AACR: Novel allogeneic CAR T cell therapy delivers promising early results in patients with metastatic clear cell renal cell carcinoma

Phase I study of CD70-targeting therapy ALLO-316 represents progress in adapting cell therapies for solid tumors

MD Anderson News Release April 17, 2023

ABSTRACT:

The CD70-targeting allogeneic chimeric antigen receptor (CAR) T cell therapy, ALLO-316, demonstrated encouraging response rates and disease control rates in patients with metastatic clear cell renal cell carcinoma (ccRCC), according to results of a Phase I trial led by researchers at Â鶹ӳ»­ MD Anderson Cancer Center and presented today at the .

The ongoing , led by ., assistant professor of Stem Cell Transplantation & Cellular Therapy, is the first-in-human study evaluating ALLO-316 in patients with metastatic ccRCC who failed both checkpoint and tyrosine kinase inhibitors (TKIs).

In 17 patients, the objective response rate (ORR) was 18% and the disease control rate (DCR) was 82%. For nine patients with confirmed CD70+ disease, the ORR was 33% with a DCR of 100%.

¡°As we continue to determine the appropriate dose of ALLO-316 for patients, our results demonstrate not only a manageable safety profile but also very encouraging anti-tumor activity,¡± Srour said. ¡°In this trial, we are using an allogeneic ¡°off-the-shelf¡± CAR T cell product which offers an additional benefit to our patients because we are able to get this novel treatment to our patients much faster.¡±

ALLO-316 is genetically designed to target CD70, which is expressed in a variety of solid tumor cancers and highly expressed in ccRCC, a subtype of kidney cancer. To reduce the risk of graft-versus-host disease (GVHD), the T cell receptor alpha also was disrupted from ALLO-316 cells. Furthermore, the CD52 gene was knocked out to allow the use of ALLO-647, an anti-CD52 monoclonal antibody that depletes host T cells and improves the persistence of allogeneic CAR T cells.

As of November 2022, 18 patients with metastatic ccRCC were enrolled in this multicenter, single arm clinical trial evaluating the safety and preliminary efficacy of ALLO-316. Seventeen patients received an ALLO-316 infusion. The median age of participants was 63, and 82% were male. Patients were required to have prior treatment with immune checkpoint inhibitors and TKIs.

Thus far, patients have received ALLO-316 at escalating does of 40 - 120 X 106 CAR T cells. The study allows doses up to 240 million cells. Patients received an ALLO-316 infusion 48 hours after lymphodepletion conditioning with fludarabine/cyclophosphamide, with or without ALLO-647.

Overall, the treatment had a manageable safety profile. Eleven patients (65%) experienced cytokine release syndrome. No cases of GVHD or immune effector cell-associated neurotoxicity syndrome (ICANS) were observed on the study. The maximum tolerated dose has not yet been reached.

¡°We already know that CAR T cell therapy is effective in patients with hematologic cancers, with several FDA-approved indications. Hence, we are adapting this same strategy for patients with solid tumor cancers,¡± Srour said. ¡°We look forward to our ongoing evaluation of data as we continue to learn about this novel CAR T cell therapy approach in this patient population.¡±

Srour and his colleagues continue to optimize the conditioning and to determine the appropriate dose for the Phase II trial. The trial continues to enroll patients with CD70+ tumors.

The study was funded by Allogene Therapeutics as part of a strategic collaboration with MD Anderson. A complete list of collaborating authors can be found within the abstract .