Off-the-shelf CAR-T produces complete remission in patient with advanced kidney cancer

Treatment with CTX130, a novel chimeric antigen receptor T-cell therapy, led to disease control in more than three quarters of patients with advanced clear cell renal cell carcinoma, results from a phase 1 trial showed.

Data from the COBALT-RCC study presented at Society for Immunotherapy of Cancer Annual Meeting also revealed one patient with stage IV disease experienced complete remission lasting more than 2 years after a single infusion of the investigational agent, researchers noted.

CTX130 (CRISPR Therapeutics) is an allogeneic, CRISPR/Cas9 gene-edited CAR T-cell therapy that targets CD70, an antigen known to be expressed by certain solid tumors and hematologic malignancies.

Kidney cancer is one of the most common cancer types, with about 50,000 patients diagnosed in the U.S. annually, according to Sumanta K. Pal, MD, co-director of City of Hope's kidney cancer program and a HemOnc Today Editorial Board Member.

Clear cell is the most common subtype among patients with renal cell carcinoma — comprising approximately 70% to 80% of cases — and tends to respond poorly to currently available therapies, he added.

 

“Ultimately, up to 30% of patients will develop metastases, and this will require systemic therapy,” Pal said during a presentation. “Our study is predicated on the fact that renal cell carcinoma, especially clear cell disease, appears to have relatively high and consistent expression of CD70.”

 

 

The multicenter phase 1 COBALT-RCC trial enrolled 14 adults (median age, 64.5 years; range, 54-77) with stage IV relapsed or refractory unresectable or metastatic clear cell renal cell carcinoma to evaluate the safety and efficacy of CTX130. The study included heavily pretreated patients with previous exposure to both immune checkpoint and tyrosine kinase inhibitors.

Patients received standard lymphodepleting chemotherapy followed by a single infusion of CTX130 at one of four dose levels, ranging from 3 × 107 to 9 × 108 CAR T cells.

Safety and dose-limiting toxicity served as the primary endpoints for the dose-escalation portion of the study, with a data cutoff point of May 2, 2022. Objective response rate served as the primary endpoint for the dose-expansion portion of the study.

A single infusion of CTX130 conferred a disease control rate of 76.9% among the 14 patients who received the investigational therapy.

Investigators reported stable disease in nine patients (69.2%)

that lasted at least 4 months in four patients (30.8%).

One patient (7.7%) experienced a durable complete remission that is ongoing as of their 24-month follow-up, Pal confirmed during the presentation.

Researchers found that CAR T-cell expansion occurred across all four dose levels evaluated, with a developing association between higher dose level and disease control.

Investigators reported no dose-limiting toxicities during the study.

Seven patients (50%) experienced grade 1 or grade 2 cytokine release syndrome, with no cases of grade 3 or higher CRS reported during the study.

Three patients developed serious infections unrelated to treatment with CTX130, including one patient death (grade 5 pneumonia with grade 4 dyspnea).

Further safety analysis showed no occurrence of immune effector cell-associated neurotoxicity syndrome, graft-versus-host disease or hemophagocytic lymphohistiocytosis.

The results of this first-in-human trial of a CD70-targeted CAR T cell therapy in clear cell renal cell carcinoma showed an acceptable safety profile with indicators of efficacy, Pal noted.

"This is encouraging initial antitumor activity and, to our knowledge, represents the first durable complete response to an allogeneic CAR T-cell therapy in a patient with a relapsed or refractory solid tumor,” Pal said.

His group is already working on a second-generation version of the agent that is currently in preclinical testing.

“We are looking to move forward with CTX131, which incorporates additional [gene] edits that we hope will increase the potency of this cell therapy,” he told Healio.

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