Chimeric Antigen Receptor (CAR) T cell therapies targeting B-cell maturation antigen (BCMA) have demonstrated benefit in patients (pts) with relapsed/refractory Multiple Myeloma (RRMM). CART-ddBCMA is an autologous anti-BCMA CAR T cell therapy that utilizes a novel, synthetic binding domain, called a D-Domain, instead of a typical scFv binder. The objective of this first-in-human trial is to assess the safety & efficacy of CART-ddBCMA.
This is a phase I, multi-center, open label, dose escalation trial for pts with RRMM who have received ≥3 regimens or are triple refractory. Lymphodepletion is given days -5 to -3 followed by CART-ddBCMA infusion on day 0. Dose escalation was performed at 100 (DL1) & 300 (DL2) x 106 (± 20%) CAR+T cells, followed by expansion of DL1. The primary outcome measure is incidence of adverse events (AEs), including dose-limiting toxicities. Additional outcome measures are ORR, CR rate, DoR, MRD (clonoSEQ), PFS & OS.
As of Jan 25, 2022, 25 pts received CART-ddBCMA, with median age 66 (range: 44-76), after a median of 5 prior lines of therapy (3-16), including 10 (40%) with extramedullary disease (EMD). Median follow-up was 296 d (58-716 d). Overall, 25 pts (19 DL1; 6 DL2) were evaluable for safety & 24 (18 DL1; 6 DL2) for efficacy analysis. All pts experienced CRS, but only 1 pt (in DL2) had grade (G) 3 CRS. All other CRS cases were G≤2, with no cases of G≥3 CRS in DL1. Four pts experienced ICANS (2, G≤2; 2, G3), with 1 G3 case in each of DL1 (5%) & DL2 (17%). All cases resolved without sequalae with standard management. The ORR was 100%, sCR/CR rate 67% & ≥VGPR rate 88%. Conversion to CR/sCR was observed with longer follow-up, as late as month 9 in this trial, & 5 pts with PR /VGPR in the DL1 have <9 months follow-up, with 4 (of 4 evaluable) negative at ≥10-5 for MRD. Overall, 17/20 (85%) evaluable pts have achieved best MRD response of ≥10-5. Of the first 6 pts dosed in DL1, 4 (67%) continue in ongoing sCR beyond 18 months, including 3 with EMD. Median duration of response, PFS & OS were not evaluable at the time of data-cut because 19 of 24 evaluable pts (79%) remain in ongoing response.
CART-ddBCMA has demonstrated clinical activity, including 100% ORR & durable responses.
Clinical trial identification
Legal entity responsible for the study
M. Frigault: Financial Interests, Personal, Other, Consultant: Celgene, Arcellx; Financial Interests, Personal, Research Grant: Novartis, Kite. J. Rosenblatt: Financial Interests, Personal, Other, Consultant: Attivare, Wolters Kluwer Health; Financial Interests, Personal, Research Grant: BMS. N. Raje: Financial Interests, Personal, Other, Consultant: Celgene. C. Cornwell: Financial Interests, Personal, Full or part-time Employment: Arcellx. K. Banerjee: Financial Interests, Personal, Full or part-time Employment: Arcellx. A. Rotte: Financial Interests, Personal, Full or part-time Employment: Arcellx. C. Heery: Financial Interests, Personal, Full or part-time Employment: Arcellx. D. Avigan: Financial Interests, Personal, Advisory Board: Celgene, Juno, Partner Tx, Karyopharm, BMS, Aviv MedTech, Takeda, Legend, Chugai; Financial Interests, Personal, Research Grant: Pharmacyclics, Kite; Financial Interests, Personal, Other, Consultant: Parexel. A. Jakubowiak: Financial Interests, Personal, Advisory Board: BMS, Celgene, Abbvie, Gracell, GSK, Janssen, Karyopharm, Amgen, Sanofi. M. Bishop: Financial Interests, Personal, Research Grant: Kite; Financial Interests, Personal, Invited Speaker: Incyte, BMS; Financial Interests, Personal, Member of the Board of Directors: Autolus, Novartis, CRISPR. All other authors have declared no conflicts of interest.