Long-Term Data Affirm Efficacy of Zevor-Cel in R/R Myeloma

Treatment with the BCMA-targeted CAR T-cell therapy zevorcabtagene autoleucel (zevor-cel; CT053) led to durable responses in patients with relapsed/refractory multiple myeloma who had received at least 3 prior lines of therapy, according to long-term data from the phase 1 portion of the LUMMICAR Study 1 (NCT03975907) published in Blood Advances.¹

At a median follow-up of 53.3 months (range, 14.8-63.5), evaluable patients across 2 dose levels (n = 14) achieved an overall response rate (ORR) of 100% (95% CI, 76.8%-100%), including a complete response (CR)/stringent CR (sCR) rate of 78.6% (95% CI, 49.2%-95.3%). The very good partial response (VGPR) or better rate was 92.9% (95% CI, 66.1%-99.8%).

At a dose of 100 x 10⁶ chimeric antigen receptor (CAR) T cells (n = 3), zevor-cel generated CR/sCR and VGPR or better rates of 66.7% (95% CI, 9.4%-99.2%) and 100% (95% CI, 29.2%-100%), respectively. In patients dosed with 150 x 106 CAR T cells (n = 11), the respective rates were 81.8% (95% CI, 48.2%-97.7%) and 90.9% (95% CI, 58.7%-99.8%).

The median duration of response (DOR) for the overall population was 24.9 months (95% CI, 14.0-45.9). The median DORs were not evaluable (NE; 95% CI, 2.8-NE) at the 100 x 10⁶ CAR T-cell dose and 23.9 months (95% CI, 14.0-NE) at the 150 x 10⁶ CAR T-cell dose. For patients who achieved a CR or better, the median DOR was 43.2 months (95% CI, 14.6-NE) in the overall population, NE (95% CI, NE-NE) at the 100 x 10⁶ CAR T-cell dose, and 26.0 months (95% CI, 14.2-NE) at the 150 x 10⁶ CAR T-cell dose.

“Zevor-cel demonstrates compelling antitumor activity without conferring any safety disadvantages as evidenced by the lack of higher-grade cytokine release syndrome [CRS] or neurotoxicity,” lead study author Chengcheng Fu, MD, PhD, of the National Clinical Research Center for Hematologic Diseases of the Jiangsu Institute of Hematology at the First Affiliated Hospital of Soochow University in Suzhou, China, and colleagues wrote in the publication. “However, as in phase 1 clinical trials, the limited sample size of this study may not adequately characterize the safety profile of zevor-cel. We aim to address these limitations by expanding the sample size, increasing the diversity and representativeness of the trial, and improving the generalizability of the data through multicenter phase 2 clinical trials, [including the phase 2 portion of] LUMMICAR [study 1] in China and [the] LUMMICAR study 2 [NCT03915184] in the United States and Canada.”

In March 2024, China’s National Medical Products Administration (NMPA) approved zevor-cel for the treatment of adult patients with relapsed/refractory multiple myeloma whose disease has progressed after at least 3 lines of therapy, including a proteasome inhibitor (PI) and an immunomodulatory drug (IMiD), based on prior data from LUMMICAR Study 1.²

How was the phase 1 portion of LUMMICAR designed?

LUMMICAR is an ongoing, single-arm, open-label, multicenter phase 1/2 trial.¹ In the phase 1 portion of the study, investigators enrolled patients 18 to 75 years of age with relapsed/refractory multiple myeloma who had received at least 3 prior lines of therapy, including a PI and an IMiD; relapsed within 12 months of their last line of therapy; or experienced disease progression within 60 days of their last line of therapy.

Other key inclusion criteria comprised measurable disease, an ECOG performance status of 0 or 1, adequate organ function, and a life expectancy of at least 12 weeks. Prior treatment with a BCMA-directed therapy or any CAR T-cell therapy was not permitted.

Following leukapheresis, bridging therapy was permitted before lymphodepletion if clinically indicated. Lymphodepletion comprised fludarabine at 25 mg/m² and cyclophosphamide at 300 mg/m² per day on days –5 to –3. Zevor-cel was then administered at a dose of 100 x 10⁶ or 150 x 10⁶ CAR T cells.

Safety and tolerability of zevor-cel in the first 28 days following infusion served as the trial’s primary end point. Secondary end points included overall safety and tolerability, efficacy, and pharmacokinetics.

The overall population from phase 1 had a median age of 54.0 years (range, 34-62), half the patients were female, and half the patients had an ECOG performance status of 0. The median time from diagnosis to screening was 4.70 years (range, 1.2-8.7). Half the patients had high-risk disease, and International Staging System stages included I (35.7%), II (50.0%), and III (14.3%). Additionally, 14.3% of patients had extramedullary disease. The median number of prior lines of therapy was 6.0 (range, 3-11).

What additional efficacy and safety data were reported for zevor-cel with long-term follow-up?

In the overall population, the median progression-free survival (PFS) was 25.8 months (95% CI, 14.9-46.7); the 36- and 48-month PFS rates were 41.7% (95% CI, 16.4%-65.4%) and 15.6% (95% CI, 1.2%-46.2%), respectively. The median PFS for patients who achieved CR/sCR was 44.1 months (95% CI, 15.5-NE).

The median overall survival (OS) was NE (95% CI, 48.5-NE); the 36-, 48-, and 60-month OS rates were 92.3% (95% CI, 56.6%-98.9%), 84.6% (95% CI, 51.2%-95.9%), and 76.9% (95% CI, 44.2%-91.9%), respectively.

Regarding safety, no dose-limiting toxicities were reported during the study. CRS was reported in 92.9% of patients, but all instances were grade 1 or 2. The median time to CRS onset was 6 days (range, 2-12), and all CRS resolved at a median time of 4 days (range, 2-20). No instances of immune effector cell–associated neurotoxicity syndrome were reported.

All patients experienced grade 3 or 4 treatment-emergent adverse effects, with the most common including decreased lymphocyte count (100%), decreased neutrophil count (100%), decreased white blood cell count (100%), decreased platelet count (92.9%), pyrexia (35.7%), and anemia (35.7%).

References

1. Fu C, Chen W, Cai Z, et al. Long-term follow-up of zevor-cel in patients with relapsed/refractory multiple myeloma. Blood Adv. 2026;10(2):468-478. doi:10.1182/bloodadvances.2025017365
2. NMPA approves the NDA for CARsgen’s BCMA CAR-T therapy zevorcabtagene autoleucel for relapsed or refractory multiple myeloma. News release. CARsgen Therapeutics. March 1, 2024. Accessed April 9, 2026. https://www.carsgen.com/en/news/20240301/