Background: Solid tumors are notoriously heterogenous with highly variable antigen expression and an immunosuppressive microenvironment. HLA loss of heterozygosity (LOH) has also been identified in up to 40% of solid tumors, allowing tumor cells to evade T cell attack. To overcome these issues and a lack of potent endogenous antitumor T cells in cancer patients, TScan has developed T-Plex, a multiplexed cell therapy comprising two to three different TCR-Ts, chosen from a collection of TCR-Ts called the ImmunoBank. Product and study design details were presented at ASCO 2023 (Abstract #2554). Methods: A screening protocol (NCT05812027) pre-identifies patients with solid tumors any time during clinical care, enabling rapid enrollment into the treatment protocol (NCT05973487) upon disease progression. TCR-Ts currently in the master protocol target PRAME on HLA-A*02:01; HPV16 on HLA-A*02:01; MAGE-A1 on HLA-A*02:01, HLA-A*01:01, or HLA-C*07:02; or MAGE-C2 on HLA-B*07:02. All TCR-Ts in the ImmunoBank and master protocol are first tested as single therapies in dose levels 1 and 2 before becoming available for multiplexing in dose levels 3 and 4. Results: From September 2023 to the time of abstract submission, 140 participants with a variety of solid tumors were enrolled in the screening protocol and are in different stages of screening. To date, 65% have ≥1 HLA match, and 20% and 6% have 2 and 3 HLA matches, respectively, highlighting the advantage of including TCR-Ts targeting multiple different HLA types within the same master protocol. Of those who have completed target screening, 92% express at least one target and 65% qualify for at least one TCR-T. Intratumoral heterogeneity of target expression was observed even with the most prevalently expressed target, PRAME, supporting the rationale for multiplexed TCR-T treatment. Although HLA-LOH affects only half of HLA genes and the remaining intact HLA alleles in tumors can still be recognized by TCR-Ts, about 13% of participants had LOH of the targeted HLA allele, excluding them from TCR-T treatment. Conclusions: Initial data indicate that the combination of HLAs and targets in the ImmunoBank results in ≥1 TCR-T match for the majority of solid tumor patients evaluated to date, and many patients qualify for multiplexed TCR-T treatment. LOH testing can prevent selection and treatment with a TCR-T that would not confer benefit. The proportion of patients eligible for multiplexing is expected to increase as the ImmunoBank grows. Updated data on screened and treated patients will be presented at the meeting. Clinical trial information: NCT05973487; NCT05812027.