First patient dosed in phase 1 trial of ADI-270 in ccRCC

The first patient has been dosed in the phase 1/2 clinical trial (NCT06480565) of ADI-270 in patients with relapsed or refractory clear cell renal cell carcinoma (ccRCC), Adicet Bio announced in a news release.¹

ADI-270 was granted a fast track designation by the FDA in July 2024.

ADI-270 is an investigational allogeneic gamma delta chimeric antigen receptor (CAR) T cell therapy targeting CD70-positive cancers. The therapy was granted a fast track designation by the FDA in July 2024.

Enrollment for the trial remains ongoing for patients with metastatic/advanced ccRCC, with a target enrollment goal of 60 patients.² Initial data from the trial are expected to be released in the first half of 2025.

“Dosing the first patient in our phase 1 trial of ADI-270 in metastatic/advanced ccRCC is a significant milestone for Adicet as we advance our first gamma delta 1 CAR T cell product candidate for the treatment of solid tumors, one of the highest unmet needs in oncology,” said Chen Schor, president and CEO at Adicet Bio, in the news release.¹ “Patients with ccRCC, the most common type of kidney cancer, have a pressing need for safe and effective treatments, as current therapies offer limited benefits for patients with advanced disease. Based on ADI-270’s encouraging preclinical data generated to date, in which ADI-270 demonstrated significant tumor infiltration, resistance to the immunosuppressive tumor microenvironment, and potent activity via CAR and innate-mediated targeting, we believe ADI-270 has the potential to offer a promising advancement for solid tumors. We anticipate reporting preliminary clinical data from the trial in the first half of 2025.”

Overall, the multicenter, open-label, dose-escalation/dose-expansion trial is evaluating the safety, tolerability, pharmacokinetics, and preliminary anti-tumor activity of ADI-270 in patients with relapsed or refractory ccRCC.² Initial anti-tumor activity of the CAR T-cell therapy will be assessed by the overall response rate, duration of response, and disease control rate.

The primary outcome measures are the incidence of dose-limiting toxicities and the proportion of patients with treatment-emergent or treatment-related adverse events. The dose escalation phase of the study will involve the determination of the maximum tolerated dose (MTD), and the dose expansion phase will confirm the safety/efficacy of the MTD.

Participants are eligible for enrollment in the study if they have histologically or cytologically confirmed ccRCC, documented evidence of advanced or metastatic disease, at least 1 measurable target lesion per RECIST v1.1, and a KPS of 70 or higher. Additionally, patients must have received prior treatment with an immune checkpoint inhibitor and a VEGF inhibitor in the advanced/metastatic setting and be at least 3 weeks, or 5 half-lives, whichever is shorter, from the last dose of prior systemic therapy.

Those 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.

Final completion of the study is anticipated for June 2027.

Preclinical data on ADI-270

Preclinical data on ADI-270 were presented earlier this year at the American Society of Gene and Cell Therapy (ASGCT) 27th Annual Meeting in Baltimore, Maryland.³ 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 ccRCC 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 ccRCC and other CD70-positive indications was warranted.

References

1. Adicet Bio announces first patient dosed in the phase 1 clinical trial of ADI-270 in metastatic/advanced clear cell renal cell carcinoma. News release. Adicet Bio, Inc. Published online and accessed December 19, 2024. https://www.businesswire.com/news/home/20241219243706/en/Adicet-Bio-Announces-First-Patient-Dosed-in-the-Phase-1-Clinical-Trial-of-ADI-270-in-MetastaticAdvanced-Clear-Cell-Renal-Cell-Carcinoma

2. A phase 1/​2 trial of ADI-270 in ccRCC. ClinicalTrials.gov. Last updated June 28, 2024. Accessed December 19, 2024. https://clinicaltrials.gov/study/NCT06480565

3. Chanthery Y, Lamture G, Jahchan N, et al. ADI-270: An armored allogeneic “off-the-shelf” CAR γδ T Cell therapy targeting CD70+ cancers. American Society of Gene and Cell Therapy (ASGCT) 27th Annual Meeting. May 7-11, 2024. Baltimore, Maryland. Abstract 1023. Accessed December 19, 2024. https://www.adicetbio.com/file.cfm/42/docs/asgct_2024_abstract_final.pdf