P1/2, N=28, Recruiting, Novartis Pharmaceuticals | Not yet recruiting --> Recruiting

P1, N=15, Not yet recruiting, City of Hope Medical Center

P1, N=10, Recruiting, Institute of Hematology and Blood Transfusion, Czech Republic | Trial completion date: Jun 2025 --> Dec 2025 | Trial primary completion date: Dec 2024 --> Jun 2025

Multi-target approaches, e.g. the bispecific BCMA×CD19 CAR-T product GC012F, are advancing through clinical development with encouraging safety and efficacy data. However, randomized controlled trials will be necessary to confirm the role and positioning of CD19-directed CAR-T cells within the current MM treatment landscape.

P1, N=12, Recruiting, Shanghai Cell Therapy Group Co.,Ltd

P1, N=90, Recruiting, Nkarta, Inc.

Here, we profiled IR in 263 patients with relapsed/refractory large B-cell lymphoma receiving CAR-T therapy (axicabtagene ciloleucel 44.9%, lisocabtagene maraleucel 30.4%, tisagenlecleucel 24.7%). IR differences exist by product, with fastest CD4+ T cell recovery seen for tisagenlecleucel, driven primarily by more rapid recovery of the CD4+CCR7-45RA- effector memory subset. Natural killer cell, but not CD4+ T cell, recovery is significantly associated with favorable progression-free (HR: 0.647; 95% CI: 0.476-0.880) and overall survival (HR: 0.637; 95% CI: 0.441-0.920) and inversely correlated with inflammatory markers measured at time of infusion.

P1, N=54, Recruiting, Roswell Park Cancer Institute | N=36 --> 54

In vivo, shRNA-mediated knockdown of CUL5 enhances CD19 CAR T treatment outcomes in tumor-bearing mice. Our findings thus imply that targeting CUL5 in the ubiquitin system may enhance CAR T cell effector functions to enhance immunotherapy efficacy.

P2, N=123, Recruiting, Novartis Pharmaceuticals | Not yet recruiting --> Recruiting

P1/2, N=18, Recruiting, Beijing GoBroad Hospital | Not yet recruiting --> Recruiting | Trial completion date: Dec 2025 --> Dec 2026

P2, N=20, Recruiting, University Medical Center Groningen | Trial completion date: May 2025 --> May 2026 | Trial primary completion date: May 2024 --> Apr 2025

Therapeutically relevant doses of CD19/CD22 CAR-T cells can be successfully manufactured from whole blood. On average, 80 mL of whole blood yields enough CAR-T cells to create a single dose for a pediatric patient (50 kg) at a dosage of 1 × 106 CAR-T cells/kg. For larger patients, scaling up is straightforward by collecting a larger blood volume. This method also demonstrates a cost-effective approach to T cell activation and expansion which, alongside a more straightforward collection of whole blood, makes it more widely accessible especially for middle- and low-income countries. By reducing costs and labor, this strategy has the potential to significantly expand global access to CAR-T cell therapy.

P1/2, N=81, Recruiting, University of Sao Paulo | Not yet recruiting --> Recruiting

P1, N=106, Recruiting, Umoja Biopharma | Not yet recruiting --> Recruiting

Incorporation of blinatumomab and/or inotuzumab in CR1 may mitigate the negative prognostic significance of MRD, however it is unclear if intensity of standard post-remission therapy can be safely reduced without compromising outcomes...We designed a phase I clinical trial to determine safety and tolerability of UCD19 CAR-T cell therapy for adults with B-ALL in MRD+ CR1 who are at high risk for relapse.Methods : Eligible patients include adults (≥18yo) with B-ALL in CR1 after induction therapy, with MRD positivity by either flow cytometry or NGS (Clonoseq)...Longer follow-up is needed to determine if remissions remain durable, and to determine the relationship between functional persistence (as measured by B-cell aplasia) and remission durability. Enrollment is ongoing at DL2.

P=N/A, N=60, Not yet recruiting, National Research Center for Hematology, Russia

P1, N=40, Recruiting, Atara Biotherapeutics | Initiation date: Jan 2024 --> Sep 2024

Consistently, in vivo experiments demonstrated that the CD4+CD25+ Treg population dampened the antitumor activity of CD8+CAR-T cells, while depletion of Tregs from CD4+CAR-T cells enhanced the tumoricidal effect. These findings emphasize the potential role of CAR Treg cells in therapeutic resistance, suggesting that the depletion of Tregs in the anti-CD19 CAR-T population may serve as a strategy to augment the anticancer effect of CD8+CAR-T cells.

P2, N=20, Not yet recruiting, Ruijin Hospital

The present report describes the cases of 2 patients with relapsed DLBCL treated with CAR T-cell therapy, in which the severe CRS associated with CAR T-cell therapy was attenuated without compromising antitumor efficacy after receiving emapalumab. Further prospective clinical trials are warranted to determine the role of emapalumab in CAR T-cell therapy.

P1, N=71, Active, not recruiting, City of Hope Medical Center | Trial completion date: Sep 2024 --> Sep 2025 | Trial primary completion date: Sep 2024 --> Sep 2025

P1, N=36, Recruiting, Zhejiang University

P1, N=20, Not yet recruiting, Takeda | Initiation date: Nov 2024 --> May 2025

P2, N=168, Active, not recruiting, Miltenyi Biomedicine GmbH | Trial completion date: Jul 2027 --> Jul 2029

P1/2, N=60, Recruiting, National Research Center for Hematology, Russia | Not yet recruiting --> Recruiting

P1/2, N=30, Recruiting, Chinese PLA General Hospital | Trial completion date: Jul 2027 --> Feb 2028 | Initiation date: Jul 2024 --> Feb 2025 | Trial primary completion date: Jul 2026 --> Feb 2027

P1, N=36, Recruiting, Zhejiang University

P1, N=5, Not yet recruiting, National University of Malaysia

P1, N=48, Not yet recruiting, Miltenyi Biomedicine GmbH

P1, N=42, Recruiting, Synthekine | Initiation date: Sep 2024 --> Dec 2024

The development of a fatal, clonal, autonomously proliferating CD4-CD8- chimeric antigen receptor (CAR)+ peripheral T-cell lymphoma (PTCL) occurred 1 month after a patient received treatment with tisagenlecleucel for relapsed primary central nervous system lymphoma. Somatic DNMT3A and TET2 mutations in CD34+ stem cells and their progeny were detected in the PTCL, in the apheresis specimen that was obtained for CAR T-cell production, and in the autotransplant. The PTCL harbored an additional somatic TET2 mutation, which was already detectable in the CAR T-cell apheresis product and the final CAR T-cell product at very low frequencies, providing evidence that clonal hematopoiesis had contributed to lymphomagenesis.

P1/2, N=15, Not yet recruiting, Novartis Pharmaceuticals

P1/2, N=60, Not yet recruiting, National Research Center for Hematology, Russia

P1, N=18, Not yet recruiting, GenomeFrontier Therapeutics TW Co., Ltd.

P=N/A, N=60, Not yet recruiting, Verismo Therapeutics

Our findings indicate that renal dysfunction is a common toxicity of CAR T cell therapy with meaningful prognostic impact. Notably, the link between systemic inflammation and renal dysfunction, suggests that readily available biomarkers may inform on renal injury risk after CAR T cell therapy.

P2, N=20, Recruiting, National University of Malaysia

P1, N=12, Recruiting, Nanjing Bioheng Biotech Co., Ltd. | Not yet recruiting --> Recruiting

We optimized different dual-targeting approaches, including co-transduction of two lentiviral vectors, bicistronic, tandem, loop and pool strategies, based on our academic anti-CD19 (ARI0001) and anti-BCMA (ARI0002h) CAR-T cells. ARI0003 CAR-T cells were effectively manufactured under Good Manufacturing Practice conditions, with reduced risk of genotoxicity compared to other dual-targeting approaches. A first-in-human phase I clinical trial (CARTD-BG-01, NCT06097455) has been initiated to evaluate the safety and efficacy of ARI0003 in NHL.

P=N/A, N=15, Enrolling by invitation, Bioray Laboratories | Recruiting --> Enrolling by invitation

P=N/A, N=150, Recruiting, Miltenyi Biomedicine GmbH | Not yet recruiting --> Recruiting