FDA greenlights IND application of ADI-270 in renal cell carcinoma

The FDA has cleared an investigational new drug (IND) application for ADI-270 to initiate the launch of a phase 1 clinical trial of the therapy in patients with relapsed/refractory renal cell carcinoma (RCC), Adicet Bio announced in a news release.¹

Preliminary clinical data from the trial is expected in the first half of 2025.

ADI-270 is an allogeneic gamma delta chimeric antigen receptor (CAR) T cell therapy candidate targeting CD70-positive cancers.

“ADI-270 is the first ever gamma delta 1 CAR T cell therapy candidate to enter clinical trials for the treatment of solid tumors,” said Chen Schor, president and chief executive officer of Adicet Bio, in the news release.¹ “The FDA’s clearance of our IND application to evaluate ADI-270 in patients with RCC underscores a significant achievement for Adicet. ADI-270 is a third-generation CAR T designed to target CD70+ tumors with high specificity, increased exposure, persistence and tumor infiltration, while addressing immunosuppressive factors in the tumor microenvironment. RCC is the most common type of kidney cancer and has a high unmet need with limited viable treatment options available. With its highly differentiated profile, we believe that ADI-270 has the potential to become an important therapeutic option for patients with RCC and other CD70+ tumors.”

Overall, the multicenter, open-label phase 1 trial plans to evaluate the safety, tolerability, pharmacokinetics, and preliminary anti-tumor activity of ADI-270 in adult patients with relapsed or refractory clear cell RCC. Initial efficacy of the CAR T-cell therapy will be assessed by the overall response rate, duration of response, and disease control rate.

Patients enrolled in the trial will receive a single dose of ADI-270 monotherapy following lymphodepletion, starting at the dose level of 3E8 CAR+ cells. Patients may then be eligible to receive a second dose of ADI-270 if they meet the protocol defined criteria.

According to the company, the phase 1 trial of ADI-270 in clear cell RCC is expected to launch in the second half of 2024, with preliminary clinical data expected in the first half of 2025.

Preclinical data on ADI-270

Preclinical data on ADI-270 were recently presented at the American Society of Gene and Cell Therapy (ASGCT) 27th Annual Meeting in Baltimore, Maryland.² Data showed that ADI-270 significantly inhibited tumor growth in CD70-positive clear cell RCC models, as well as other solid malignancies. The therapy was also shown to exhibit potent in vitro cytotoxicity across a range of cancer cell lines with varying levels of CD70 expression.

Further, the authors wrote, “CAR-mediated killing of CD70(+) tumor cell lines by ADI-270 promoted enhanced γδ T cell activity, including innate and adaptive activity against CD70(-) tumor cells.”

Additional data showed that ADI-270 had robust anti-tumor effects in an in vivo model of clear cell RCC at the earliest time point of assessment (day 3), including tumor infiltration, proliferation, and effector function, which led to the eradication of CD70-positive tumor cells.

Based on these data, the authors determined that further clinical study of the therapy in clear cell RCC and other CD70-positive indications was warranted.

References

1. Adicet Bio announces FDA clearance of IND application for ADI-270 in renal cell carcinoma. News release. Adicet Bio, Inc. Published online and accessed June 24, 2024. https://investor.adicetbio.com/news-releases/news-release-details/adicet-bio-announces-fda-clearance-ind-application-adi-270-renal

2. Chanthery Y, Lamture G, Jahchan N, et al. ADI-270: An Armored Allogeneic Anti- CD70 CAR γδ T Cell Therapy Designed for Multiple Solid and Hematological Cancer Indications. American Society of Gene and Cell Therapy (ASGCT) 27th Annual Meeting. May 7-11, 2024. Baltimore, Maryland. Abstract 329. https://www.adicetbio.com/file.cfm/42/docs/asgct_2024_abstract_final.pdf