A phase 1/2 first in human study of ADI-270, an armored allogeneic antiCD70 chimeric antigen receptor (CAR).dT cell therapy, in patients (pts) with relapsed or refractory (R/R) clear cell renal cell carcinoma (ccRCC) (trial in progress) Free

BACKGROUND: CD70 is a type II transmembrane protein of the tumor necrosis factor superfamily normally transiently expressed in activated lymphocytes, including B, T, NK, and mature dendritic cells. CD70 is aberrantly expressed in solid and hematologic cancers and is implicated in enhanced growth, metastasis, and immune evasion and suppression. In ccRCC, CD70 expression is increased in the tumor microenvironment and on malignant cells. Despite advancements in the treatment of patients with metastatic RCC, the 5 year survival rate is 15% and there remains an unmet need. ADI-270 is an investigational, allogeneic, CD70 targeting (CD27 receptor based) Vδ1 γδ CAR T cell product expressing a dominant negative form of the TGFβ receptor II (dnTGFβRII) to provide resistance against an immunosuppressive tumor microenvironment. γδ T cells possess innate and adaptive immune response functions and a natural role in immune surveillance and anti tumor immunity, including the ability to home to tissues and recognize tumors through multiple antigens. γδ T cells are ideal for an allogeneic cell therapy as their TCR recognizes MHC independent antigens and avoids the risk of graft versus host disease without the need for gene editing. ADI-270 has demonstrated potent preclinical activity against CD70 expressing hematological and solid tumors expressing a range of CD70 levels both in vitro and in mouse xenograft models. Furthermore, ADI-270 demonstrated superior activity against tumors expressing low levels of CD70 when compared to scFv based αβ CAR T cell benchmarks currently in clinical development. METHODS: ADI-202427001 (NCT06480565) is a phase 1 / 2 open label, dose escalation and dose expansion study evaluating ADI-270 in adult pts with R/R ccRCC. Inclusion criteria include confirmed diagnosis of R/R advanced/metastatic ccRCC, previous treatment with an immune checkpoint and VEGF inhibitor; exclusion criteria include previous CD70 targeting treatment and autoimmune disease requiring systemic immunosuppressive therapy. Objectives of phase 1 include characterizing the safety and tolerability of ADI-270, identifying the RP2D for phase 2, and assessing cellular kinetics, immunogenicity, pharmacodynamics (PD), and efficacy; objectives of phase 2 include characterizing the efficacy, safety, immunogenicity, and PD profile of ADI-270 at the RP2D. Safety, efficacy, CK, and PD data from Phase 1 will determine the RP2D for Phase 2. Response will be evaluated per RECIST 1.1 criteria. Additional efficacy analyses include duration of response, progression free survival, and overall survival. Enrollment in study ADI-202427001 is ongoing.