Innovent Biologics, Inc., a world-class biopharmaceutical company that develops, manufactures and commercializes high-quality medicines for the treatment of cancer, metabolic, autoimmune and other major diseases, together with IASO Biotherapeutics (IASO Bio), today jointly announced that the results of initial clinical studies on treatment of relapsed or refractory multiple myeloma (R/R MM）in subjects using fully human BCMA-targeting CAR, an investigational chimeric antigen receptor (CAR) T-cell therapy co-developed by IASO Bio and Innovent was published in "Blood", a peer-reviewed medical journal specializing in hematology. The name of the article is "A phase 1 study of a novel fully human BCMA-targeting CAR (CT103A) in patients with relapsed/refractory multiple myeloma." The editors of "Blood" were so impressed by the unique persistence of IBI326 and the authors' exposition on the re-treatment prospects of the disease during the studies that they invited experts from University College London Cancer Institute to write a review entitled "BCMA CARs in multiple myeloma: room for more" (DOI 10.1182/blood.2021010833).
Background and results of IBI326 clinical studies:
Despite recent advances in multiple myeloma (MM) treatment strategies, particularly the emergence and clinical application of immunomodulatory drugs, proteasome inhibitors, and monoclonal antibodies that have improved the survival of MM, it remains an incurable plasma cell cancer, and relapse is almost inevitable in all patients. Results from previously published clinical trials showed that; 33% to 88% of patients with relapsed/ refractory MM (R/R MM) had objective antimyeloma responses after treatment with anti–B-cell maturation antigen (BCMA) chimeric antigen receptor (CAR) T cells 1-7. However, it remains a great challenge to achieve durable responses, and relapse or disease progression is observed in 28% to 88% of patients at a median follow-up time of 2 to 15 months 1-7.
The clinical study published in "Blood" was conducted in Department of Hematology, Tongji Medical College of HUST in China (ChiCTR1800018137). The results showed IBI326 has favorable safety profile with mild and controllable cytokine release syndrome (CRS). IBI326 shows excellent expansion and longer persistence during transfusion. In addition, subjects relapsed from a prior murine BCMA CAR-T treatment were also benefited from IBI326.
Efficacy:
IBI326 is highly active and induces quick and durable responses in subjects with R/R MM.
The ORR was 100% for all patients (18 of 18), with enhanced responses over time, and 72% (13 of 18) of the patients achieved complete response (CR) or stringent complete response (sCR). All patients evaluated for minimal residual disease (MRD, 17 of 17) in the bone marrow were MRD-negative at 10-4 nucleated cells by flow cytometry within 1 month; 9 of them were tested by next generation sequencing, and 4 patients achieved the best responses of MRD negativity by the level of 10-6 nucleated cells over time. The PFS and OS rate at 1 year were 58.3% and 75%, respectively. 1 year PFS rate was 79.1% for subjects without extramedullary myeloma (EMM). The patient with longest follow-up maintains sCR for over 2 years.
This study enrolled 4 patients who had previously been treated with a murine BCMA CAR for the 4 murine BCMA CAR-exposed patients. 3 achieved sCR, and 1 achieved a very good partial response (VGPR).
Safety: No Immune effector cell-associated neurotoxicity syndrome (ICANS) was observed in any of the dose groups. CRS was observed from 94% of the subjects, and there was a comparatively high rate of severe CRS (28% grade 3; 13% would have had grade 3 if the highest dose had been excluded). In dose expansion study, investigator recommended 1X106/kg CAR+ T cells as recommended Phase II dose.
CAR T-cell expansion: According to ddPCR-based CAR transgene quantification, the median time to reach peak concentration after infusion was 12 days (range, 7-26 days), a strong indication of rapid CAR expansion. No significant difference was observed among 3 dosing groups. For the 4 patients who had participated in prior murine BCMA CAR T-cell trials, low levels of expansions of previously infused murine CAR T cells were observed with short durations comp...
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