First Patient Receives TCR-T Therapy in Multiplexed Study Screening Patients With Melanoma, Cervical Cancer and More

Screening is underway for participants with solid tumors to receive T-Plex, a multiplexed T-cell receptor-engineered T-cell (TCR-T) therapy, with 1 participant having received 1 Singleplex therapy so far in a phase 1 study (NCT05973487) with no acute toxicities.

Data from the TSCAN-003 screening study (NCT05812027) and initial data from the phase 1 study were presented at the 2024 American Society of Clinical Oncology (ASCO) Annual Meeting, held May 31 - June 4, in Chicago, Illinois, by Dawn Pinchasik, MD, MS, vice president, clinical development, TScan Therapeutics.

“Advanced solid tumor malignancies have been difficult to conquer due to complex tumor biology. This includes factors such as tumorheterogeneity, a lack of endogenousT-cells targeting tumor antigens, and an immunosuppressive tumor microenvironment. Loss of heterozygosity (LOH) has also been identified in up to 40% of solid tumors,” Pinchasik said during her presentation.

TSCAN-002 is a master protocol currently containing 6 TCR-Ts from a growing collection of TCR-Ts, called the ImmunoBank. Three TCR-Ts target MAGE-A1 across different HLA types, one targets MAGE-C2, one targets PRAME, and one targets HPV16. Each TCR-T is first evaluated as Singleplex therapy up to dose level, then is available for multiplexing for any other TCR-T that has also cleared dose level 2. The multiplexing of TCR-Ts is known as T-Plex.

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There are currently 6 Singleplex cohorts open to enrollment in the master protocol, with participants in dose levels 1 and 2 receiving a single TCR-T infusion after lymphodepletion and participants in dose levels 3 and 4 receiving another infusion around 28 days later. In the T-Plex cohorts, the infusions will be of 2 different TCR-Ts.

The TSCAN-003 screening study has enrolled over 300 participants since September 2023. Over 75% of participants have melanoma, head and neck cancer, non-small lung cancer, or ovarian cancer. Cervical, uterine, anogenital, and soft tissue sarcoma cancers are also represented. The study screens patients for a match to one of the 4 TCR-Ts in the ImmunoBank. Of the enrolled participants so far, 71% had at least one HLA match in the ImmunoBank, and of these, 68 have passed the screening for target expression and LOH. Of the 68, 73% have at least 1 TCR-T match and 27% have more than 1 TCR-T match, qualifying for T-Plex therapy.

“The proportion of participants who qualify for T-Plex is expected to increase as the ImmunoBank grows via additional investigational new drug applications. Perspective testing for LOH has enabled assignment only to TCR-T cohorts that have target expressed by intact HLAs,” Pinchasik said.

The first participant in the treatment study enrolled received TSC-203A0201 targeting PRAME for the treatment of metastatic cutaneous melanoma and has experienced no acute toxicities so far. Manufacturing is underway for an additional 3 participants.

REFERENCE

Thomas SS, Pico B, Henick BS, et al. Initial data from a phase 1, first-in-human clinical trial for T-Plex, a multiplexed, enhanced T cell receptor-engineered T cell therapy (TCR-T) for solid tumors. Presented at: 2024 (ASCO) Annual Meeting; May 31 - June 4; Chicago, Illinois. Poster #21.