Zevor-Cel Yields 100% ORR in R/R Multiple Myeloma
Eleven patients in the LUMMICAR-2 trial were evaluable for preliminary efficacy analyses.
Zevorcabtagene autoleucel (zevor-cel; CARsgen; CT053) yielded a 100% overall response rate (ORR) in patients with relapsed/refractory multiple myeloma (R/R MM) enrolled in the phase 1b/2 LUMMICAR-2 study (NCT03915184).
Data from the study were presented at the 7th Annual CAR-TCR Summit, in Boston, Massachusetts, on September 20-22. The multicenter, open-label study is evaluating zevor-cel, an autologous chimeric antigen receptor (CAR) T-cell therapy, in patients across North America.
“Multiple myeloma is the second most common hematologic malignancy. People in the 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,” Raffaele Baffa, MD, PhD, chief medical officer, CARsgen Therapeutics, said in a statement.
Seventeen patients with R/R MM have been treated with 1.8×108 zevor-celcells in the phase 2 portion of the trial as of August 31, 2022. Patients were followed up for a median of 113 days (range, 9-373). Five patients (29.4%) had extramedullary disease (EMD; ≥1 plasmacytoma and 9 (52.9%) had high-risk cytogenic features. Patients were refractory to their last line of therapy and were heavily pretreated, with a median of prior lines of therapy (range, 4-17). They received a lymphodepletion regimen of fludarabine (30mg/m2 for 3 consecutive days) and cyclophosphamide (500mg/m2 for 2 consecutive days) prior to zevor-cel infusion.
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Zevor-cel was well-tolerated, with no patient deaths and no grade 3 or higher cytokine release syndrome (CRS). Three patients were infused in an outpatient setting and 2 were admitted to the hospital for symptom management for 1 or 2 days. Outpatient administration is continuing to be explored in trial participants. Grade 1 or 2 cases of CRS were observed in 10 patients (59%). There was 1 case of grade 3 transient immune effector cell-associated neurotoxicity syndrome in which the patient fully recovered with no neurological toxicity or parkinsonian features. Five patients (29%) received tocilizumab and 1 (5.9%) received corticosteroids to manage post-infusion symptoms.
Eleven patients were evaluable for efficacy with at least 8 weeks of follow-up. The ORR was 100% in these patients, 4 of which had EMD, including very good partial response, complete response (CR), or stringent CR. Responses deepened in patients with longer follow-up. Median progression-free survival, median overall survival and median duration of response have not yet been reached and CR and stringent CR is not yet final. Investigators also conducted next-generation sequencing and found that all patients with minimal residual disease (MRD) results at week 4 were MRD-negative.
“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. 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,” Baffa added.
