Clinical trial NCT06796114: Identification of Innovative Biomarkers to Predict Outcomes in Hepatocellular Carcinoma Treated With Tremelimumab and Durvalumab
Official title: Identification of Innovative Biomarkers to Predict Outcomes in Hepatocellular Carcinoma Treated With Tremelimumab and Durvalumab
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: NA
Conditions: Hepatocellular Carcinoma
Keywords: biomarker, immunotherapy
Lead sponsor: Centre Hospitalier Universitaire de Besancon
Sponsor class: OTHER
Collaborators: name: AstraZeneca
First posted: 2025-01-28
Enrollment: 120
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: OTHER

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.


Eligibility criteria: 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

Primary outcomes:
measure: real-word overall survival
timeFrame: through study completion, up to a maximum of 24 months after the inclusion of the last patient
Secondary outcomes:
measure: real-word progression-free-survival
timeFrame: through study completion, up to a maximum of 24 months after the inclusion of the last patient
measure: Objective Response Rate (ORR)
timeFrame: through study completion, up to a maximum of 24 months after the inclusion of the last patient
measure: Disease control rate (DCR)
timeFrame: through study completion, up to a maximum of 24 months after the inclusion of the last patient
Other outcomes:
Locations:
city: Besancon
country: France
facility: CHU de Besançon
city: Chalon-sur-Saône
country: France
facility: CH de Chalon sur Saône
city: Grenoble
country: France
facility: CHU Grenoble
city: Mulhouse
country: France
facility: CH de Mulhouse
city: Paris
country: France
facility: Hôpital Beaujon - APHP
city: Paris
country: France
facility: Hôpital Henri Mondor - APHP
city: Paris
country: France
facility: Hôpital La Pitié Salpêtrière - APHP
city: Strasbourg
country: France
facility: ICANS
Study officials:
References: