P1/2, N=19, Active, not recruiting, Miltenyi Biomedicine GmbH | Trial completion date: Nov 2022 --> Sep 2024 | Trial primary completion date: Feb 2022 --> Sep 2024

P1/2, N=150, Recruiting, ImmPACT Bio | N=100 --> 150

P1, N=40, Not yet recruiting, Adicet Bio, Inc

P1, N=18, Recruiting, Ruijin Hospital

P1, N=78, Recruiting, Adicet Bio, Inc | Trial completion date: Mar 2024 --> Dec 2027 | Trial primary completion date: Mar 2023 --> Dec 2025

P1, N=100, Recruiting, Poseida Therapeutics, Inc. | Initiation date: Jan 2024 --> Apr 2024

P1/2, N=50, Recruiting, 2seventy bio | Trial primary completion date: Dec 2023 --> Aug 2024

P1, N=30, Recruiting, RenJi Hospital | Not yet recruiting --> Recruiting

P1, N=21, Not yet recruiting, Astellas Pharma Global Development, Inc. | Trial primary completion date: May 2031 --> Mar 2026

P1, N=42, Recruiting, Peking University Cancer Hospital & Institute

P1, N=114, Recruiting, Kite, A Gilead Company | Trial completion date: Jan 2027 --> Jul 2026 | Trial primary completion date: Jul 2025 --> Jul 2026

P1, N=36, Recruiting, Sumithira Vasu | Trial primary completion date: Dec 2023 --> Dec 2024

P1, N=33, Recruiting, The First Affiliated Hospital with Nanjing Medical University

P1, N=104, Recruiting, Janssen Research & Development, LLC | Trial completion date: Oct 2027 --> Oct 2028

P1/2, N=30, Recruiting, ImmPACT Bio | Not yet recruiting --> Recruiting

P1, N=18, Recruiting, Shanghai Longyao Biotechnology Inc., Ltd.

Although associated with moderate hematologic toxicity, CD20 CAR T-cells were well tolerated in SHIV-infected and control animals, supporting the feasibility of this therapy in people living with HIV with underlying B-cell malignancies. Our findings highlight the unique ability of CD20 CAR T cells to safely and reversibly unmask TFH cells within BCF sanctuaries, informing future combinatorial HIV cure strategies designed to augment antiviral efficacy.

P1/2, N=33, Recruiting, Han weidong | Trial primary completion date: Dec 2023 --> Dec 2024

P1, N=114, Recruiting, Kite, A Gilead Company | Trial completion date: Jan 2041 --> Jan 2027 | Trial primary completion date: Apr 2024 --> Jul 2025

P2, N=168, Recruiting, Miltenyi Biomedicine GmbH | Trial completion date: Dec 2024 --> Jul 2027 | Trial primary completion date: Dec 2023 --> Dec 2024

P1, N=30, Not yet recruiting, RenJi Hospital

P1, N=21, Not yet recruiting, Astellas Pharma Global Development, Inc.

P1, N=100, Recruiting, Poseida Therapeutics, Inc. | Not yet recruiting --> Recruiting | N=70 --> 100

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.

P1, N=104, Recruiting, Janssen Research & Development, LLC | Trial completion date: Apr 2027 --> Oct 2027

Preclinical evaluations of ATA3431 show B-cell tumor growth inhibition without any treatment-related toxicities and thereby support advancing ATA3431 for clinical evaluation.

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.

The primary objective of Phase 2 is to estimate the efficacy of IMPT-314 as measured by CR rate. Secondary endpoints include evaluation of pharmacokinetics and time to event outcomes.

We found that higher infused numbers of CD8 + CAR T cells with T N or T CM phenotypes, or low expression of certain exhaustion phenotype marker combinations, were associated with improved CAR-T expansion. We did not find any notable phenotypic signatures at baseline or in the IP that were predictive of prolonged CR, PFS, or toxicity, though the analysis was limited by a relatively small sample size. In FL, where a response to CAR-T therapy is almost universal, pre-manufacture and IP T cell phenotypes appear to have a lower importance for achieving an initial response than what has been reported in other settings with lower response rates (chronic lymphocytic leukemia, large B cell lymphoma).

P1/2, N=30, Not yet recruiting, ImmPACT Bio

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

P1, N=92, Recruiting, Janssen Research & Development, LLC | Not yet recruiting --> Recruiting | Phase classification: P1b --> P1 | N=52 --> 92 | Trial completion date: Nov 2026 --> May 2027 | Trial primary completion date: May 2026 --> Apr 2027

P1, N=92, Recruiting, Janssen Research & Development, LLC | N=52 --> 92 | Trial completion date: Oct 2027 --> Apr 2027

Preclinical evaluations of ATA3431 show B-cell tumor growth inhibition without any treatment-related toxicities and thereby support advancing ATA3431 for clinical evaluation. Curran KJ, Sauter CS, Kernan CS, et al. Durable remission following "off-the-shelf" chimeric antigen receptor (CAR) T-cells in patients with relapse/refractory (R/R) B-cell malignancies.

Before lymphocyte collection, chemotherapy regimen without fludarabine/ Bendamustine is first used to reduce peripheral blood tumor load if peripheral blood tumor cells are higher than 10%...12 of them were injected with mouse CD19CAR-T, 2 with human CD20CART, and 2 with human CD19CART... Even in the presence of TP53 gene abnormalities, resistance to BTK/BCL2 inhibitors, and unsuccessful previous chemotherapy regiments, A single CAR T cell therapy can result in CR in more than half of RT patients. Nonetheless, the prognosis remains bleak for patients presenting with large tumor masses and central nervous system involvement, despite having received chemotherapy aimed at reducing tumor size. The outlook is particularly dismal for those patients who fail to respond to CAR-T cell therapy.

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.

ADI-001 Cmax and D28 persistent exposure were comparable to, or exceeded, those demonstrated by alternative allogeneic CAR T therapies and approved autologous CD19 CAR T therapies. Favorable clinical responses were also associated with higher mean and median peak of ADI-001 cells.

TALEN® gene editing technology is used to inactivate the TRAC and CD52 genes to minimize graft-versus-host disease (GvHD) and allow for the use of alemtuzumab (CLLS52, an anti-CD52 monoclonal antibody) in the lymphodepletion (LD) regimen, respectively...After LD with FCA (fludarabine 30 mg/m2 × 3d, cyclophosphamide 0.5g/m2 × 3d, CLLS52 12 mg on D1, 24 mg on D2, D3), a single infusion of UCART20x22 is administered at a flat dose level ([DL1] 50 x 106 cells; [DL2] 150 x 106 cells; and [DL3] 450 x 106 cells)...Pt 3 is an 18yo female with R/R DLBCL transformed from marginal zone lymphoma who previously received chemoimmunotherapy, venetoclax, ibrutinib, BR, CAR19, obinutuzumab, glofitamab, tafasitamab, lenalidomide, and an experimental epigenetic modifier...Pt 1 had G1 CRS and received tocilizumab (toci) x3 and dexamethasone (dex) x1... As of 01 July 2023, 3 pts were enrolled and treated at DL1. Pt 1 is a 76yo female with double-expressor diffuse large B-cell lymphoma (DLBCL) relapsed after R-CHOP, radiation therapy, and polatuzumab vedotin with bendamustine/rituximab (BR) and was considered ineligible for CAR19 due to recent high dose bendamustine. Pt 2 is a 65yo female with R/R triple-hit lymphoma transformed from follicular lymphoma who was previously treated with radiation therapy, BR, dose-adjusted R-EPOCH, and two separate CAR19 treatments.

This pt recovered after receiving corticosteroids and tocilizumab. Longer term follow-up demonstrated that C-CAR066 can produce a deep and durable response with a favorable safety profile in pts with r/r LBCL who failed prior CD19 CAR-T therapy.

Following lymphodepletion (cyclophosphamide 300 mg/m2/day and fludarabine 30 mg/m2/day for 3 days), MB-106 is administered to patients with indolent B-cell NHL at one of two dose levels (DL): DL1, 3.3×106; and DL2, 1.0×107 cells/kg. Treatment with MB-106, a third generation CD20 targeting CAR-T, resulted in responses, including CRs, and CAR-T persistence in patients with R/R indolent NHL and was associated with favorable safety profile with no occurrence of Grade 3 or Grade 4 cytokine release syndrome and no ICANS of any grade. CRs have been observed in patients previously treated with CD19-targeted CAR-T in both this multicenter trial and the original single institution trial. Dosing is ongoing in the final dosing level (1.0×107 cells/kg) to establish the recommended Phase 2 dose for a planned pivotal trial in WM.

P1/2, N=100, Recruiting, ImmPACT Bio | N=50 --> 100

P1, N=24, Recruiting, Jonsson Comprehensive Cancer Center | Trial completion date: Aug 2024 --> Aug 2025 | Trial primary completion date: Aug 2023 --> Aug 2024