On September 21, 2022 CARsgen Therapeutics Holdings Limited (Stock Code: 2171.HK), a company focused on innovative CAR T-cell therapies for the treatment of hematologic malignancies and solid tumors, reported that at the 7th Annual CAR-TCR Summit, in Boston, Massachusetts, the Company gave an oral presentation on the North America Phase 2 clinical trial of zevorcabtagene autoleucel ("zevor-cel", R&D code: CT053), an autologous CAR T-cell product candidate against BCMA (Press release, Carsgen Therapeutics, SEP 21, 2022, View Source [SID1234621316]). This multi-center, open-label, Phase 1b/2 study (NCT03915184) is being conducted to evaluate the safety and efficacy in North American patients with relapsed and/or refractory multiple myeloma (R/R MM).
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As of August 31, 2022, 17 patients with R/R MM received zevor-cel infusion in the Phase 2 portion of the clinical trial and have been followed for a median of 113 days (range: 9 to 373). Of these 17 patients, five patients (29.4%) had extramedullary disease (EMD; ≥1 plasmacytoma) and nine patients (52.9%) had high-risk cytogenetic features. Patients were heavily pretreated with a median of six prior lines of therapy (range: 4 to 17). All patients were refractory to their last line of therapy. Prior to zevor-cel infusion, patients received lymphodepletion regimen of fludarabine (30mg/m2 for three consecutive days) and cyclophosphamide (500mg/m2 for two consecutive days).
Efficacy
In the 11 evaluable patients who had at least eight weeks follow-up, including four patients with EMD, the objective response rate was 100% (very good partial response, complete response, or stringent complete response) and responses deepened for patients with longer follow-up. Since all responses are ongoing, the median progression-free survival, median overall survival and median duration of response have not been reached, and the complete response/stringent complete response rate is not mature. All patients with available MRD results at week 4 were MRD negative by next-generation of sequencing.
Safety
No death occurred and no patient experienced Grade 3 or higher cytokine release syndrome. Cytokine release syndrome was observed in 10 of 17 patients (59%), all reported as Grade 1 or 2. One transient Grade 3 immune effector cell-associated neurotoxicity syndrome event was reported and the patient fully recovered; no neurological toxicity with parkinsonian features was observed. For the management of post-infusion symptoms, five of 17 patients (29%) received tocilizumab and one patient (5.9%) received corticosteroids. Notably, three patients have received outpatient zevor-cel treatment in this study, and the two patients were admitted into the hospital for symptom management for 1 or 2 days.
Conclusion
Zevor-cel at a dose of 1.8×108 CAR T cells was well tolerated in the initial 17 Phase 2 patients with R/R MM, with promising efficacy and MRD negativity. Outpatient treatment is currently undergoing further exploration.
Dr. Raffaele Baffa, Chief Medical Officer of CARsgen Therapeutics, said: "Multiple myeloma is the second most common hematologic malignancy. People in the United States (US) living with or in remission from multiple myeloma is expected to increase to about 160 thousand in 2024. There remains a significant unmet medical need of multiple myeloma patients that call for alternative options. The results of the initial 17 patients treated with zevor-cel in the LUMMICAR-2 Phase 2 clinical trial, reported at the CAR-TCR Summit, indicates a consistent trend of clinical benefit with the data of earlier trials conducted on zevor-cel, such as the investigator-initiated trials and LUMMICAR-1 phase 1 trials in China as reported previously in ASH (Free ASH Whitepaper). We are very encouraged by the competitive efficacy and favorable safety profiles and will continue to dedicate our efforts in successfully developing and launching zevor-cel for multiple myeloma patients worldwide."
About Zevor-cel
Zevor-cel (CT053) is a fully human, autologous BCMA CAR T-cell product candidate for the treatment of R/R MM. CARsgen is conducting a Phase 1b/2 clinical trial (LUMMICAR STUDY 2) in North America to evaluate the safety and efficacy of zevor-cel for R/R MM. The Company also plans to conduct additional clinical trials to develop zevor-cel as an earlier line of treatment for multiple myeloma.
Zevor-cel received Regenerative Medicine Advanced Therapy (RMAT) and Orphan Drug designations from the U.S. Food and Drug Administration (FDA) in 2019, as well as the PRIority MEdicines (PRIME) and Orphan Medicinal Product designations from the European Medicines Agency (EMA) in 2019 and 2020, respectively. Zevor-cel also received Breakthrough Therapy designation from the NMPA in 2020.
The Company believes that zevor-cel is well positioned to potentially reshape the treatment paradigm for multiple myeloma and become a foundational treatment for multiple myeloma patients.