Hepatocellular Carcinoma
Conditions
Keywords
biomarker, immunotherapy
Brief summary
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
OTHERblood 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
Sponsors
Centre Hospitalier Universitaire de Besancon
AstraZeneca
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
OTHER
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Signed informed consent 2. Histologically confirmed hepatocellular carcinoma 3. Locally advanced, metastatic, or unresectable disease 4. 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. 5. 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.) 6. Age ≥ 18 years 7. Patient affiliated to or beneficiary of French social security system 8. Ability to comply with the study protocol, in the Investigator's judgment.
Exclusion criteria
1. Patients previously exposed to anti-tumor immunotherapy as anti-PD-1, anti-PD-L1, or anti-CTLA4 agent or any immune therapy. 2. Patient with any medical or psychiatric condition or disease, which would make the patient inappropriate for entry into this study 3. Patient under guardianship, curatorship or under the protection of justice
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| real-word overall survival | through study completion, up to a maximum of 24 months after the inclusion of the last patient | defined as the delay from the date of treatment initiation to death from any cause |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| real-word progression-free-survival | through study completion, up to a maximum of 24 months after the inclusion of the last patient | defined as the delay from the date of treatment initiation to the disease progression or death from any cause whichever occurs first, evaluated by RECIST criteria v1.1 and mRECIST. |
| Objective Response Rate (ORR) | through study completion, up to a maximum of 24 months after the inclusion of the last patient | defined as the addition of complete response and partial response rates, evaluated by RECIST citeria v1.1 and mRECIST |
| Disease control rate (DCR) | through study completion, up to a maximum of 24 months after the inclusion of the last patient | defined as the addition of complete response, partial response, and stable disease rates evaluated by RECIST criteria v1.1 and mRECIST. |
Countries
France
Contacts
CONTACTAngélique VIENOT, Dr
Outcome results
None listed