. CR was defined as the sum of Complete Remission and Complete Remission without MRD (CRMRD-). CRh was defined as the sum of CRh and CRhMRD-. CRi was defined as the sum of CRi and CRiMRD-. EFS was analyzed using the Kaplan-Meier method.

OS was defined as the time from the date of the first GDX012 administration to the date of death from any cause. Participants without documentation of death at the time of analysis were censored at the last contact date. OS was analyzed using the Kaplan-Meier method.