FDA Grants Fast Track Designation to ADI-270 in Advanced Clear Cell RCC

The FDA cleared an investigational new drug application for ADI-270 in relapsed/refractory RCC in June 2024.

The FDA has granted fast track designation to the investigational CAR T-cell therapy ADI-270 as a treatment for patients with metastatic or advanced clear cell renal cell carcinoma (RCC) previously treated with an immune checkpoint inhibitor and a VEGF inhibitor, according to a press release from the developer, Adicet Bio, Inc.¹

The allogeneic, off-the-shelf agent was designed to target CD70 in cancers by using CD27, its natural receptor, as a binding moiety. The CAR T-cell therapy also makes use of a dominant negative form of the transforming growth factor-β receptor II (dnTGFβRII) to exhibit resilience against the immunosuppressive tumor microenvironment. Investigators hypothesize that treatment with ADI-270 may improve clinical responses in patients with RCC and other CD70-positive disease.

“We are pleased that ADI-270, our first ever gamma delta 1 CAR T-cell therapy candidate to enter clinical trials for solid tumors, has been granted fast track designation by the FDA,” Chen Schor, president and chief executive officer at Adicet Bio, said in the press release.¹ “[Clear cell] RCC is the most common type of kidney cancer, and this significant milestone underscores our commitment to advancing innovative treatments to these patients as quickly as possible.”

According to previous preclinical data presented at the 2024 European Hematology Association (EHA) Congress, ADI-270 demonstrated potent in vitro cytotoxicity within various cancer cell lines expressing differing CD70 levels.² The agent also slowed tumor growth across a range of xenograft models, including those for CD70-positive T-cell lymphoma, clear cell RCC, and non–small cell lung cancer. Among the clear cell RCC models, investigators reported robust tumor infiltration, proliferation, and effector function at 3 days after administering ADI-270, consequently yielding CD70-positive tumor cell eradication.

“These results demonstrate the activity of ADI-270 in multiple solid and hematological cancers, which includes innate anti-tumor immunity, potent next-generation CAR targeting, and resilience to attenuation by TGFβ,” the study authors wrote.² “Based on the functional characterization demonstrated to date, further clinical evaluation of ADI-270 is warranted in [clear cell] RCC and additional CD70-positive solid and hematological malignancies.”

Investigators will evaluate treatment with ADI-270 for patients with relapsed or refractory clear cell RCC as part of a phase 1/2 trial (NCT06480565).³ In this multicenter, open-label, dose-escalation, and dose-expansion study, patients will receive ADI-270 in combination with lymphodepleting chemotherapy consisting of fludarabine and cyclophosphamide.

The study’s primary end point is the maximum tolerated dose or maximum assisted dose. The incidence of treatment-emergent adverse effects (TEAEs) and treatment-related AEs is another primary end point.

Patients 18 years and older with histologically or cytologically confirmed clear cell RCC and evidence of advanced or metastatic disease are eligible for enrollment on the trial. Other requirements for study entry include having prior treatment with an immune checkpoint inhibitor and a VEGF inhibitor, at least 1 measurable lesion per RECIST v1.1 guidelines, and a Karnofsky performance status of at least 70.

Those with central nervous system metastases, spinal cord compression, or prior radiotherapy within 3 weeks of beginning study treatment are not eligible for enrollment. Patients are also ineligible for study entry if they have prior treatment with gene therapy within 6 weeks of receiving lymphodepleting chemotherapy, prior anti-CD70 therapy, any primary immunodeficiency, or active autoimmune disease requiring management with ongoing systemic immunosuppressive therapy.

The FDA cleared an investigational new drug application for ADI-270 in relapsed/refractory RCC in June 2024.⁴ According to a press release, investigators anticipate initiating their phase 1 assessment of ADI-270 in the second half of 2024 and plan to share preliminary findings in the first half of 2025.

References

1. Adicet Bio receives FDA fast track designation for ADI-270 in metastatic/advanced clear cell renal cell carcinoma. News release. July 8, 2024. Accessed July 9, 2024. https://tinyurl.com/ueyn5avp
2. Chanthery Y, Lamture G, Jahchan N, et al. ADI-270: an armored allogeneic anti-CD70 CAR gamma-delta T cell therapy designed for multiple solid and hematological cancer indications. Presented at the Presented at: 2024 European Hematology Association Congress; June 13-16, 2024; Madrid, Spain. Abstract P1433.
3. A phase 1/​2 trial of ADI-270 in ccRCC. ClinicalTrials.gov. Accessed July 9, 2024. https://tinyurl.com/ynm4t7p6
4. Adicet Bio announces FDA clearance of IND application for ADI-270 in renal cell carcinoma. News release. Adicet Bio. June 24, 2024. Accessed July 9, 2024. https://tinyurl.com/4f627s77