Zevor-cel Elicits 100% ORR in Heavily Pretreated Relapsed/Refractory Myeloma

Raffaele Baffa, MD, PhD

The BCMA-directed CAR T-cell therapy zevorcabtagene autoleucel (zevor-cel; CT053) demonstrated a 100% objective response rate (ORR) in heavily pretreated patients with relapsed/refractory multiple myeloma, according to data from the phase 2 LUMMICAR-2 trial (NCT03915184).¹

Findings presented at the 7th Annual CAR-TCR Summit showed that among 11 patients with at least 8 weeks of follow-up, all experienced a stringent complete response (sCR), complete response (CR), or very good partial response. Notably, data on the sCR and CR rates are not mature.

At the August 31, 2022, data cutoff, all responses were ongoing. Therefore, the median duration of response, progression-free survival, and overall survival have not yet been reached. All patients evaluable for minimal residual disease (MRD) were MRD negative at week 4.

“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, indicate a consistent trend of clinical benefit with the data of earlier trials conducted on zevor-cel, such as the investigator-initiated trials and [phase 1] LUMMICAR-1 trial [NCT03975907],” Raffaele Baffa, MD, PhD, chief medical officer of CARsgen Therapeutics, stated in a press release.

“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.

Zevor-cel is a fully human, autologous BMCA CAR T-cell therapy. In October 2019, the FDA granted a Regenerative Medicine Advanced Therapy designation to zevor-cel for the treatment of patients with relapsed/refractory multiple myeloma.²

LUMMICAR-2 enrolled patients who were at least 18 years old and less than 80 years old with relapsed/refractory multiple myeloma who received prior treatment with at least one proteasome inhibitor, one immunomodulatory drug, and one CD38 antibody.³ Patients were also required to be refractory to their last line of therapy, have measurable disease, have a life expectancy of more than 12 weeks, and have an ECOG performance status of 0 or 1.

Key exclusion criteria included prior anti-BCMA therapy; graft-vs-host disease; stem cell transplant within one year prior to leukapheresis; HIV, active hepatitis C virus, or active hepatitis B virus infection; any uncontrolled active infection; or unresolved adverse effects from prior treatments.

Enrolled patients received leukapheresis to collect autologous mononuclear cells to manufacture zevor-cel. Patients then underwent lymphodepletion with 30 mg/m² of fludarabine for 3 consecutive days and 500 mg/m² of cyclophosphamide for 2 consecutive days before receiving 1 infusion of zevor-cel at 1.8 x 10⁸ CAR T cells

As of data cutoff, 17 patients received a zevor-cel infusion during the phase 2 portion of the trial and were followed for a median of 113 days (range, 9-373). Notably, 5 patients had extramedullary disease, and 9 patients had high-risk cytogenetics. The median number of prior lines of therapy was 6 (range, 4-17).

Regarding safety, no instances of grade 3 or higher cytokine release syndrome (CRS) were reported. Ten of 17 patients experienced grade 1 or 2 CRS. One patient had grade 3 immune effector cell–associated neurotoxicity syndrome and fully recovered. No instances of parkinsonian features were reported. Five patients were given tocilizumab (Actemra) and 1 patient received corticosteroids to manage post-infusion symptoms.

Three patients received zevor-cel as outpatient treatment as part of the study. Two were admitted to the hospital for symptom management for 1 to 2 days.

Future clinical trials are being planned to evaluate zevor-cel in earlier treatment lines of multiple myeloma.

References

1. CARsgen presents North America phase 2 updates for CT053 BCMA CAR T at the 7th annual CAR-TCR summit. News release. CARsgen Therapeutics. September 21, 2022. Accessed September 21, 2022. https://bit.ly/3f2lzjz
2. CARsgen announces investigational CAR-T therapy CT053 granted RMAT designation by the U.S. FDA for R/R multiple myeloma. News release. CARsgen Therapeutics. October 28, 2019. Accessed September 21, 2022. https://prn.to/3DDYy0O
3. Clinical trial to evaluate zevor-cel (CT053) in patients with relapsed and/or refractory multiple myeloma (LUMMICAR STUDY 2). ClinicalTrials.gov. Updated July 19, 2022. Accessed September 21, 2022. https://clinicaltrials.gov/ct2/show/NCT03915184