Phase 1/2 trial launches of CAR T cell therapy for ccRCC

A phase 1/2 trial (NCT06480565) of ADI-270 is now enrolling patients with relapsed or refractory clear cell renal cell carcinoma (ccRCC), according to a news release from Adicet Bio, the developer of the therapy.¹

In total, the trial expects to enroll 60 patients.

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.

Initial results from the phase 1 portion of the trial are anticipated for the first half of 2025.

“Solid tumors represent one of the highest unmet medical needs in oncology and have yet to benefit from the breakthroughs observed with CAR T cell therapies in hematologic malignancies. Emerging data from ADI-270, our armored allogeneic 'off the shelf' gamma delta 1 CAR T cell therapy targeting CD70 positive cancers, have shown potential in addressing this gap,” said Chen Schor, president and CEO of Adicet, in the news release.¹ “At the recent ASGCT conference, we presented preclinical data in which ADI-270 demonstrated significant tumor infiltration, resistance to the immunosuppressive tumor microenvironment, and potent activity via CAR and innate-mediated targeting, highlighting its potential for treating solid tumors. We look forward to enrolling patients and anticipate sharing preliminary clinical data from the trial in the first half of 2025.”

Overall, the multicenter, open-label, phase 1/2 dose-escalation/dose-expansion trial will evaluate the safety, tolerability, pharmacokinetics, and preliminary anti-tumor activity of ADI-270 in adult patients with relapsed or refractory ccRCC.² Initial efficacy 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 for the trial are the incidence of dose-limiting toxicities and the proportion of patients with treatment-emergent or treatment-related adverse events.

In total, the trial expects to enroll 60 patients.3 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 opens enrollment for ADI-270 phase 1 clinical trial in metastatic/advanced clear cell renal cell carcinoma. News release. Adicet Bio, Inc. November 18, 2024. Accessed November 19, 2024. https://investor.adicetbio.com/news-releases/news-release-details/adicet-opens-enrollment-adi-270-phase-1-clinical-trial

2. A phase 1/​2 trial of ADI-270 in ccRCC. ClinicalTrials.gov. Last updated June 28, 2024. Accessed November 20, 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 November 19, 2024. https://www.adicetbio.com/file.cfm/42/docs/asgct_2024_abstract_final.pdf