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CAR T cell therapy CTX130 shows safety, efficacy in ccRCC

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“Our trial presents the first and the longest durable response we have seen with an allogeneic, off-the-shelf, CAR T cell therapy in the treatment of refractory solid tumors," says Samer A. Srour, MB ChB, MS.

Data from the phase 1 COBALT-RCC trial (NCT04438083) show durable response and stability with CTX130, a CD70-targeting allogeneic CAR T cell therapy for patients with advanced clear cell renal cell carcinoma (ccRCC).

At the time of data cutoff, disease control was achieved in 81.3% of patients.

At the time of data cutoff, disease control was achieved in 81.3% of patients.

The findings were presented at the 2024 American Association for Cancer Research (AACR) Annual Meeting1 in San Diego, California and concurrently published in Cancer Discovery,2 a journal of the AACR.

“Our trial presents the first and the longest durable response we have seen with an allogeneic, off-the-shelf, CAR T cell therapy in the treatment of refractory solid tumors. These findings are exciting and encouraging as we continue to improve treatment options for patients with clear cell renal cell carcinoma and other high-risk solid tumors who otherwise have poor outcomes,” said lead author Samer A. Srour, MB ChB, MS, in a news release on the findings.3 Srour is an assistant professor of stem cell transplantation & cellular therapy at The University of Texas MD Anderson Cancer Center in Houston.

Patients included the study received CTX130 in 4 dose levels ranging from 3x107 to 9x108 CAR T cells. No dose-limiting toxicities were observed.

Among all patients (n = 16), 8 experienced cytokine release syndrome, with all instances being grade 1 or 2. Further, 4 patients experienced infections that were all deemed to be unrelated to study treatment. No patients experienced hemophagocytic lymphohistiocytosis, graft-vs host disease, or treatment-related neurotoxicity.

At the time of data cutoff, disease control was achieved in 81.3% of patients, including 75% (12) of patients with stable disease (SD) and 1 patient (6.3%) with a complete response of more than 3 years. Of those that achieved SD, 1 patient has extended in excess of 18 months.

The initial median CD70 expression level was 100% based on immunohistochemical staining of baseline and archival tissues. There was no substantial antigenic loss at sequential biopsies performed at day 42. Further, digital droplet PCR assays of the CAR construct showed that expansion generally increased at each dose level.

In total, the first-in-human study treated 16 patients with stage 4 ccRCC across clinical trial sites in the US, Europe, and Australia. The median age of patients was 63 (range, 53-77). At the time of study entry, patients had received a median of 3 prior lines of therapy (range, 1-6).

To be included in the trial, patients needed to have unresectable or metastatic RCC with prior receipt of at least 1 checkpoint inhibitor and tyrosine kinase inhibitor, a body weight of 42 kg or higher, a Karnofsky performance status of 80% or higher, adequate renal, liver, cardiac, and pulmonary organ function, and agreed to use acceptable methods of contraception through at least 12 months from treatment infusion.4

The primary end points for the study are the incidence of adverse events (AEs) and objective response rate per RECIST v1.1. Secondary outcome measures are progression-free survival and overall survival, with assessments up to 60 months.

Following the positive data from the COBALT-RCC trial, the investigators noted that a phase 1/2 trial (NCT05795595) of CTX131, which builds on CTX130 with CRISPR edits to enhance potency and persistence, is currently enrolling patients.

The study authors plan to enroll 250 adult patients with relapsed or refractory solid tumors across clinical trial sites in the US. The primary end points for the trial are the incidence of AEs and objective response rate per RECIST v1.1. Study completion is expected in 2030.5

References

1. Srour SA,Tran B, Haanen JB, et al. CT002 - CTX130 allogeneic CRISPR-Cas9-engineered chimeric antigen receptor (CAR) T cells in patients with advanced clear cell renal cell carcinoma: Long-term follow-up and translational data from the phase 1 COBALT-RCC study. Presented at: 2024 American Association for Cancer Research Annual Meeting. San Diego, California. April 5-10, 2024. Abstract CT002

2. Pal SK, Tran B, Haanen JBAG, et al. CD70-Targeted Allogeneic CAR T-Cell Therapy for Advanced Clear Cell Renal Cell Carcinoma. Cancer Discov. 2024 Apr 5:OF1-OF14. doi:10.1158/2159-8290.CD-24-0102

3. ACR: Novel immunotherapies show promise for patients with kidney cancer and for solid organ transplant recipients with skin cancer. News release. University of Texas MD Anderson Cancer Center. April 4, 2024. Accessed April 10, 2024. https://www.newswise.com/articles/aacr-novel-immunotherapies-show-promise-for-patients-with-kidney-cancer-and-for-solid-organ-transplant-recipients-with-skin-cancer

4. A safety and efficacy study evaluating CTX130 in subjects with relapsed or refractory renal cell carcinoma (COBALT-RCC). ClinicalTrials.gov. Last updated May 11, 2023. Accessed April 10, 2024. https://clinicaltrials.gov/study/NCT04438083

5. A safety and efficacy study evaluating CTX131 in adult subjects with relapsed or refractory solid tumors. ClinicalTrials.gov. Last updated April 2, 2024. Accessed April 10, 2024. https://clinicaltrials.gov/study/NCT05795595

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