BCMA-directed CAR-T Gets IND Clearance for R/R Multiple Myeloma

IASO Biotherapeutics’ equecabtagene autoleucel (CT103A), an investigational autologous chimeric antigen receptor T-cell (CAR-T) therapy being developed for the treatment of relapsed/refractory (r/r) multiple myeloma (MM), has received clearance of its investigational new drug (IND) application from the FDA.¹

CT103A targets B-cell maturation antigen (BCMA). It contains a fully human single-chain variable fragment (scFv), which is intended to allow the therapy to bypass anti-CAR immunogenicity without the loss of anti-tumor activity. In June of 2022, a new drug application (NDA) for CT103A for the treatment of r/r MM was accepted by China’s National Medical Products Administration (NMPA).² CT103A also received clearance of an IND application from the NMPA for an expanded indication in neuromyelitis optica spectrum disorder (NMOSD) in August 2022.³

"The IND approval of CT103A in the United States is an important milestone of IASO Bio and a new starting point outside China,” Wen (Maxwell) Wang, chief executive officer, IASO Bio, said in a statement regarding the news.¹ “IASO Bio will accelerate its overseas clinical trials and the development and implementation of cellular immunotherapy drugs to benefit more patients globally."

CT103A is currently being evaluated in China for the treatment of r/r MM in the phase 1/2 FUMANBA-1 (NCT05066646) clinical trial. Data from the trial presented at the European Hematology Association (EHA) Research Conference 2022 indicated that as of the January 21, 2022, data cut-off, the objective response rate (ORR) was 94.9% with a median follow-up of 9 months (range, 1.2 to 19.6) in 79 patients across 14 clinical centers who received the recommended phase 2 dose of 1.0×10⁶ CAR-T cells/kg. The patients additionally showed a median time to response of 16 days, and 92.4% of the participants achieved negative minimal residual disease (MRD) status at least once following treatment. It was noted that all patients who showed a complete response or better achieved MRD-negative status. It was also noted that participants who had previously received CAR-T therapy benefitted from CT103A. In terms of safety, all cases of cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) were grade 1 to grade 2 and resolved with supportive treatment.

CT103A previously received breakthrough therapy designation for r/r MM from the NMPA in February 2021 and orphan drug designation for MM from the FDA in February 2022.¹ In addition to FUMANBA-1, CT103A is also being investigated in a phase 1 clinical trial (NCT05201118) in combination with Selinexor for the treatment of patients with r/r extramedullary MM in China. A phase 1 clinical trial (FUMANBA-2; NCT05181501) for patients in China with newly diagnosed high-risk MM is planned, but the initiation of recruitment has not yet been announced.

“At the 63rd Annual Meeting of ASH in 2021, we reported the results of the clinical study on CT103A injection...” principal investigators Lugui Qiu, MD, the Chinese Academy of Medical Science Hematology Hospital, and Chunrui Li, MD, PhD, Tongji Hospital, Tongji Medical College, Huazhong University of Science & Technology, said in a joint statement in June 2022.² "These study results showed that CT103A has excellent safety and efficacy profiles. In addition, CT103A also demonstrated favorable efficacy in patients with extramedullary multiple myeloma and patients who had received prior CAR-T therapy. These results suggest that CT103A is potentially a new and effective immunotherapy treatment option for patients with MM.”

REFERENCES

1. IASO Bio announces US FDA approval of clinical trial application for BCMA CAR-T CT103A for relapsed/refractory multiple myeloma. News release. IASO Biotherapeutics. December 22, 2022.http://www.iasobio.com/info.php?id=209 

2. IASO Bio and Innovent jointly announce the NMPA acceptance of the new drug application for equecabtagene autoleucel for the treatment of relapsed and/or refractory multiple myeloma. News release. IASO Biotherapeutics. June 2, 2022. http://www.iasobio.com/info.php?id=190 

3. World's first CAR-T for NMOSD treatment, IASO Biotherapeutics' equecabtagene autoleucel, receives IND approval by NMPA. News release. IASO Biotherapeutics. August 19, 2022. http://www.iasobio.com/info.php?id=198