Adicet Bio Begins Phase 1 Trial of ADI-270 for Advanced Renal Cancer

Adicet Bio, Inc., a biotech firm specializing in the development of allogeneic gamma delta T cell therapies, has commenced dosing of its first patient in a Phase 1 clinical trial of ADI-270 for individuals with metastatic or advanced clear cell renal cell carcinoma (ccRCC). This type of kidney cancer represents a significant challenge, as current treatment options often fail to provide substantial benefits for patients with advanced stages of the disease.

Chen Schor, the President and CEO of Adicet Bio, emphasized the importance of this milestone in the company's journey to address one of oncology's most pressing unmet needs: effective treatments for solid tumors. The trial's initiation marks a significant step in advancing ADI-270, Adicet's first gamma delta 1 CAR T cell product candidate aimed at solid tumors. Encouraging preclinical data has shown ADI-270's potential, highlighting its capabilities in tumor infiltration, resistance to the immunosuppressive tumor microenvironment, and potent activity through CAR and innate-mediated targeting. Adicet Bio anticipates sharing initial clinical data from this trial by mid-2025.

The Phase 1 study is structured as a multicenter, open-label clinical trial focused on evaluating ADI-270 as a standalone therapy in adults with relapsed or refractory metastatic/advanced ccRCC. Participants in the trial undergo lymphodepletion before receiving a single dose of ADI-270, starting with a dose level of 3E8 CAR+ cells. Subject to specific protocol criteria, some patients might qualify for a second dose of ADI-270. The trial includes dose escalation and dose expansion phases to assess the safety, tolerability, pharmacokinetics, and anti-tumor efficacy of ADI-270, with measures such as overall response rate, duration of response, and disease control rate being evaluated.

ADI-270 is a pioneering "off-the-shelf" gamma delta CAR T cell therapy candidate designed to target CD70-positive cancers. CD70 is a strategic target owing to its prevalent expression in both solid tumors and blood-related cancers. ADI-270 employs a third-generation CAR that uses CD27, the natural receptor for CD70, as its binding component. It is further enhanced with a dominant negative form of the transforming growth factor-β receptor II (dnTGFβRII) to withstand the immunosuppressive effects of the tumor environment. Additionally, ADI-270's design aims to improve exposure and persistence by diminishing its vulnerability to host versus graft elimination. Together, these attributes, along with the strong tumor penetration shown by gamma delta 1 T cells, aim to enhance treatment outcomes for patients with RCC and other CD70+ tumors.

Renal cell carcinoma (RCC) is the predominant type of kidney cancer, accounting for 80% to 85% of primary renal tumors. Clear cell RCC (ccRCC), the most common RCC subtype, comprises 80% of all RCC cases. This aggressive form of cancer originates from renal stem cells and often metastasizes to the lungs, liver, and bones. At the time of diagnosis, approximately 20% of RCC cases are locally advanced or metastatic, and up to 30% of patients develop metastatic disease after nephrectomy. The 5-year survival rate for localized RCC is 93%, but it drops to 15% for advanced disease stages.

Adicet Bio, Inc. is focused on discovering and developing allogeneic gamma delta T cell therapies for autoimmune diseases and cancer. The company is driving the development of "off-the-shelf" gamma delta T cells engineered with chimeric antigen receptors (CARs) to provide sustained efficacy in patients.