Characteristics of Long-term Survivors to Tremelimumab plus Durvalumab Therapy for HCC

JRCT ID: jRCT1061240056

Registered date:17/09/2024

Basic Information

• Recruitment status: Recruiting
• Health condition(s) or Problem(s) studied: Hepatocellular Carcinoma
• Date of first enrollment: 17/09/2024
• Target sample size: 20
• Study type: Observational

Outcome(s)

• Primary Outcome: The hypothesis is that the maintenance of TCR repertoire changes in early T cells during treatment may contribute to long-term survival. The study aims to evaluate the potential long-term efficacy of Tremelimumab plus Durvalumab treatment for HCC by sequentially examining the TCR repertoire changes in peripheral blood T cells during the early stage of treatment (up to 4 weeks). The study will also compare the TCR repertoire changes at the early stage of treatment with those at 6 months or at PD after treatment initiation, whichever happens first,, assuming that the changes in the potential long-term survival group (defined as survivors at 24 months after the initiation of the therapy) would persist in the long term. This comparison will be conducted between the potential long-term survival group and the non potential long-term survival group.

Secondary Outcome

1. Identification of the characteristics of the long-term survival group at 24 months after treatment initiation through the analysis of PD-L1 expression on extracellular vesicles derived from cancer cells in peripheral blood in the period before treatment initiation, during early treatment (up to 4 weeks), and at 6 months or at PD after treatment initiation, whichever happens first.
2. Association analysis between the expression state of various molecules such as PD-1, TIM-3, TIGIT and CD28 in T cells, the frequency of regulatory T cells, and their changes in peripheral blood mononuclear cells (PBMCs) at the time of treatment initiation, during early treatment (up to 4 weeks), and at 6 months or at PD after treatment initiation, whichever happens first, and potential long term survival.
3. Determining the expression levels and changes over time in immune checkpoint-related molecules, such as CTLA-4, GITR, ICOS, TIM-3, TIGIT, CD106, on extracellular vesicles derived from cells in blood at baseline, early treatment (up to 4 weeks), and 6 months or at PD after treatment initiation, whichever happens first.
4. For the five cases in which liver tissue examination before treatment is possible, determining the expression of immune regulatory molecules on CD155 in HCC tissue using scRNAseq, and data obtained from extracellular vesicles in blood.
5. Determining the levels of extracellular vesicles derived from HCC cells in blood at baseline, early treatment (up to 4 weeks), and 6 months or at PD after treatment initiation, whichever happens first.
6. For the five cases in which liver tissue examination before treatment is possible, scRNA/TCRseq analysis of HCC tissue before treatment will be performed in conjunction with analysis of peripheral blood. The association between the state of T cells and the anti-tumor immune status within the cancer tissue will be investigated and, to examine TCR repertoire changes in blood over time from baseline to 6mo or PD at single-cell level, scRNAseq/TCRseq will be done.
7. The association between the Grade 3 or higher imAE occurrence and the state of T cells will be also determined.

Key inclusion & exclusion criteria

• Age minimum: >= 18age old
• Age maximum: < 80age old
• Gender: Both

Include criteria

1. Patients with unresectable HCC receiving Tremelimumab plus Durvalumab as first-line therapy (including those who participate in other observational studies but can provide the samples required for this study).
2. Patients who are able to provide written consent for participation in the study based on their free will.
3. Patients who are between the ages of 18 and 80 at the time of consent.

Exclude criteria

1. Patients who cannot complete at least two cycles of STRIDE regimen as first-line therapy.
2. Patients who previously received immunotherapy.
3. Patients whose tumor status cannot be judged by imaging modalities.

Related Information

• Primary Sponsor: OTSUKA MOTOYKI
• Source(s) of Monetary Support: AstraZeneca