ACHIEVE2 - Safety and Preliminary Efficacy of Intravenous TCB008 in Patients With Relapse or Refractory Acute Myeloid Leukemia (AML) or Myelodysplastic Syndrome (MDS)/AML — ACHIEVE2  

Acute Myeloid Leukemia Clinical Trial

Official title: An Open-label, Multicenter, Phase 1 Study to Evaluate Safety and Preliminary Efficacy of Intravenous TCB008 in Patients With Relapse or Refractory Acute Myeloid Leukemia (AML) or Myelodysplastic Syndrome (MDS)/AML

Status Not yet recruiting

Clinical Trial Summary

TCB008-003 (ACHIEVE2) is an open-label, multi-center study conducted in 2 parts (dose escalation followed by dose expansion) to evaluate safety, persistence/expansion, and preliminary efficacy of single and multiple intravenous doses of TCB008 in patients with Relapse or Refractory Acute Myeloid Leukemia (AML) or Myelodysplastic Syndrome (MDS)/AML, who have failed or are intolerant to the current standard of care. The dose escalation will follow a 3+3 design with 3 cohorts planned. Once the recommended dose for further investigation has been confirmed, based on dose-limiting toxicities (DLTs), overall safety data, and preliminary efficacy data, up to 20 patients will be enrolled to into one of each of the three dose expansion cohorts.

Clinical Trial Description

TCB008-003 (ACHIEVE2) is an open-label, multi center study conducted in 2 parts (dose escalation followed by dose expansion). The purpose of this study is to evaluate Safety and Preliminary Efficacy of Intravenous TCB008 in Patients with Relapse or Refractory Acute Myeloid Leukemia (AML) or Myelodysplastic Syndrome (MDS)/AML.

TCB008 is derived from the peripheral blood mononuclear cells (PBMCs) of unrelated, healthy donors and consists of expanded cluster designation (CD)3+ T cells expressing the γ-chain variable region 9 δ-chain variable region 2 (Vγ9Vδ2) T cell receptor (TCR); it is infused into patients to boost their immune system. It is currently developed for treatment of cancers and infectious diseases.

Approximately 69 people will take part in this study at several different locations throughout the United States of America.

In both parts of the study, potential patients will be screened to assess their eligibility to enter the study within 35 days prior to the first dose of the investigational medicinal product (IMP). Once enrolled in the study patients will undergo lymphodepletion chemotherapy prior to administration of the IMP using the following regimen: fludarabine (30 mg/m2/day) will be administered from Days -6 to -3 (total 120 mg/m2), cyclophosphamide (0.5 g/m2/day) from Days -5 to -3 (total 1.5 g/m2), followed by 2 days of rest (Days -2 and -1).

The dose escalation part will use a 3+3 design.

The dose escalation part will comprise 3 cohorts of 3 to 6 patients where patients in each cohort will receive up to 4 doses of TCB008 in accordance to the cohort to which they are assigned (initial infusion plus 3 potential reinfusions) with the following dose-level (DL) escalating for each cohort:

Cohort 1: 1.5 mL IV TCB008 (3.6×107 to 6.9×107 cells) Cohort 2: up to 5 mL IV TCB008 (12.0×107 to 23.0×107 cells) Cohort 3: up to 18 mL IV TCB008 (43.2×107to 82.8×107 cells)

Decisions to escalate the dose will be made on any observed DLTs as well as additional supportive data such as overall safety profile from the 28-day DLT evaluation period following the first infusion with TCB008 for all patients of a cohort. The Safety Review Committee (SRC; with agreement from the sponsor [or designee]) may elect to pursue intermediate, lower, or higher DLs based on overall review of safety data. Alternative dosing schedules may also be considered based on the emerging safety data.

The dose expansion part will start once dose escalation has been completed. Once the recommended dose for expansion (RDE) has been confirmed, up to 20 patients will be enrolled into one of each of the following dose expansion cohorts:

Cohort 4: Patients with relapsed or refractory AML or MDS/AML Cohort 5: Patients with previously treated AML or MDS/AML who achieved in their last treatment CR with MRD Cohort 6: Patients with previously treated relapse or refractory adverse risk AML or MDS/AML per ELN guidelines 2022.

For both parts (dose escalation and dose expansion), patients may be reinfused with TCB008 up to 3 times following initial infusion (at the same dose as the initial infusion), if deemed appropriate by the investigator (or designee), based on review of available safety data and confirmation of disease status as defined below:

• CR was not achieved (AML patients) following the first dose of TCB008

• CR was achieved but MRD is present (MRD+ patients) following the first dose of TCB008

• patients' disease did not progress following administration of previous doses of TCB008.

Such reinfusions will not be preceded by lymphodepletion chemotherapy.

For both parts (dose escalation and dose expansion), the study will be conducted as follows:

• screening period: Approximately 4 weeks

• lymphodepletion chemotherapy period (right before Cycle 1): Approximately 1 week

• treatment period: Up to 16 weeks from the first dose of IMP (TCB008)

• follow-up period: Approximately 24 months from the last dose of IMP (TCB008).

Patients will be monitored for safety, tolerability, persistence/expansion, and preliminary efficacy throughout the study. Tumor response will be assessed according to ELN 2022 guidelines, 28days after the initial infusion, and second, third, and fourth reinfusions (as applicable), and starting at 6 months (±7 days), approximately every 3 months (±7 days) during the follow-up period. Optional disease assessment may be performed at the investigator (or designee)'s discretion, 14 days after the initial infusion, and second, third, and fourth reinfusions (as applicable).

Patients who discontinue treatment due to other reasons than disease progression will continue with cancer assessments as per protocol until disease progression, patient refusal, death, or starting a new anticancer treatment. The total duration of study participation for each patient (from screening through end of study visit) is anticipated to be approximately 29 months. ;

Related Conditions & MeSH terms

• Acute Myeloid Leukemia
• Leukemia
• Leukemia, Myeloid
• Leukemia, Myeloid, Acute
• Myelodysplastic Syndromes
• Preleukemia
• Syndrome

• NCT number: NCT06463327
• Study type: Interventional
• Source: TC Biopharm
• Status: Not yet recruiting
• Phase: Phase 1
• Start date: January 2025
• Completion date: June 2027