The Food & Drug Administration (FDA) has issued a ‘safe to proceed’ for the Investigational New Drug (IND) application for PRAME TCR/IL-15 NK (SY-307), an engineered T cell receptor natural killer (TCR NK) cell therapy for relapsed/refractory myeloid malignancies. 

The engineered PRAME-targeted TCR NK cell therapy is developed from cord blood-derived NK cells that express a high affinity TCR targeting the PRAME tumour-associated neoantigen.

PRAME is highly immunogenic and expressed on numerous different cancer types, including haematologic malignancies such as acute myeloid leukaemia (AML) and myelodysplastic syndromes (MDS), and solid tumours such as melanoma, sarcoma, and ovarian, endometrial, lung and breast cancer.

The ability of PRAME to elicit humoral and cellular immune responses, along with its restricted tissue expression, establishes it as a compelling target for cell therapy-mediated cancer immunotherapy.

The Phase I/II open-label study will assess the safety, tolerability and preliminary efficacy of PRAME TCR/IL-15 NK (SY-307) in patients with relapsed/refractory AML and MDS.

It will be administered following lymphodepletion with standard doses of fludarabine/cyclophosphamide (Flu/Cy) and decitabine. Up to 44 patients will be enroled into the study, which is anticipated to commence in Q3 2024.

“PRAME is expressed at high levels in multiple different tumour types, making it a compelling target for engineered TCR NK cancer immunotherapy. The recent IND clearance of our PRAME TCR/IL-15 NK (SY-307) program for AML and MDS represents a significant expansion of Syena’s growing pipeline of “off-the-shelf" engineered TCR NK therapies and complements our existing NY-ESO-1 targeted programs in myeloma and sarcoma,” said Adrian Woolfson, executive chairman, president and co-founder of Replay.

“PRAME is a well-known cancer-testis antigen with re-expression in multiple cancer types, including AML and solid tumours, and restricted expression on normal tissues,” said Arun Balakumaran, M.D., Ph.D., chief medical officer at Replay. “This dichotomous expression pattern and its ability to elicit spontaneous humoral and cellular immune responses render it a promising target for cancer immunotherapy.”

“This is an exciting milestone in the development of 'off-the-shelf' engineered TCR NK cell therapies to address significant unmet medical needs,” Rezvani said. “Our hope is the PRAME studies, initially in haematological malignancies and then in solid tumours, will further advance our understanding of the potential for engineered TCR-modified NK cells to benefit patients with relapsed/refractory myeloid malignancies.”

Source: MD Anderson Cancer Center