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CTX130 Shows Acceptable Safety Profile, Clinically Meaningful Responses in R/R T-Cell Lymphoma

CTX130 is also being investigated for the treatment of r/r renal cell carcinoma in a phase 1 clinical trial called COBALT-RCC (NCT04438083).

CTX130, a first-in-class CD70-targeting allogeneic CAR-T therapy, was shown to have an acceptable safety profile and to produce clinically meaningful responses in patients with heavily pretreated relapsed/refractory (r/r) T-cell lymphoma (TCL), according to findings from COBALT-LYM (NCT04502446), an ongoing global, multicenter, phase 1 clinical trial.1 The findings were presented at the 2022 European Hematology Association Annual Meeting, June 9-17, 2022, in Vienna, Austria and virtual.

Among the 18 patients who had received 1 of 4 dose levels (DL) of CTX130 (DL1, 3x107; DL2, 1x108; DL3, 3x108; DL4, 9x108) with at least 28 days of follow-up, there were no cases of graft versus host disease nor any instances of tumor lysis syndrome, and no dose-limiting toxicities.2

In terms of clinical responses, a higher percentage of patients responded at higher dose levels, with the overall response rate in DL3 and higher (n=10) being 70%, with 30% of these patients achieving complete remission and 40% achieving a partial response. Furthermore, 90% of patients who received DL3 or higher experienced some clinical benefit, which the investigators defined as stable disease or better response.

Based on these results, the investigators concluded that CTX130 has an acceptable safety profile in patients with heavily pretreated r/r TCL and has the potential to provide clinically meaningful benefit.

"We are very pleased with the preliminary results from our COBALT-LYM trial, which showed efficacy and safety that suggest that CTX130, the first allogeneic CAR-T directed against the novel target CD70, can produce deep responses in patients with relapsed or refractory T cell lymphomas," said Samarth Kulkarni, PhD, chief executive officer, CRISPR Therapeutics, in a statement.2 "Additionally, we may be able to further optimize the profile by continuing our consolidation dosing strategy. These data reinforce our belief that engineered cell therapies are the future in our fight against cancer and we are well-positioned to be leaders in this field."

As of December 2021, the ages of the patients enrolled in the study ranged from 39 to 78 (median, 67). All patients had been heavily pretreated with systematic therapies (median, 4) and all patients were refractory to their most recent line of therapy. The study included 8 patients with peripheral TCL and 10 patients with cutaneous TCL. Patients who had previously been treated with any CD70-targeting agents were excluded from participation in the study.

Adverse events included infections, cytokine release syndrome (CRS), and immune effector cell-associated neurotoxicity syndrome (ICANS). However, all cases of CRS and ICANS were grades 1 or 2 and either required no specific intervention or resolved following standard CRS management, and neither the frequency nor severity of CRS increased in patients after being redosed with CTX130. Of note, 1 death occurred but was deemed unrelated to the study drug, and there were no treatment-related deaths during the trial.

"While overall survival in a subset of patients with T cell lymphoma has improved with front-line combination chemotherapy, relapsed or refractory patients continue to have very limited treatment options," said Swaminathan P. Iyer, MD, professor, lead of the T Cell Lymphoma Program, Department of Lymphoma/Myeloma, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, in a statement.2 "The data from the CTX130 trial demonstrate the potential of cell therapies as a new treatment modality for these patients. I am particularly encouraged by the response rates and safety data, which suggest that treatment with CTX130 could elicit clinically meaningful responses, including complete responses, in patients with difficult-to-treat T cell lymphomas."

In addition to the COBALT-LYM study, CTX130 is also being investigated for the treatment of r/r renal cell carcinoma in a phase1 clinical trial called COBALT-RCC (NCT04438083).

REFERENCES
1. Iyer SP, Sica RA, Ho PJ, et al. The COBALT-LYM study of CTX130: a phase 1 dose escalation study of CD70-targeted allogeneic CRISPR-Cas9–engineered CAR T cells in patients with relapsed/refractory (r/r) T-cell malignancies. Presented at: 2022 Hybrid Congress of the European Hematology Association (EHA). June 9-12, 2022; Vienna, Austria. Abstract #S262
2. CRISPR Therapeutics presents positiveresults from its phase 1 COBALT-LYM trial of CTX130 in relapsed or refractory T cell malignancies at the 2022 European Hematology Association (EHA) Congress. News release. CRISPR Therapeutics. June 12, 2022. https://firstwordpharma.com/story/5593297