Sponsor decision (No safety concern)

GDX012 is a novel cell therapy developed for the treatment of certain types of cancer, including Acute Myeloid Leukemia (AML). The main aims of the study are to learn how safe GDX012 is, how treatment with GDX012 is tolerated and to determine the best dose of GDX012.

The drug being tested in this study is called GDX012. GDX012 is being tested to evaluate the safety and tolerability in adult participants with AML.

The study will enroll approximately 53 patients in two phases, dose escalation and dose expansion.

During Phase 1 (sequential dose escalation), participants will be assigned to one of the following treatment groups each consisting of 3 to 6 participants to receive GDX012 at one of the three dose levels:

1. GDX012 Dose 1
2. GDX012 Dose 2
3. GDX012 Dose 3

Upon completion of Phase 1, 1 to 2 dose levels will be selected for Phase 2a of the study. At the completion of Phase 2a of the study a single dose may be selected by the sponsor and investigators as the recommended phase 2 dose (RP2D) for future study.

This multi-center trial will be conducted in the United States. The overall time to participate in the study is approximately 14 months.

Inclusion criteria:

1. Total body weight of ≥40 kg.

2. Must have pathologically confirmed relapsed or refractory acute myeloid leukemia (R/R AML) including:

   1. Relapsed AML is defined as ≥5% blasts in the bone marrow (BM) or peripheral blood at any time after achieving a CR, CRh, Cri, or MLFS.
   2. Refractory AML is defined as failure to achieve a CR, CRh, Cri, or MLFS after 1 of the following regimens:

   i. Two courses of intensive induction chemotherapy. ii. At least 2 cycles of hypomethylating agent (HMA) or low-dose, cytarabine-based combination regimen.

   iii. At least 4 cycles of HMA monotherapy.

3. During dose escalation, participants must be ineligible for hematopoietic stem cell transplantation (HSCT).

4. Must have an anticipated life expectancy of >3 months before lymphodepletion.

5. Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1.

6. Participants must have adequate renal, cardiac, hepatic, pulmonary and bone marrow function as defined by the protocol.

Exclusion criteria:

1. Diagnosis of acute promyelocytic leukemia.
2. Has received or plans to receive any of the excluded therapy/treatment within the specified timeframe before lymphodepleting chemotherapy as defined by the protocol.
3. Prior allogeneic HSCT within 3 months of signing informed consent form (ICF) or with ongoing requirement for systemic graft-versus-host therapy.
4. Active central nervous system (CNS) involvement.
5. History of malignancy other than non-melanoma skin cancer or carcinoma in situ (eg. cervix, bladder, breast) low grade prostate cancer without treatment requirement unless in remission without treatment for ≥2 years.

Takeda provides access to the de-identified individual participant data (IPD) for eligible studies to aid qualified researchers in addressing legitimate scientific objectives (Takeda's data sharing commitment is available on https://clinicaltrials.takeda.com/takedas-commitment?commitment=5). These IPDs will be provided in a secure research environment following approval of a data sharing request, and under the terms of a data sharing agreement.

IPD from eligible studies will be shared with qualified researchers according to the criteria and process described on https://vivli.org/ourmember/takeda/. For approved requests, the researchers will be provided access to anonymized data (to respect patient privacy in line with applicable laws and regulations) and with information necessary to address the research objectives under the terms of a data sharing agreement.