P1, N=18, Recruiting, The Children's Hospital of Zhejiang University School of Medicine

P1, N=30, Active, not recruiting, Memorial Sloan Kettering Cancer Center | Recruiting --> Active, not recruiting

P1, N=12, Not yet recruiting, Beijing Immunochina Medical Science & Technology Co., Ltd.

KYV-101 manufacturing yielded a CAR T-cell product with high viability and consistent composition and functionality, regardless of disease indication, pre-treatment, and heterogeneity of the incoming material. Cryopreservation of the apheresis and final drug product enabled widespread distribution. These results support the robustness of the manufacturing process for the fully human KYV-101 anti-CD19 CAR T-cell therapy drug product for patients across diverse autoimmune disease types.

P1/2, N=18, Not yet recruiting, Beijing GoBroad Hospital

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

P1/2, N=8, Not yet recruiting, Fondazione Policlinico Universitario Agostino Gemelli IRCCS

P1, N=0, Withdrawn, University Health Network, Toronto | N=40 --> 0 | Recruiting --> Withdrawn

P1, N=16, Active, not recruiting, Sana Biotechnology | Recruiting --> Active, not recruiting | N=57 --> 16 | Trial completion date: Dec 2027 --> Nov 2038 | Trial primary completion date: Dec 2026 --> Nov 2025

P1/2, N=18, Recruiting, Beijing GoBroad Hospital | Not yet recruiting --> Recruiting

P1, N=15, Not yet recruiting, Institute of Hematology & Blood Diseases Hospital, China

P1, N=32, Not yet recruiting, TG Therapeutics, Inc.

P2, N=27, Active, not recruiting, Fred Hutchinson Cancer Center | Recruiting --> Active, not recruiting

Further analysis of T cell phenotypes in the infused versus circulating CAR-T cells revealed the differentiation from early memory subtypes toward effector cells in vivo. The POC manufacturing and quality control settings herein could be applied to other CAR-T cell products and may benefit other academics, especially those in developing countries, making CAR-T cells more accessible.

P1/2, N=80, Recruiting, AstraZeneca | Trial completion date: Jun 2026 --> Jun 2028 | Trial primary completion date: Mar 2026 --> Dec 2026

No abstract available

P1/2, N=112, Recruiting, Shanghai AbelZeta Ltd. | Phase classification: P1b/2 --> P1/2 | N=72 --> 112 | Trial completion date: Mar 2027 --> Dec 2027 | Trial primary completion date: Mar 2027 --> Oct 2025

These findings underscore the significance of pre-treatment systemic inflammation (e.g. serum TNFa levels), product T cell phenotype, TMTV, CAR T-cell expansion, tumor IFN signaling and FLIPI as independent factors associated with clinical outcomes in patients with r/r FL treated with axi-cel. These results offer insights into mechanisms of resistance and toxicity, risk stratification, combination therapy and development of next-generation CAR-T therapy for patients with r/r FL.

Updated long-term follow-up from the ELARA trial continues to demonstrate robust durable responses >4 years post infusion, alongside a favorable safety profile. Correlative analyses suggest that most baseline high-risk disease characteristics (double-refractory disease, bulky disease, POD24, and high FLIPI) are not associated with inferior efficacy following tisagenlecleucel infusion in pts with r/r FL. Furthermore, high frequencies of MRD-negative status were achieved in a subset of evaluable pts.

"Introduction: Brexucabtagene autoleucel (brexu cel) is a CD19-targeted chimeric antigen receptor (CAR) T cell therapy approved for the treatment of adults with relapsed/refractory (R/R) acute lymphoblastic leukemia (ALL)...No differences were observed with respect to sex, TP53 mutation status, prior inotuzumab (ino) or blinatumomab (blina) exposure, disease burden prior to CAR, or development of any cytokine release syndrome (CRS) or any neurotoxicity with brexu cel... In a large real-world cohort of adults with R/R B-ALL infused with brexu cel, we identified practice variation regarding the use of consolidative HCT. Among brexu cel recipients who entered an MRD- CR, we identified ClonoSeq NGS MRD negativity as a novel predictive factor of favorable oncologic outcomes, even without a consolidative HCT. Similar results have been obtained in pediatric ALL patietns ftreated with 41BB-based tisagenleucleucel (Pulsipher et al., Blood Cancer Discovery 2022)."

Results from the ongoing ATALANTA-1 study show a manageable overall safety profile, with low rates of Grade ≥3 CRS and ICANS and high antitumor activity in all NHL subtypes studied. GLPG5101, a fresh, stem-like, early memory CD19 CAR T-cell therapy manufactured using a rapid decentralized platform, showed robust in vivo expansion and durable persistence. Treatment with GLPG5101 led to promising efficacy and safety across indications in heavily pretreated pts with R/R NHL.

Ten (77%) pts received blinatumomab as part of initial therapy...Among pts who completed the DLT period (n=11), 7 (64%) experienced transient grade (G) 1 cytokine release syndrome (CRS) that resolved with tocilizumab +/- corticosteroid... The use of CAR-T in older adults with B-ALL in CR1 appears safe with no observed ICANS or ≥G2 CRS. CAR T cells had a robust expansion in the blood and CSF despite the low antigen setting. We have observed preliminary durable remissions and pts maintained function and cognition on day 100 post CAR-T.

Eighty-four percent of responders to obe-cel for whom MRD by NGS could be analyzed achieved MRD <10–6 leukemic cells which was associated with more durable responses, and higher EFS and OS rates than those observed in pts with MRD ≥10–4 and between 10–4 and 10–6 leukemic cells. Pts who did not achieve MRD <10–6 had poorer outcomes.

P1, N=12, Not yet recruiting, Zhejiang University

P1/2, N=28, Not yet recruiting, Novartis Pharmaceuticals

P1/2, N=118, Recruiting, Gracell Biotechnologies (Shanghai) Co., Ltd. | Not yet recruiting --> Recruiting

P2, N=62, Active, not recruiting, Memorial Sloan Kettering Cancer Center | Trial completion date: Oct 2024 --> Oct 2025 | Trial primary completion date: Oct 2024 --> Oct 2025

Here, we describe a protocol to generate anti-CD19 CAR T cells and quantify human monocyte-derived IL-6 cocultured with CAR T cells and target tumor cells in vitro. We further describe a protocol to generate a humanized mouse model and evaluate CAR T cell-associated plasma IL-6 levels in vivo. For complete details on the use and execution of this protocol, please refer to Yoshikawa et al.1.

Elevated lactate levels correlated with longer CAR-T persistence and higher CD8+/CD4+ ratio. Peripheral blood lactate kinetics may reflect immune cells activation and be useful for bedside monitoring.

P1, N=12, Recruiting, Seattle Children's Hospital | Not yet recruiting --> Recruiting | Trial completion date: Jul 2041 --> Oct 2041 | Initiation date: Jul 2024 --> Oct 2024 | Trial primary completion date: Jul 2028 --> Oct 2028

Secondary malignancies seem more frequent after CAR-T therapies. More studies are needed to assess potential long-term toxicities of CAR-T cell therapies including the frequency of secondary myeloid malignancies.

P2, N=123, Not yet recruiting, Novartis Pharmaceuticals

P1/2, N=24, Active, not recruiting, St. Jude Children's Research Hospital | Trial completion date: Jul 2024 --> Jul 2025

P1/2, N=50, Recruiting, University of Washington | Trial completion date: Mar 2030 --> Mar 2031 | Trial primary completion date: Mar 2025 --> Mar 2026

P1/2, N=95, Active, not recruiting, Kite, A Gilead Company | Trial primary completion date: Mar 2026 --> Sep 2024

We report the case of long-term persisting rheumatoid arthritis (RA), treated with CD20-CD19 CAR-T when it became associated with diffuse large B cell lymphoma (DLBCL), resulting in a sustained drug-free remission of the preceding RA, as well as of the subsequent DLBCL that formed the indication of the CAR-T therapy using zamtocabtagene autoleucel, with a 1-year follow-up. According to our best knowledge, this is the first published clinical case report of long-term persisting RA treated with CAR-T cell therapy.

Importantly, although IL7/CD8 could promote T-cell proliferation, it did not sustain long-term autonomous expansion, which could ensure the safety of CD19 CAR-T cells expressing IL7/CD8 in clinical applications. Collectively, the IL7/CD8 construct represents a promising strategy for enhancing the therapeutic potential of CD19 CAR-T cell therapy.

P1/2, N=196, Active, not recruiting, The First Affiliated Hospital of Soochow University | N=98 --> 196

P2, N=86, Recruiting, Novartis Pharmaceuticals

We aimed to assess toxicity and efficacy of CD19-CAR T-cells in neurolymphomatosis...Findings suggest that CD19-CAR may sufficiently penetrate the blood-nerve barrier. Toxicity and outcomes were overall similar to CAR-T cell therapy in CNS lymphoma.

P3, N=108, Recruiting, Novartis Pharmaceuticals | Trial completion date: Feb 2029 --> Jan 2031

P2, N=36, Recruiting, City of Hope Medical Center | Trial completion date: Sep 2024 --> Dec 2024 | Trial primary completion date: Sep 2024 --> Dec 2024