CTX130 Allogeneic CAR T-cell Therapy Shows Tolerability, Intriguing Activity in Advanced RCC


CTX130, an investigational allogeneic, CRISP/Cas9 gene-edited, anti-CD70 CAR T-cell therapy, was found to be safe with early signs of clinical activity in patients with advanced clear cell renal cell carcinoma, according to findings from the phase 1 COBALT-RCC trial.

Sumanta K. Pal, MD

Sumanta K. Pal, MD

CTX130, an investigational allogeneic, CRISP/Cas9 gene-edited, anti-CD70 CAR T-cell therapy, was found to be safe with early signs of clinical activity in patients with advanced clear cell renal cell carcinoma (RCC), according to findings from the phase 1 COBALT-RCC trial (NCT04438083) that were presented during the 2022 SITC Annual Meeting.

Results showed that, of 13 evaluable patients, the objective response rate was 8%, the stable disease (SD) rate was 69%, and the disease control rate was 77%. The 1 response was a partial response that deepened to a complete response (CR) by 3 months with a maintained CR at 18 months. At 4 months, 4 patients were in SD.

The therapy had an acceptable safety profile across all dose levels with no dose-limiting toxicities (DLTs). Of the 14 patients on the study, 50% had grade 1/2 cytokine release syndrome (CRS), 3 of which were related to CTX130. The median time to CRS onset was 1 day with a median duration of 2 days. Three patients had serious adverse events (AEs) that were infections, all of which were unrelated to CTX130. There was 1 death of pneumonia with grade 4 dyspnea, which was not related to treatment.

“This first-in-human clinical trial exploring CD70 CAR T-cell therapy in clear cell renal cell carcinoma showed a tolerable safety profile with no unexpected on-target off-tumor toxicities and encouraging antitumor activity,” lead study author Sumanta K. Pal, MD, a professor in the Department of Medical Oncology and Therapeutics Research, and codirector of the Kidney Cancer Program at City of Hope in Duarte, California, said in a presentation during the meeting. “To our knowledge, this durable complete response is the first to be achieved with allogeneic CAR T-cell therapy in patients with relapsed/refractory solid tumors.”

CD70 is a CD27 ligand that has transient expression on activated lymphocytes and is found to be highly expressed in clear cell RCC tumor samples. CTX130 is a first-in-class, CD70-targeting allogeneic CAR T-cell therapy that is being evaluated in patients with advanced clear cell RCC. The therapy has targeted disruption of the T-cell receptor α constant (TRAC), β2 microglobulin, and CD70 loci. With the use of an adeno-associated virus vector, an anti-CD70 CAR cassette is inserted into the TRAC locus by homology-directed repair.

The CAR T-cell therapy is manufactured from healthy donor T cells that are then selected and edited prior to expansion and cryopreservation for off-the-shelf use. Preclinical data demonstrated encouraging signals in an RCC xenograft model, Pal noted.

In the open-label, multicenter, international, single-arm COBALT-RCC trial, investigators sought to evaluate the safety and efficacy of CTX130 in patients with advanced clear cell RCC. The study had 2 parts: a dose-escalation portion (part A) and a cohort expansion portion (part B).

Patients underwent lymphodepletion with fludarabine at 30 mg/m2 plus 500 mg/m2 of cyclophosphamide for 3 days on days -5, -4, and -3. CTX130 infusion began on day +1 with the dose-escalation design: 3 x 107 (dose level 1), 1 x 108 (dose level 2), 3 x 108 (dose level 3), and 9 x 108 (dose level 4).

To be eligible for enrollment, patients with unresectable or metastatic RCC with clear cell differentiation had to be at least 18 years old and have a body weight of 42 kg or higher. Prior exposure to a checkpoint inhibitor and VEGF inhibitor was required; patients also had to have a Karnofsky performance status of at least 80%, as well as adequate renal, liver, cardiac, and pulmonary organ function.

Those who had prior treatment with anti-CD70 therapy or CAR T cells or any other modified T or natural killer cells were excluded from enrollment, as well as those with a history of central nervous system, cardiac, or pulmonary conditions; and prior solid organ transplantation or bone marrow transplant.

The primary end point of part A of the trial was incidence of adverse events via DLTs; in part B, the primary end point was ORR per RECIST v1.1 criteria. Secondary end points were best overall response, progression-free survival, and overall survival.

The median age was 64.5 years (range, 54-77) and 85.7% of patients were male. All patients had stage IV metastatic disease and previously received systemic therapy; 64.3% and 92.9% of patients received prior radiotherapy and surgery, respectively.

A total 57.1% of patients had International Metastatic Renal Cell Carcinoma Database Consortium intermediate-risk disease while 42.9% of patients had high-risk disease. Estimated glomerular filtration rate <60 mL/min/1.73 m2 were reported in 42.9% of patients. The median time from diagnosis was 4.9 years (range, 0.7-24.0), and the sum of diameters for target lesions was 64 mm (range, 12-141).

The data cutoff date was May 2, 2022.

Pal added that the typical pharmacokinetics were seen with peak time to expansion at a median of day 10 and peak concentration of approximately 3500 copies/µg.


Pal SK, Tran B, Hannen JB, et al. CTX130 allogeneic CRISPR-Cas9–engineered chimeric antigen receptor (CAR) T cells in patients with advanced clear cell renal cell carcinoma: results from the Phase 1 COBALT-RCC study. Presented at: 2022 SITC Annual Meeting; November 8-12, 2022; Boston, MA. Abstract 558.

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