CAR-T CT103A Demonstrates Deep Responses in R/R Multiple Myeloma

Article

Among 101 patients included in the efficacy analysis, the ORR was 96% and the CR rate was 74.3%.

Equecabtagene autoleucel (CT103A), an investigational autologous chimeric antigen receptor T-cell (CAR-T) therapy being developed in a collaboration between Innovent and IASO Bio, has demonstrated deep responses and a favorable safety profile in patients with relapsed/refractory (r/r) multiple myeloma (MM), according to results from the phase 1b/2 FUMANBA-1 clinical trial (NCT05066646; ChiCTR1800018137) presented in a poster at the American Society of Clinical Oncology (ASCO) 2023 Annual Meeting, held June 2-6, in Chicago, Illinois.1

CT103A targets B-cell maturation antigen and contains a fully human single-chain variable fragment antibody, which is intended to allow the therapy to bypass antiCAR immunogenicity without the loss of antitumor activity.2 Among 101 patients from FUMANBA-1 who were included in the efficacy analysis, the overall response rate (ORR) was 96%, the complete response (CR) rate was 74.3%, and the very good partial response rate was 91.1%.1

Among a subset of 89 patients who had not previously received treatment with a CAR-T therapy for their disease, the ORR was 98.9% and the CR/stringent CR (sCR) rate was 78.7%. First author Chunrui Li, MD, PhD, of Tongji Hospital, Tongji Medical College, Huazhong University of Science & Technology, and colleagues noted that in this group, the sCR/CR rate improved from 80.2% in patients with 6 months of follow-up to 87.3% in patients with 12 or more months of follow-up. On the other hand, for a subset of 12 patients who had previously been treated with a CAR-T therapy, the ORR was 75% and 41.7% of patients (n = 5) achieved an sCR; it was noted that 4 of these 5 patients had an sCR that continued for more than 18 months following infusion. Among the whole group of 101 patients, 95% achieved minimal residual disease (MRD) negativity; among the 75 patients who achieved sCR/CR, 100% achieved MRD negativity. The rate of progression-free survival at 12 months of follow-up was 78.8% for all patients, 84.4% for patients who had not previously been treated with a CAR-T, and 89.5% in patients who achieved a CR or better.

The safety analysis for the trial included 103 patients. In this group, 96 patients (93.2%) experienced cases of cytokine release syndrome (CRS); only 1 patient (1%) experienced a case of CRS that was grade 3 or higher. The time to first onset for CRS ranged from 1 to 13 days (median, 6) and the duration of CRS ranged from 2 to 30 days (median, 5). The investigators noted that among patients with CRS cases, 65 (67.7%) were treated with glucocorticoids, 30 (31.3%) were treated with tocilizumab, and 72 (75%) were treated with glucocorticoids or tocilizumab. Meanwhile, there were 2 patients (1.9%) included in the safety analysis who experienced cases of immune effector cell-associated neurotoxicity syndrome (ICANS). There were no grade 3 or greater cases of ICANS reported. The time to first onset for ICANS ranged from 3 to 10 days (median, 6.5) and the duration of ICANS ranged from 1 to 2 days (median, 1.5). Li and colleagues also noted that the most common grade 3 or higher treatment-related adverse events in the trial were hematologic in nature.

With respect to the September 9, 2022, cutoff date for the data presented, 103 patients have received CT103A in the trial. Median follow-up for these patients ranged from 0.4 months to 27.2 months (median, 13.8). The ages of the treated patients ranged from 39 years to 70 years (median, 58). The group was composed of 55 men (53.4%) and 48 women (46.6%); in terms of ethnicity, 102 of the patients (99%) were Chinese. The number of previous lines of therapies received by the patients in the trial ranged from 3 to 23 (median 4) and the time since diagnosis ranged from 6.6 months to 193.2 months (median, 43.4). Twenty-four (23.3%) patients had an Eastern Cooperative Oncology Group (ECOG) score of 0 and 79 patients (76.7%) had an ECOG score of 1. Thirteen patients (12.6%) had extramedullary disease.

"MM is the second most prevalent hematological malignancy,” principal investigators Lugui Qi, MD, of the Chinese Academy of Medical Science Hematology Hospital, and Li said in a joint statement.3 “While current major drug therapies such as proteasome inhibitors, immunomodulators, and monoclonal antibodies have significantly improved MM treatments in the past 2 decades, it is still an incurable disease. The updated data from our ongoing clinical study of equecabtagene autoleucel presented at ASCO demonstrated that treatment with our BCMA-targeted CAR-T therapy was effective and well-tolerated for a longer period of time. In comparison to the clinical data released at the European Hematology Association 2022 Congress, we're excited that our updated study data show that with the number of subjects receiving equecabtagene autoleucel increasing from 79 to 103, and the median follow-up time from 9.0 months to 13.8 months, equecabtagene autoleucel's efficacy further improved: the sCR/CR rate increased from 68.4% to 74.3%. It is more worth mentioning that the sCR/CR rate reached 87.3% in the subjects naïve to BCMA-targeted CAR-T therapies and followed up for at least 12 months. These results are encouraging and entails an opportunity to advance equecabtagene autoleucel to earlier lines of treatment to benefit more MM patients."

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REFERENCES
1. Li C, Wang D, Song Y, et al. CT103A, a novel fully human BCMA-targeting CAR-T cells, in patients with relapsed/refractory multiple myeloma: Updated results of phase 1b/2 study (FUMANBA-1). Presented at: the American Society of Clinical Oncology (ASCO) 2023 Annual Meeting, held June 2-6, in Chicago, Illinois. Abstract #8025 Poster #17
2. 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. Accessed June 9, 2023. http://www.iasobio.com/info.php?id=209
3. Innovent and IASO Bio updated efficacy and safety clinical data of equecabtagene autoleucel (BCMA CAR-T cell therapy) for multiple myeloma at the 2023 ASCO annual meeting. News release. Innovent Biologics, Inc. June 5, 2023. Accessed June 9, 2023. https://www.prnewswire.com/news-releases/innovent-and-iaso-bio-updated-efficacy-and-safety-clinical-data-of-equecabtagene-autoleucel-bcma-car-t-cell-therapy-for-multiple-myeloma-at-the-2023-asco-annual-meeting-301842197.html
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