Identification of Innovative Biomarkers to Predict Outcomes in Hepatocellular Carcinoma Treated With Tremelimumab and Durvalumab

Обзор

Several cancer immunotherapies that target the PD-L1/PD-1 pathway (i.e., checkpoint inhibitors) show promising clinical activity in patients with HCC. In particular, atezolizumab selectively targets PD-L1 to prevent interaction with receptors PD-1 and B7-1, thus reversing T-cell suppression. Moreover, atezolizumab in combination with bevacizumab, a monoclonal antibody that targets VEGF and inhibits angiogenesis, is associated with an objective response rate of 27.3% (Cheng et al. 2021; Finn et al. 2020). This tumor response has led to FDA (Food and Drug Administration) and EMA (European Medicines Agency) approvals, in first-line treatment in unresectable HCC. Combinations studies evaluating anti-CTLA4 and anti-PD1/PDL1 antibodies displayed greater benefits (Abou-Alfa et al. 2022). In the Phase 3 HIMALAYA study (NCT03298451) in uHCC, a single priming dose of tremelimumab (anti-CTLA-4) plus durvalumab (anti-PD-L1) in the STRIDE (Single Tremelimumab Regular Interval Durvalumab) regimen significantly improved OS versus sorafenib; durvalumab monotherapy was noninferior to sorafenib for OS. In the HIMALAYA study, STRIDE regimen induced long term survival (defined as the absence of progression above 36 months following inclusion) in 103 out of the 393 patients exposed to this strategy (26%). The identification of biomarkers allowing the prediction of immunotherapy efficacy in HCC is still an unmet medical need.

Вмешательства

• Другое blood sample
  A total of 48 ml of blood will be collected at baseline (before STRIDE initiation): * 6 EDTA 6 ml tubes for PBMC collection * 2 EDTA 6 ml tube for plasma collection

Первичные конечные точки

• real-word overall survival [Срок оценки: through study completion, up to a maximum of 24 months after the inclusion of the last patient]

Вторичные конечные точки (3)

• real-word progression-free-survival [Срок оценки: through study completion, up to a maximum of 24 months after the inclusion of the last patient]
• Objective Response Rate (ORR) [Срок оценки: through study completion, up to a maximum of 24 months after the inclusion of the last patient]
• Disease control rate (DCR) [Срок оценки: through study completion, up to a maximum of 24 months after the inclusion of the last patient]

Критерии участия

Критерии включения

• Signed informed consent
• Histologically confirmed hepatocellular carcinoma
• Locally advanced, metastatic, or unresectable disease
• Patient who had not previously received systemic anti-cancer treatment and are eligible to STRIDE therapy according to investigator decision in routine care and who have no contraindications to STRIDE treatment according to approved product label.
• Measurable disease defined according to RECIST v1.1 guidelines (Note: Previously irradiated lesions can be considered as measurable disease only if disease progression has been unequivocally documented at that site since radiation.)
• Age ≥ 18 years
• Patient affiliated to or beneficiary of French social security system
• Ability to comply with the study protocol, in the Investigator's judgment.

Критерии исключения

• Patients previously exposed to anti-tumor immunotherapy as anti-PD-1, anti-PD-L1, or anti-CTLA4 agent or any immune therapy.
• Patient with any medical or psychiatric condition or disease, which would make the patient inappropriate for entry into this study
• Patient under guardianship, curatorship or under the protection of justice

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Не применимо

Модель

Одна группа

Маскирование

Открытое

Основная цель

Другое

Центры проведения

Франция · 10 центров

• CHU de Besançon — Besançon
• CH de Chalon sur Saône — Chalon-sur-Saône
• CHU Grenoble — Grenoble
• CH de Mulhouse — Mulhouse
• Hôpital Beaujon - APHP — Paris
• Hôpital Henri Mondor - APHP — Paris
• Hôpital La Pitié Salpêtrière - APHP — Paris
• CHU Poitiers — Poitiers
• … и ещё 2 центра

Идентификаторы

NCT: NCT06796114 · 2024-931 · 2024-A02783-44

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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