A phase I study to investigate the safety of TEG001 cell suspension for infusion in patients with relapsed/refractory Acute Myeloid Leukemia/high-risk Myelodysplastic Syndrome (IPSS-R score >4,5) relapsed/refractory or Multiple Myeloma

In order to further the success of immunotherapies, it is key to improve on the
efficacy and applicability of a therapy and simultaneously diminish the
occurrence of severe side effects. TEG001 cell suspension for infusion (TEG001
product) consists of autologous αβT cells, genetically transduced to express a
specific γδT cell receptor derived from a healthy donor. The γδTCR is able to
recognise various types of malignant cells. TEG therapy aims to provide a
lifelong protection against malignancies, without affecting healthy tissue. In
the future, it is the aim for TEG therapy to serve as a curative treatment in
various haematological and solid malignancies.

This study has been transitioned to CTIS with ID 2024-517381-42-00 check the CTIS register for the current data.

This study aims to assess the safety of TEG001. Furthermore, the feasibility of
TEG001 production with material from intensively pre-treated patients and
TEG001 efficacy parameters will be assessed.

This study follows a 3+3 dose escalation design

Cohort 1: 3 Patients receive de first study dose TEG001.
(A) 0 Patients with DLT(s) -> escalate to cohort 2.
(B) 1 Patient with DLT(s) -> include another 3 patients into cohort 1, only 0
DLT(s) in these additional patients will allow to escalate to the next cohort
(C) >1 Patient with DLT(s) -> DSMB.

Cohort 2: 3 Patients receive de second study dose TEG001.
(A) 0 Patients with DLT(s) -> escalate to cohort 3.
(B) 1 Patient with DLT(s) -> include another 3 patients into cohort 2, only 0
DLT(s) in these additional patients will allow to escalate to the next cohort.
(C) >1 Patient with DLT(s) -> MTD is the dose level of the previous cohort,
DSMB.

Cohort 3: 3 Patients receive de third study dose TEG001.
(A) 0 Patients with DLT(s) -> MTD has not been reached.
(B) 1 Patient with DLT(s) -> include another 3 patients into cohort 2, only 0
DLT(s) in these additional patients means the MTD has not been reached.
(C) >1 Patient with DLT(s) -> MTD is the dose level of the previous cohort,
DSMB.

The intervention consists of a single infusion of TEG001 product.

Depending on the underlying haematological malignancy, various tests will be
performed in order to determine the disease status. Furthermore, cardiac,
pulmonary and brain function will be assessed in order to assess if a patient
is physically strong enough to undergo the conditioning chemotherapy, apheresis
and TEG001 product infusion.
Furthermore, subjects will be hospitalised for two weeks to undergo the
preparative chemotherapy, TEG001 product infusion and observation.
After which regular check-ups consisting of physical examination and blood
tests will be performed. Disease status will be re-assessed at day 28 and day
56 after infusion.
To mitigate any risk of this new product in this first in man study, a
population was chosen with only standard of care directed towards support and
symptom relief, but no therapeutic treatment options left. Pre-clinical data
and the mode of action justifies the applicability of TEG001 in a broad patient
population with malignancies. The potential benefit of tumour control in a
patient population with an otherwise dismal outcome, outweighs the burden of
the study procedures and potential side effects.