ALLO-715

Other Constructs of Interest Orva-cel (orvacabtagene autoleucel) is an anti-BCMA CAR T product with a construct containing a fully human scFv, an optimized spacer, a 4-1BB co-stimulatory domain, and a CD3z activation domain...Bb21217 has an identical construct to ide-cel except for coculturing with the phosphoinositide 3 kinase inhibitor (PI3K) bb007 during ex vivo culture to enrich for T cells displaying a memory-like phenotype...The ORR was 94%.17 P-BCMA-101 is a novel construct using an anti-BCMA Centyrin™ fused to a 4-1BB costimulatory domain and CD3z signaling domain...Both ide-cel and cilta-cel are being evaluated in various patient populations, including early-relapse and newly diagnosed high-risk patients...The first results of an allogeneic BCMA-directed CAR-T was with ALLO-715. The initial results from the UNIVERSAL phase 1 study in RRMM are encouraging, with responses reported and more attenuated toxicity.26 Others, including CTX120, BCMAUCART, UCART CS1, and PBCAR269A, are in development and in early-phase studies...Despite these impressive results, however, patients with MM continue to relapse. Moving these therapies earlier in the course of the disease, continued refinement of next-generation products, and rational combination strategies that may defer or prevent relapse should continue to improve on these results with the goal of finally reaching that elusive cure.

These include: FCA (fludarabine (F) 90 mg/m2, cyclophosphamide (C) 900 mg/m2, and ALLO-647 (A) 39 mg divided over 3 days), FCA+ (same F and C but ALLO-647 (A+) dose of 90 mg divided over 3 days); as well as CA (same C and A divided over 3 days, but no F given)...Three episodes were Grade 1 and 1 was Grade 2 (Lee Grading); all resolved without tocilizumab or corticosteroids...Updated safety, efficacy, PK/PD data will be presented. Clinical trial information: NCT04093596.