CAR-20/19-T Cells

P1, N=12, Recruiting, Medical College of Wisconsin | Not yet recruiting --> Recruiting

P1/2, N=100, Recruiting, Medical College of Wisconsin | Trial completion date: Jan 2025 --> Jun 2028 | Trial primary completion date: Jan 2025 --> Jun 2026

P1, N=24, Suspended, Medical College of Wisconsin | Recruiting --> Suspended

P1/2, N=100, Recruiting, Medical College of Wisconsin | Trial completion date: Dec 2025 --> Jan 2025 | Trial primary completion date: Dec 2025 --> Jan 2025

P1, N=12, Not yet recruiting, Medical College of Wisconsin | Trial completion date: Feb 2025 --> Jul 2027 | Initiation date: Apr 2024 --> Jul 2024 | Trial primary completion date: Nov 2024 --> Jul 2026

Cryopreservation of LV20.19 CAR T-cell therapy had no meaningful impact on ORR, DOR, toxicity profile, time to CRS, or in-vivo expansion. Although fresh products facilitate shorter time from apheresis to infusion, cryopreservation may allow for rapid advancement of products to multicenter trials and licensure.

12 pts (86%) had disease progression on covalent BTKi and venetoclax...In terms of safety, 100% (n=14) developed CRS and 93% (n=13) required tocilizumab...Six (66%) IEC-HS pts required anakinra for management... While LV20.19 CAR T cells were efficacious in CLL and RT it was limited by high rates of IEC-HS especially among CLL pts, a phenomena not commonly seen with other histologies. With two DLTs in the CLL cohort, the dose for future CLL pts was reduced to 1x10e6 cells/kg. Additional studies are needed to understand how CLL biology drives CAR IEC-HS.

P1, N=12, Not yet recruiting, Medical College of Wisconsin | Initiation date: Oct 2023 --> Feb 2024

Fludarabine/cyclophosphamide lymphodepletion was started during MF to facilitate fresh infusion in eligible pts...Both received only a single dose of intrathecal hydrocortisone (no systemic steroids) with resolution of neurotoxicity within 24 hours of administration... Bispecific LV20.19 CAR T-cells with adaptive MF process is feasible, safe, and efficacious for R/R MCL with ORR 100%, no Grade 3+ CRS and low rates of Grade 3+ ICANS (12%). Adaptive MF enriched the final product with higher percentages of T-SCM/T-CM CAR cells and allowed most pts to receive CAR-T cells within 8 days of apheresis. Dual targeting of CD20 and CD19 with CAR-T cells may improve outcomes in pts with relapsed, refractory MCL.

P1, N=24, Recruiting, Medical College of Wisconsin | Trial completion date: Feb 2024 --> Jun 2026 | Trial primary completion date: Oct 2023 --> Jun 2025

P1/2, N=100, Recruiting, Medical College of Wisconsin | N=65 --> 100 | Trial primary completion date: Dec 2023 --> Dec 2025

After safety run-in, we opened a 14-patient single stage Phase II MCL arm with flexible 8/12-day manufacturing (MF) and goal of fresh infusion with a target complete response (CR) rate of 50% to exceed the historical CR rate of Ibrutinib in R/R MCL of 20%...Eleven of 14 pts (79%) progressed on a Bruton's Tyrosine Kinase inhibitor (BTKi) and 5 (36%) of these pts also progressed on a non-covalent BTKi (pirtobrutinib) administered on a clinical trial...Bispecific LV20.19 CAR T-cells expanded with IL7/IL15 and manufactured onsite are safe and efficacious for R/R MCL with a day 90 ORR of 100%, and only one relapse to date with a median follow-up of nearly 2-years. Toxicity profile was encouraging with no Grade 3+ CRS and low rates of Grade 3+ ICANS. Dual targeting of CD19 and CD20 with CAR-T cells may improve outcomes in pts with R/R MCL.