anitocabtagene autoleucel (CART-ddBCMA)

P1, N=30, Not yet recruiting, Arcellx, Inc.

P3, N=450, Recruiting, Kite, A Gilead Company | Not yet recruiting --> Recruiting

P3, N=450, Not yet recruiting, Kite, A Gilead Company

Briefly, pts with RRMM who have received ≥3 prior lines of therapy were enrolled & received a single infusion of CART-ddBCMA following lymphodepletion chemotherapy (fludarabine: 30 mg/m2/d & cyclophosphamide: 300 mg/m2/d daily for 3 days). Adverse events with CART-ddBCMA, including CRS & ICANS, were manageable & no off-tumor tissue-targeted toxicity, delayed neurotoxicity, or Parkinsonian-like events were observed in the entire cohort at the time of data-cut. Ongoing efficacy results are encouraging, with 100% ORR, including 35 (92%) response of VGPR or better & 29 (76%) with CR/sCR. More importantly, clinical responses were durable with an overall estimated 18-mo PFS rate of 67% with comparable clinical responses seen in 'high-risk' patients known to have poor prognosis.

P1, N=65, Recruiting, Arcellx, Inc. | Trial primary completion date: Aug 2022 --> Aug 2024

Lymphodepletion is administered (fludarabine (30 mg/m2/day) and cyclophosphamide (300 mg/m2/day)) daily on days -5 to -3, then CART-ddBCMA is given as a single infusion on day 0. Adverse events including CRS and ICANS were manageable and no off-tumor tissue-targeted toxicity, delayed neurotoxicity, or Parkinsonian-like events were observed in the entire cohort. Ongoing efficacy results are encouraging, with 100% ORR, including 29 (94%) demonstrating deep clinical responses of ≥VGPR and 22 (71%) with CR/sCR. At the time of the meeting, updated data will be presented.

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. Conclusions CART-ddBCMA has demonstrated clinical activity, including 100% ORR & durable responses.

Pts receive fludarabine and cyclophosphamide (30/300 mg/m2/day) days -5 to -3 and CART-ddBCMA infusion on day 0. CART-ddBCMA administration, to date, has demonstrated clinical activity, including 100% ORR with rates of CR/sCR and ≥VGPR of 67% and 88%, respectively. Durable responses beyond 18 months have been observed, including in pts with EMD.

Subjects undergo lymphodepletion with fludarabine (30 mg/m 2 ) and cyclophosphamide (300 mg/m 2 ) daily for 3 days, then receive CART-ddBCMA as a single infusion...Thirteen subjects (81%) received at least 1 dose of tocilizumab and 5 (31%) received steroids (dexamethasone). 2 subjects (13%) experienced grade 3 ICANS and were given anakinra plus dexamethasone... Ongoing efficacy results are encouraging, with 100% ORR, including 12 (75%) demonstrating deep clinical responses of ≥VGPR and 9 (56%) with CR/sCR. Of those evaluable (n=12), all subjects, but one, have achieved MRD-negative bone marrow responses at 1 month, and demonstration of deeper response has occurred at later timepoints. Dose escalation was completed, and expansion is continuing at DL1.

Subjects undergo lymphodepletion with fludarabine (30 mg/m2) and cyclophosphamide (300 mg/m2) daily for 3 days, then receive CART-ddBCMA as a single infusion...These adverse effects resolved quickly after intervention; 3 subjects received tocilizumab and 2 received steroids (dexamethasone)...Subjects continue to be enrolled and treated. Additional subjects, and longer follow-up will establish whether treatment with CART-ddBCMA results in durable CAR+ T responses.