ADI-270 Gains FDA Fast Track Status in Metastatic/Advanced ccRCC

• A fast track designation has been given to ADI-270 from the FDA for treating metastatic or advanced clear cell renal cell carcinoma (ccRCC) previously treated with an immune checkpoint inhibitor and a VEGF inhibitor.
• ADI-270 is an allogeneic, off-the-shelf, CD70-targeted gamma delta chimeric antigen receptor (CAR) T-cell therapy candidate.
• A phase 1/2 trial (NCT06480565) plans to assess ADI-270 in patients with histologically or cytologically confirmed ccRCC who have documented evidence of advanced or metastatic disease.

The FDA has granted fast track designation to ADI-270 for the treatment of patients with metastatic or advanced ccRCC who received prior treatment with an immune checkpoint inhibitor and a VEGF inhibitor.¹

“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,” said Chen Schor, president and chief executive officer of Adicet Bio, in a press release. “ccRCC 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.”

ADI-270 is an investigational treatment that utilizes readily available, off-the-shelf gamma delta T cells engineered to target the CD70 protein on cancer cells. By leveraging the natural CD27 receptor for recognition and incorporating a mechanism to resist the suppressive tumor environment, ADI-270 potentially offers advantages in specificity and efficacy.

Additionally, ADI-270 incorporates a mechanism to resist the immunosuppressive tumor environment and minimize the risk of graft-vs-host disease, a concern with allogeneic therapies.

Early research on ADI-270 is encouraging, specifically with preclinical studies presented at the 2023 American Society of Gene and Cell Therapy Meeting, showing that the treatment expanded effectively without harming healthy T cells. A less differentiated T-cell memory phenotype with low expression of exhaustion markers, potent in vitro cytotoxicity, and favorable cytokine and chemokine profiles each were observed with ADI-270.²

Studies via xenografts in immunodeficient mice also showed potent tumor cell killing. Notably, the engineered T cells infiltrated the tumors, multiplied, and became activated within the tumor microenvironment, suggesting they could target the cancer directly.

Kidneys, adrenal glands, genitourinary system, body scan, joint, medical screen 3D render, human anatomy, computer anatomy, body skeleton, X-ray scan: © Leo Viktorov - stock.adobe.com

About the Phase 1/2 Trial of ADI-270

Now, a phase 1/2 trial plans to evaluate ADI-270 in patients aged 18 years and older with histologically or cytologically confirmed ccRCC who have documented evidence of advanced or metastatic disease.³ Once enrolled, patients will undergo lymphodepletion with fludarabine and cyclophosphamide before being treated with a single dose of ADI-270.

Patients are required to have received previous therapy with an immune checkpoint inhibitor and a VEGF inhibitor that has been given in the advanced/metastatic setting, have at least 1 measurable target lesion per RECIST v1.1 criteria, and have a Karnofsky performance status of at least 70. The trial also requires patients to be at least 3 weeks or 5 half-lives removed from their last dose of prior therapy.

In the dose-escalation portion of the study, investigators will give ADI-270 to patients at ascending dose levels which will be used to determine the maximum tolerated dose (MTD) or maximum assessed dose (MAD). The dose-expansion portion will then continue to evaluate the CAR T-cell therapy at the MTD or MAD.

The incidence of dose-limiting toxicities and the proportion of treatment-emergent and -related adverse effects serve as the primary end points of the trial.

REFERENCES:

1. Adicet Bio receives FDA fast track designation for ADI-270 in metastatic/advanced clear cell renal cell carcinoma. News release. Adicet Bio. July 8, 2024. Accessed July 8, 2024. https://tinyurl.com/aubaxy4v

2. Lamture G, Teague AG, Smith-Boeck M, et al. ADI-270: an armored allogeneic “off-the-shelf” CAR γδ T cell therapy targeting CD70+ cancers. Presented at: 2023 American Society of Gene + Cell Therapy; May 16-20, 2023; Los Angeles, CA.

3. A phase 1/​2 trial of ADI-270 in ccRCC. ClinicalTrials.gov. Updated Jun 28, 2024. Accessed July 8, 2024. https://clinicaltrials.gov/study/NCT06480565