(UroToday.com) The 2025 American Society of Clinical Oncology (ASCO) Annual Meeting held in Chicago, IL between May 30 and June 3 was host to the Poster Session: Genitourinary Cancer - Kidney and Bladder. Dr. Sumanta Kumar Pal, presented the trial in progress Poster TPS4613: A phase 1/2 first in human study of ADI-270, an armored allogeneic anti-CD70 chimeric antigen receptor γδ T cell therapy, in relapsed or refractory (R/R) clear cell renal cell carcinoma (ccRCC).
Dr. Pal began by highlighting CD70 as a type II transmembrane protein in the tumor necrosis factor (TNF) superfamily, typically expressed transiently in activated lymphocytes, including B cells, T cells, NK cells, and mature dendritic cells. In contrast, aberrant and sustained CD70 expression is observed across a range of solid and hematologic malignancies, where it contributes to tumor growth, metastasis, immune evasion, and suppression. In clear cell renal cell carcinoma (ccRCC), CD70 expression is notably elevated both in malignant cells and within the tumor microenvironment. Despite advances in metastatic RCC therapy, the 5-year survival rate remains approximately 15%, underscoring the urgent need for novel treatment strategies.
ADI-270 is an investigational, allogeneic Vδ1 γδ chimeric antigen receptor (CAR) T cell therapy that targets CD70 via a CD27 receptor-based CAR. It incorporates a dominant negative TGFβ receptor II (dnTGFβRII) to counteract the immunosuppressive effects of TGFβ within the tumor microenvironment. γδ T cells have both innate and adaptive immune functions, tissue-homing capabilities, and recognize antigens independently of MHC, making them well-suited for allogeneic use with minimal risk of graft-versus-host disease.
Preclinical studies show that ADI-270 has potent anti-tumor activity against CD70-expressing hematologic and solid tumors, including ccRCC, across a range of CD70 expression levels. Notably, ADI-270 outperformed scFv-based αβ CAR T cell comparators in models of low CD70-expressing tumors, supporting its potential clinical utility in targeting this difficult-to-treat patient population.1
ADI-202427001 (NCT06480565) is a multicenter, phase 1/2 open-label, dose-escalation and dose-expansion study evaluating ADI-270 in adult patients with relapsed or refractory ccRCC. Key inclusion and exclusion criteria are summarized below.
Key Inclusion Criteria:- Histologically confirmed advanced or metastatic relapsed/refractory (R/R) clear cell renal cell carcinoma (ccRCC)
- Prior treatment with both an immune checkpoint inhibitor and a VEGF inhibitor
- Karnofsky performance status ≥ 70
- Prior treatment with a CD70-targeting agent
- Autoimmune disease requiring systemic immunosuppressive therapy
The ADI-202427001 study will be divide into two phase. The objectives of each phase are summarized below:
Phase 1 Objectives:- Characterize the safety and tolerability of ADI-270
- Determine the recommended phase 2 dose (RP2D)
- Assess cellular kinetics (CK)
- Evaluate immunogenicity and pharmacodynamics (PD)
- Assess preliminary anti-tumor activity
- Evaluate anti-tumor activity of ADI-270 at the RP2D
- Further characterize safety, immunogenicity, CK, and PD profile
- Response assessment using RECIST v1.1 criteria
- Additional efficacy endpoints: duration of response, progression-free survival (PFS), and overall survival (OS)
Enrollment for ADI-202427001 is currently ongoing.
Presented by: Sumanta Kumar Pal, MD, FASCO, Department of Medical Oncology, City of Hope Comprehensive Cancer Center, Los Angeles, CA.
Written by: Julian Chavarriaga, MD – Urologic Oncologist at Cancer Treatment and Research Center (CTIC) via Society of Urologic Oncology (SUO) Fellow at The University of Toronto. @chavarriagaj on Twitter during the American Society of Clinical Oncology (ASCO) 2025 Annual Meeting, Chicago, IL, Fri, May 30 – Tues, Jun 3, 2025.
Reference:
- Beckermann K, Rini B, Aftab BT, et al,. 640 A phase 1/2 first in human study of ADI-270, an armored allogeneic anti-CD70 chimeric antigen receptor γδ T cell therapy, in patients with relapsed or refractory clear cell renal cell carcinoma Journal for ImmunoTherapy of Cancer 2024;12:doi: 10.1136/jitc-2024-SITC2024.0640