Adicet Bio Gets FDA Nod for ADI-270 IND in Renal Cell Carcinoma

Adicet Bio, Inc., a clinical-stage biotechnology company specializing in developing allogeneic gamma delta T cell therapies for autoimmune diseases and cancer, has announced a significant milestone. The U.S. Food and Drug Administration (FDA) has approved their Investigational New Drug (IND) application for ADI-270. This groundbreaking therapy is an allogeneic "off-the-shelf" gamma delta chimeric antigen receptor (CAR) T cell therapy candidate targeting CD70-positive cancers. The focus will be on treating relapsed or refractory renal cell carcinoma (RCC).

ADI-270 is unique as it is the first gamma delta 1 CAR T cell therapy to enter clinical development for solid tumors. According to Chen Schor, President and CEO of Adicet Bio, the FDA’s clearance marks a significant accomplishment for the company. ADI-270 is engineered to target CD70+ tumors with high specificity, increased persistence, and effective tumor infiltration. It also addresses immunosuppressive factors within the tumor microenvironment. With RCC being the most common type of kidney cancer and having limited treatment options, ADI-270 is poised to potentially become a crucial therapeutic option for RCC and other CD70+ tumors.

The Phase 1 clinical trial, set to begin in the second half of 2024, aims to assess the safety and anti-tumor activity of ADI-270 in RCC patients. This multicenter, open-label study will involve adults with relapsed or refractory clear cell RCC. Patients will undergo lymphodepletion before receiving a single dose of ADI-270. The starting dose level will be 3E8 CAR+ cells, with the possibility of a second dose depending on meeting the protocol-defined criteria.

The trial will include dose escalation and dose expansion phases, evaluating safety, tolerability, pharmacokinetics, and anti-tumor activity. Key metrics will include the overall response rate, duration of response, and disease control rate.

ADI-270 stands out due to its sophisticated design. It employs a third-generation CAR to target CD70 through its natural receptor, CD27, as the binding moiety. Additionally, it is armored with a dominant negative form of the Transforming Growth Factor-β receptor II (dnTGFβRII) to counteract the immunosuppressive tumor microenvironment. This engineering aims to boost exposure and persistence by minimizing susceptibility to host versus graft elimination. These attributes, combined with the potent tumor infiltration capabilities of gamma delta 1 T cells, are expected to enhance clinical responses in RCC patients and others with CD70+ tumors.

Renal cell carcinoma (RCC) is the most prevalent type of kidney tumor, making up 80% to 85% of primary renal neoplasms. The most common subtype, clear cell RCC (ccRCC), accounts for 80% of all RCC cases. Known for its aggressiveness, ccRCC often originates from renal stem cells found in the proximal nephron and tubular epithelium and frequently metastasizes to the lungs, liver, and bones. Approximately 20% of new RCC cases are either locally advanced or metastatic, and up to 30% of patients may develop metastatic disease post-nephrectomy. While the 5-year survival rate for localized RCC is 93%, it significantly drops to 15% for advanced disease.

Adicet Bio, Inc. continues to push the boundaries in biotechnology by advancing its pipeline of "off-the-shelf" gamma delta T cells engineered with CARs to provide lasting activity in patients. ADI-270 stands as a promising candidate that could potentially revolutionize the treatment landscape for RCC and other CD70+ tumors. The company looks forward to commencing its Phase 1 trial and anticipates preliminary clinical data by the first half of 2025.