Identification of Innovative Biomarkers to Predict Outcomes in Hepatocellular Carcinoma Treated With Tremelimumab and Durvalumab
For patients and families
In plain language
An automatic summary of structured registry data. It is an orientation aid, not a substitute for the official protocol or a physician assessment.
- What is being studied
- The protocol lists: blood sample.
- Who it may be relevant to
- Registry conditions: Hepatocellular Carcinoma. Basic parameters: from 18 years · All.
- What needs checking
- Age, condition and sex are only basic indicators. Prior treatment, laboratory values and other mandatory requirements appear in the eligibility criteria below.
- Where it takes place
- France
- Next step
- Save the trial, show it to the treating physician, and confirm current recruitment with the study center. Costs, documents and travel →
Unsure about the terms? Read our patient guide →
Overview
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.
Interventions
- Other 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
Primary outcome measures
- real-word overall survival [Time frame: through study completion, up to a maximum of 24 months after the inclusion of the last patient]
Secondary outcome measures (3)
- real-word progression-free-survival [Time frame: through study completion, up to a maximum of 24 months after the inclusion of the last patient]
- Objective Response Rate (ORR) [Time frame: through study completion, up to a maximum of 24 months after the inclusion of the last patient]
- Disease control rate (DCR) [Time frame: through study completion, up to a maximum of 24 months after the inclusion of the last patient]
Eligibility criteria
Inclusion criteria
- 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.
Exclusion criteria
- 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
Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.
Healthy volunteers: No
Study design
- Allocation
- N/A
- Model
- Single group
- Masking
- Open label
- Primary purpose
- Other
Study locations
France · 10 centers
- 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
- … and 2 more centers
Identifiers
NCT: NCT06796114 · 2024-931 · 2024-A02783-44