Third CAR T cell therapy – Fucaso (Equecabtagene Autoleucel) approved in China for relapsed/Refractory Multiple Myeloma

China’s National Medical Products Administration (NMPA) has approved the new drug application for equecabtagene autoleucel (Fucaso) for the treatment of adult patients with relapsed or refractory multiple myeloma who previously received 3 or more lines of therapy, including a proteasome inhibitor and an immunomodulatory drug.

NMPA has approved the new drug application for Fucaso for the treatment of adult patients with relapsed or refractory multiple myeloma who previously received 3 or more lines of therapy, including a proteasome inhibitor (PI) and an immunomodulatory drug (IMiD).1

The application was supported by findings from the phase 1/2 FUMANBA-1 trial (NCT05066646; CTR20192510), in which the BCMA-targeted CAR T-cell therapy elicited an overall response rate of 96% in all evaluable patients (n = 101); this included a complete response (CR) or higher rate of 74.3% and a very good partial response or higher rate of 91.1%.2

In the 89 patients who had not received prior CAR T-cell therapy (n = 89), the ORR achieved with equecabtagene autoleucel was 98.9%, with 78.7% of patients experiencing a CR or better. In the 12 patients who had prior exposure to this modality, the agent induced an ORR of 75%, with a stringent CR (sCR) experienced by 41.7% of patients. Notably, 4 patients who achieved a sCR had a sustained response for 18 months following infusion.

“There’s a significant unmet clinical need for the treatment of multiple myeloma in China,” Professor Lugui Qiu, MD, of the Chinese Academy of Medical Science Hematology Hospital, and Professor Chunrui Li, MD, PhD, of the Tongji Hospital, Tongji Medical College, Huazhong University of Science & Technology, stated in a press release.“As a fully-human BCMA CAR [T-cell] therapy, Fucaso has demonstrated remarkable efficacy, with evidence of deep and durable response for high-quality survival for [patients with] multiple myeloma. We believe that Fucaso’s approval will offer clinicians a novel breakthrough option benefitting patients with later-line relapsed or refractory multiple myeloma.”

FUMANBA-1 enrolled patients with relapsed or refractory multiple myeloma who previously received at least 3 prior therapies, including a PI and an IMiD.2 Patients needed to be refractory to their last line of treatment. Notably, those who had received prior BCMA-targeted CAR T-cell therapies and experienced disease progression were permitted.

Patients were screened and then underwent apheresis and received bridging therapy, as needed. Lymphodepleting chemotherapy was comprised of cyclophosphamide at 500 mg/m2 plus fludarabine at 30 mg/m2 for 3 consecutive days between day -7 and -2. All participants then received a single infusion of equecabtagene autoleucel at a dose of 1.0 x 106 CAR T cells/kg.

The key objectives of the trial were to examine the safety, efficacy, pharmacokinetics, and pharmacodynamics of the product in this population. Assessments will be conducted from day 1 up to 2 years after the infusion, and long-term follow-up will continue for a maximum of 15 years.

At the time of the data cutoff date of September 9, 2022, 103 patients had received the CAR T-cell therapy on the study; 17 patients received treatment in phase 1 and the remainder received treatment in phase 2. The median follow-up time was 13.8 months (range, 0.4-27.2).

The median age of the 103 patients was 58 years (range, 39-70) and 53.4% of patients were male. Most patients (99.0%) of patients were Chinese and had an ECOG performance status of 1 (76.7%). Moreover, 12.6% of patients had extramedullary disease. The median months since diagnosis in these patients was 43.4 months (range, 6.6-193.2).

Moreover, the median number of prior lines of therapy received was 4, with a range of 3 to 23 lines. All patients were double-class exposed, and 20.4% were triple-class exposed. All patients received prior PIs and glucocorticoids, and 98.1% received prior IMiDs. Most (93.2%) had been exposed to chemotherapy, 11.7% had exposure to CAR T-cell therapies, 20.4% had prior monoclonal antibodies, and 27.2% previously underwent stem cell transplant. The median follow-up after infusion was 13.8 months (range, 0.4-27.2).

Additional data presented at the 2023 ASCO Annual Meeting showed that the median time to first response with the agent was 16 days (range, 11-179) and the median duration of response was not yet reached. The median progression-free survival (PFS) with equecabtagene autoleucel was also not reached. The 12-month PFS rates were 78.8% (95% CI, 68.6%-85.97%), 89.5% (95% CI, 79.06%-94.85%), and 84.4% (95% CI, 73.94%-90.88%) for all patients, those who achieved a CR or better, and those who previously received CAR T-cell therapy, respectively.

Moreover, 82.4% of patients achieved minimal residual disease (MRD) negativity that was sustained for longer than 12 months. The median time to MRD-negative status was 2 weeks (range, 13 days-185 days). Those who had sustained MRD-negative status over 12 months experienced a 12-month PFS rate of 100% (95% CI, 100%-100%).

Regarding safety, 93.2% of patients experienced cytokine release syndrome (CRS), with most cases grade 1 or 2 in severity. Of the 96 patients who had this toxicity, 67.7% received glucocorticoids and 31.3% received tocilizumab (Actemra); 75% received both.

Additionally, 1.9% of patients experienced grade 1 or 2 immune effector cell–associated neurotoxicity syndrome. The time to first onset of this toxicity was 6.5 days (range, 3-10) and the median duration was 1.5 days (range, 1-2)

The most common toxicities that were grade 3 or higher and related to treatment were hematologic.

In 12- and 24-month follow-ups after infusion, equecabtagene autoleucel was noted to still be detectable in 50% and 40% of patients, respectively.Moreover, under 20% (19.4%) of patients were positive for antidrug antibodies post infusion.



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