Zevorcabtagene Autoleucel Wins Approval in China for R/R Multiple Myeloma

China’s NMPA has approved zevor-cel for the treatment of adult patients with relapsed/refractory multiple myeloma after at least 3 lines of therapy.

China’s National Medical Products Administration (NMPA) has approved the autologous CAR T-cell therapy zevorcabtagene autoleucel (zevor-cel; CT053) for the treatment of adult patients with relapsed/refractory multiple myeloma whose disease progressed after at least 3 lines of therapy, including a proteasome inhibitor (PI) and an immunomodulatory drug (IMiD).1

The regulatory decision was supported by data from the phase 1/2 LUMMICAR STUDY 1 trial (NCT03975907), which showed that at a median follow-up of 37.7 months (range, 14.8-44.2), evaluable patients treated with the BCMA-targeted CAR T-cell therapy (n = 14) achieved an overall response rate (ORR) of 100% and a complete response (CR)/stringent CR (sCR) rate of 78.6%.2 Notably, all patients who experienced a CR/sCR achieved minimal residual disease negativity.

“In the realm of traditional treatments, the prognosis for patients dealing with relapsed or refractory multiple myeloma remains notably grim, given the limitations of available therapeutic alternatives,” Wenming Chen, MD, PhD, principal investigator of LUMMICAR STUDY 1 and director of the Hematology Department at Beijing Chao-Yang Hospital of Capital Medical University in China, stated in a news release. “These individuals confront substantial unmet clinical needs, necessitating an expeditious adoption of an effective, safe, and convenient treatment modalities. The approval of zevor-cel not only expands the array of choices available to clinical practitioners but also brings new hope to patients.”

LUMMICAR STUDY 1 was an open-label, multicenter trial that evaluated zevor-cel in patients at least 18 years of age and no older than 75 years of age with relapsed/refractory multiple myeloma.3 At least 3 prior lines of treatment were required, including at least 1 PI and 1 IMiD. Disease relapse within 12 months following the last line of therapy or disease progression within 60 days of the last line of therapy were required. Other key inclusion criteria included having a life expectancy of more than 12 weeks, an ECOG performance status of 0 or 1, and adequate organ function.

The study excluded patients who received any prior CAR T-cell therapy, those treated with a prior BCMA-directed therapy, and patients who underwent prior allogeneic stem cell transplant for multiple myeloma. Autologous stem cell transplant less than 12 weeks prior to leukapheresis was not permitted.

One to 2 days following the completion of lymphodepletion, patients received a single infusion of zevor-cel. Of the 14 evaluable patients at the most recent data cutoff date of July 17, 2023, 3 received the CAR T-cell therapy at 1.0 x 108 CAR+ T cells, and 11 patients were administered an infusion of 1.5 x 108 CAR+ T cells.2

Dose-limiting toxicities served as the primary end point in phase 1, and ORR was the primary end point of phase 2. Secondary end points included MRD negativity, time to response, CR/sCR rate, ORR at week 12, clinical benefit rate, safety, and pharmacokinetics.3

Patients evaluable for efficacy had a median age of 54 years (range, 34-62), and half had high-risk cytogenetic abnormalities. Notably, 14.3% had extramedullary disease, and 14.3% had stage III disease per the International Staging System.2

Regarding safety, no instances of grade 3 or higher cytokine release syndrome or any-grade immune effector cell–associated neurotoxicity were observed. Three patients experienced treatment-related grade 3 infections. Serious adverse effects (AEs) occurred in 3 patients, including 2 patients who experienced serious treatment-related AEs in the form of pulmonary infection and tumor lysis syndrome. Two deaths were reported, although neither was deemed related to zevor-cel.

“Based on the published results of the LUMMICAR-1 study, zevor-cel has demonstrated profound and enduring therapeutic efficacy in patients with relapsed or refractory multiple myeloma, exhibiting overall favorable tolerability,” Chengcheng Fu, MD, PhD, principal investigator of LUMMICAR STUDY 1 and director of the Hematology Department at the First Affiliated Hospital of Soochow University, stated in a news release.1 “We are pleased to witness the regulatory approval and market launch of zevor-cel. We look forward to its potential to benefit a larger number of individuals, aiding them in achieving high-quality, long-term survival.”

Zever-cel is also being investigated in North America in the phase 2 the phase 2 LUMMICAR-2 trial (NCT03915184), and previously reported results showed that 11 evaluable patients experienced an ORR of 100%, with all achieving a very good partial response or better.4

References

  1. 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 March 1, 2024. https://www.carsgen.com/en/news/20240301/
  2. CARsgen presents updated research results on zevor-cel at 2023 ASH Annual Meeting. News release. CARsgen Therapeutics. December 12, 2023. Accessed March 1, 2024. https://www.carsgen.com/en/news/20231212/
  3. Clinical trial to evaluate CT053 in patients with relapsed and/or refractory multiple myeloma (LUMMICAR STUDY 1). ClinicalTrials.gov. Updated February 28, 2024. Accessed March 1, 2024. https://classic.clinicaltrials.gov/ct2/show/NCT03975907
  4. 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 March 1, 2024. https://www.carsgen.com/en/news/20220921/