Abstract CT111: A phase 1, first-in-human study of IB-T101, an OUTLAST™ CAR-T product for the treatment of CD70-positive clear cell renal carcinoma

Abstract Relapsed/refractory clear cell renal cell carcinoma (ccRCC) presents an unmet medical need for patients as they are faced with limited treatment options and poor clinical outcomes. CD70, is commonly expressed in ccRCC and is an attractive target for chimeric antigen receptor T cell (CAR-T) therapy. IB-T101 is an autologous CAR-T targeting CD70 that has been expanded under OUTLAST™ conditioning. OUTLAST™ conditioning is easy to implement during cell expansion and results in CAR-T cells that exhibit an early memory T cell phenotype, are resistant to suppressive signals from the tumor microenvironment, and exhibit increased persistence. These attributes are expected to lead to superior clinical outcomes for IB-T101 CAR-T cells in an ccRCC solid tumor setting. Here we present an in-progress phase 1, first-in-human, open label, multi center investigator-initiated clinical trial aimed at evaluating the safety and efficacy of IB-T101 in ccRCC in patients that have relapsed on prior VEGF targeting therapies alone or in combination with an immune checkpoint inhibitor. Autologous patient T cells are transduced with a lentiviral vector encoding a CD70-targeting CAR and are CRISPR Cas9 gene edited to knock out endogenous CD70, followed by expansion under OUTLAST™ conditioning. Escalating doses of IB-T101 CAR-T cells (150 - 500 x 106) will be infused following lymphodepletion. Primary endpoints of the study will assess the safety and tolerability of IB-T101. Additional objectives of the study are to assess the anti-tumor activity and the pharmacokinetics of IB-T101. Correlative assessments will include pre-treatment biopsies to assess the level of CD70 expression in the tumor. Citation Format: Bo Liu, Warren Anderson, Mathew Esquivel, Adam Pecoraro, Kate Fagan-Solis, Yuning Lei, Jun Cui, Yarong Liu, Kevin Carbajal, Maximilian Richter, Matthias Schroff. A phase 1, first-in-human study of IB-T101, an OUTLAST™ CAR-T product for the treatment of CD70-positive clear cell renal carcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_2):Abstract nr CT111.