Unique Clinical Pharmacology Considerations for Allogeneic Cell Therapies

Adoptive Cell Therapy (ACT) has evolved as one of the most rapidly expanding branches of cancer immunotherapy due to unprecedented and transformational clinical successes, with regulatory approvals of multiple autologous CD19 and BCMA-targeting Chimeric Antigen Receptor (CAR)-T cell therapies for the treatment of B-cell hematological malignancies. Despite the success, challenges continue to exist for autologous CAR-T therapies including relapse, safety concerns, long ‘vein-to-vein’ time, less flexibility for repeat dosing, high cost and manufacturing hurdles. To address the challenges associated with the autologous CAR-T therapies, ‘off the shelf’ allogeneic cell therapies including CAR-T, CAR-NK, γδ CAR-T, along with others are under investigation. However, the clinical pharmacology learnings and approaches are evolving as clinical data emerge from early stage development programs. These clinical pharmacology approaches for allogeneic cell therapies will play a key role in optimizing dose selection, dosing frequency and regimen, optimizing lymphodepleting regimen, and identifying key patient- and product-specific characteristics impacting clinical outcomes. This symposium presentation will cover the current development landscape of allogeneic cell therapies and then highlight unique clinical pharmacology considerations and learnings from early phase clinical development including: dose-exposure-response relationship, patient- and product-specific factors impacting PK/PD, repeat dosing, and impact of different lymphodepletion regimens. Finally, the presentation will cover unique clinical pharmacology considerations (similarities and differences) for different allogeneic cell therapy platforms (e.g. CAR-T, CAR-NK, γδ CAR-T).