Yescarta (axicabtagene ciloleucel)

No abstract available

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.

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

Here, we report three cases of severe ICAHT after axicabtagene-ciloleucel (axi-cel) for diffuse large B-cell lymphoma showing an expansion of large granular lymphocyte in the bone marrow with a CD3/CD57-positive non-CAR-T immunophenotype. We show that it is possible to treat them with low-dose steroids, obtaining a striking resolution of cytopenias with no deleterious impact on the underlying malignancy.

P4, N=20, Recruiting, Zhengzhou University | Not yet recruiting --> Recruiting

We conclude that the addition of nivolumab based on CAR-T cell expansion in patients with SD/PD-LBCL is safe and yields promising early response rates.

P2, N=62, Active, not recruiting, The Lymphoma Academic Research Organisation | Trial completion date: Jun 2024 --> Jun 2026

P2, N=30, Active, not recruiting, Kite, A Gilead Company | Trial primary completion date: Mar 2026 --> Sep 2024

P4, N=20, Not yet recruiting, Zhengzhou University

We analyzed serial peripheral blood samples ranging from day of apheresis (day -28/baseline) to 28 days after CAR-T infusion from 50 patients with LBCL treated with axicabtagene ciloleucel (axi-cel) by integrating single cell RNA and TCR sequencing (scRNA-seq/scTCR-seq), flow cytometry, and mass cytometry (CyTOF) to characterize features associated with response to CAR-T...Our results suggest that patients' immunologic state at baseline affects likelihood of response to CAR-T through both modulation of the T cell apheresis product composition and promoting a more favorable circulating immune compartment prior to therapy. These baseline immunologic features, measured readily in the clinical setting prior to CAR-T, can be applied to predict response to therapy.

Our study suggests that r/r DLBCL patients with both DE status and TP53 alterations treated with CAR-T therapy are more likely to have a poorer clinical prognosis. However, CAR-T therapy has the potential to improve the prognosis of patients with only TP53 alterations or DE status to be similar to that of patients without these abnormalities.

P=N/A, N=36, Not yet recruiting, M.D. Anderson Cancer Center

Based on these findings, prophylactic tocilizumab is not recommended to prevent CAR T-cell-related adverse events, and beneficial effects of prophylactic levetiracetam remain uncertain in patients with R/R LBCL.

P2, N=40, Recruiting, M.D. Anderson Cancer Center | Trial primary completion date: Sep 2024 --> Aug 2026

P2, N=27, Recruiting, H. Lee Moffitt Cancer Center and Research Institute | Trial completion date: Nov 2026 --> Dec 2025

P2, N=27, Recruiting, H. Lee Moffitt Cancer Center and Research Institute | Trial completion date: Oct 2027 --> Jul 2026 | Trial primary completion date: Oct 2027 --> Jul 2025

P1, N=20, Recruiting, AIDS Malignancy Consortium | Not yet recruiting --> Recruiting

Patients with a CRS-PSS score > 2 had significantly higher risk to develop grade ≥ 3 ICANS. Both scores were externally validated in international cohorts of patients treated with tisa-cel or axi-cel.

P=N/A, N=35, Not yet recruiting, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology; Fosun Kite Biotechnology Co., Ltd

P2, N=32, Recruiting, The First Affiliated Hospital of Soochow University; Fosun Kite Biotechnology Co., Ltd. | Not yet recruiting --> Recruiting

P4, N=200, Recruiting, Union Hospital of Tongji Medical College of Huazhong University of Science and Technology; Fosun Kite Biotechnology Co., Ltd | Not yet recruiting --> Recruiting

P2, N=36, Recruiting, Jonsson Comprehensive Cancer Center | Trial completion date: Jun 2025 --> Jun 2026 | Trial primary completion date: Jun 2024 --> Jun 2025

P1, N=15, Terminated, Kite, A Gilead Company | Phase classification: P1/2 --> P1

P1, N=18, Active, not recruiting, Dana-Farber Cancer Institute | Trial primary completion date: Jun 2024 --> Dec 2024

Pre-treatment malnutrition and cachexia was significantly associated with adverse CAR T patient outcomes, including mGPS cachexia status independently associated with inferior overall survival. Further research in this novel space is essential to confirm the extent and impact of nutritional issues, to assist with implementing dietetic pathways, and to identify potential interventions with a view to optimising outcomes.

Our results highlight the rarity of second tumors and provide a framework for defining clonal relationships and viral vector monitoring. (Funded by the National Cancer Institute and others.).

Scenarios one and two resulted in ICERs of $105,353 and $102,695, respectively. This study finds that axi-cel is cost-effective compared to mosun at the commonly cited $150,000/QALY US willingness-to-pay threshold, with robust results across a range of sensitivity analyses accounting for parameter uncertainty.

P2, N=27, Recruiting, H. Lee Moffitt Cancer Center and Research Institute | Trial completion date: May 2026 --> Nov 2026 | Trial primary completion date: Jun 2024 --> Oct 2024

P1/2, N=307, Completed, Kite, A Gilead Company | Trial primary completion date: Sep 2020 --> Jul 2023

P2, N=22, Completed, M.D. Anderson Cancer Center | Active, not recruiting --> Completed | Trial completion date: Jan 2025 --> May 2024 | Trial primary completion date: Jan 2025 --> May 2024

Using independent datasets, we validate that CD8-fit T cells (1) are present premanufacture and are associated with clinical responses in individuals treated with axicabtagene ciloleucel, (2) longitudinally persist in individuals after treatment with CAR T cells and (3) are tumor migrating cytolytic cells capable of intratumoral expansion in solid tumors. Our results demonstrate the power of multimodal integration of single-cell functional assessments for the discovery and application of CD8-fit T cells as a T cell subset with optimal fitness in cell therapy.

P2, N=40, Recruiting, M.D. Anderson Cancer Center | Not yet recruiting --> Recruiting

Bendamustine has been retrospectively shown to be an effective and safe lymphodepletion regimen prior to the anti-CD19 chimeric antigen receptor T cell (CART) products tisagenlecleucel and axicabtagene ciloleucel, as well as the anti-BCMA CART products idecabtagene vicleucel and ciltacabtagene autoleucel. Neutropenia ≥ grade 3 was observed in 29.0% of patients; thrombocytopenia ≥ grade 3 occurred in 9.7%. In conclusion, bendamustine lymphodepletion before liso-cel appears to be a strategy that can drive tumor responses while ensuring a mild toxicity profile.

P2, N=15, Active, not recruiting, Marcela V. Maus, M.D.,Ph.D. | Completed --> Active, not recruiting | Trial completion date: Oct 2023 --> Oct 2025 | Trial primary completion date: Oct 2022 --> Oct 2024

present data from pretreatment tumor biopsies taken on the ZUMA-7 trial. Their results identify tumor microenvironment (TME) contexts and level of CD19 expression as prognostic indicators for responses to axicabtagene ciloleucel (axi-cel).

Among possible determinants of CD4+ T cell recovery, we recognized infusion of a 4-1BB product (tisagenlecleucel, TSA) in comparison with a CD28 (axicabtagene/brexucabtagene, AXI/BRX) (hazard ratio [HR] [95% CI]: 5.79 [1.16-24.12] p = 0.016). We conclude that a faster CAR- CD4+ T cell recovery is associated with TSA as compared to AXI/BRX. Month-1 CAR- CD4+ T cell subset recovery could represent a "red flag" for CAR-T cell therapy failure in DLBCL patients.

P2, N=700, Enrolling by invitation, Kite, A Gilead Company | Trial completion date: Mar 2041 --> Dec 2040 | Trial primary completion date: Mar 2041 --> Dec 2040

P2, N=35, Active, not recruiting, Kite, A Gilead Company | Recruiting --> Active, not recruiting

P3, N=230, Recruiting, Kite, A Gilead Company | Trial completion date: Jan 2031 --> Oct 2030 | Trial primary completion date: Jan 2031 --> Oct 2030

P2, N=396, Recruiting, SWOG Cancer Research Network | Trial primary completion date: Dec 2024 --> Dec 2025

P=N/A, N=144, Active, not recruiting, Masonic Cancer Center, University of Minnesota | Recruiting --> Active, not recruiting | N=240 --> 144 | Trial primary completion date: Jun 2028 --> Feb 2024

P3, N=359, Active, not recruiting, Kite, A Gilead Company | Trial completion date: Jan 2035 --> Oct 2024