ATA2271

We use a nonablative dose of tumor-targeted radiation prior to systemic administration of mesothelin-targeted CAR T cells to assess infiltration, proliferation, antitumor efficacy, and functional persistence of CAR T cells at primary and distant sites of tumor...Our results strongly suggest that the use of tumor-targeted radiation prior to systemic administration of CAR T cells may substantially improve CAR T-cell therapy efficacy for solid tumors. Building on our observations, we describe a translational strategy of "sandwich" cell therapy for solid tumors that combines sequential metastatic site-targeted radiation and CAR T cells-a regional solution to overcome barriers to systemic delivery of CAR T cells.

P1, N=30, Recruiting, Memorial Sloan Kettering Cancer Center | Active, not recruiting --> Recruiting | Trial completion date: Sep 2023 --> Sep 2024 | Trial primary completion date: Sep 2023 --> Sep 2024

P1, N=7, Active, not recruiting, Memorial Sloan Kettering Cancer Center | Recruiting --> Active, not recruiting | N=30 --> 7

Clinical safety and systemic persistence of M28z1XXPD1DNR CAR T cells was investigated in 4 pleural mesothelioma patients (NCT04577326)...Legal entity responsible for the study Memorial Sloan Kettering Cancer Center. Funding ATARA Biotherapeutics.

Stable disease was sustained for {greater than or equal to}6 months in 8 patients; 2 exhibited complete metabolic response on PET scan. Combination immunotherapy with CAR T cells and PD-1 blockade agents should be further evaluated in patients with solid tumors.

P1, N=30, Recruiting, Memorial Sloan Kettering Cancer Center | Trial completion date: Sep 2022 --> Sep 2023 | Trial primary completion date: Sep 2022 --> Sep 2023

Median number of prior therapies was 1, including 8 pts w/ previous allogeneic hematopoietic cell transplant (alloHCT) and 5 w/ prior chimeric antigen receptor T-cell therapy (CAR-T)...One pt w/ grade 2 CRS received tocilizumab for hypotension suboptimally responsive to fluid boluses (FB) w/ IL-6 level = 25754 pg/mL...Peak APR levels correlated w/ CRS severity. Authors noted concordance of CRS grading between CTCAE and ASTCT, suggesting the feasibility of a single, BITE-specific grading system.

Methods We analyzed 2 different populations of adult CAR T cells pts treated at our institution: 1) B-cell acute lymphoblastic leukemia (B-ALL) pts treated with CD1928z CAR T cells from 2010 to 2016 (NCT01044069), and 2) aggressive diffuse large B-cell lymphoma (DLBCL) pts treated with axicabtagene ciloleucel (axi-cel) or tisagenlecleucel (tisa-cel) after FDA approval starting from 2018...Moreover, both high EASIX and mEASIX scores on day +1 and day +3 are associated with occurrence of grade ≥3 CRS and grade ≥3 ICANS, respectively. We conclude that EASIX and mEASIX, as markers of endothelial damage and inflammation, could be useful as early predictors in guiding treatment decisions before the onset of severe symptoms.