206TiP - SIERRA: A phase IIIb, single-arm, multicentre study of tremelimumab plus durvalumab for first-line treatment of advanced unresectable hepatocellular carcinoma

Background

Hepatocellular carcinoma (HCC) is the most common type of liver cancer and is frequently diagnosed at an advanced stage. In the phase 3 HIMALAYA study (NCT03298451) in unresectable HCC (uHCC), the STRIDE (Single Tremelimumab Regular Interval Durvalumab) regimen improved overall survival (OS) versus sorafenib, with a manageable safety profile. HIMALAYA enrolled participants with uHCC not eligible for embolisation with Barcelona Clinic Liver Cancer (BCLC) stage B or C, Child-Pugh (CP) class A, WHO/ECOG PS of 0-1 and no main trunk portal vein thrombosis (PVT). Based on the positive results of HIMALAYA, the aim of SIERRA is to assess the safety and efficacy of STRIDE in a broader uHCC population, including inferior hepatic function, poorer performance status or more advanced disease.

Trial design

SIERRA (NCT05883644) is a phase 3b, single-arm, multicentre study. This study will enroll approximately 140 adults with uHCC, BCLC stage B or C, and one of the following: CP class of B7 or B8 with WHO/ECOG PS of 0-1, without main trunk PVT; CP class A with WHO/ECOG PS of 2, without main trunk PVT; CP class A with WHO/ECOG PS of 0-1 with evidence of chronic main trunk PVT. Participants must not have received prior systemic therapy for HCC and must not be eligible for locoregional therapy. Key exclusion criteria include evidence of acute main trunk PVT. All participants will receive STRIDE: one single priming dose of 300 mg tremelimumab plus 1500 mg durvalumab at Day 1 (Week 0), followed by durvalumab 1500 mg monotherapy Q4W starting at Week 4 and continuing until clinical progression, confirmed radiological progression (RECIST 1.1), unacceptable toxicity, withdrawal of consent or any discontinuation criteria are met. The co-primary endpoints are the incidence of Grade 3 or 4 adverse events possibly related to study intervention within 6 months after initiation of STRIDE and investigator-assessed (RECIST 1.1) objective response rate. Secondary endpoints include OS, progression-free survival, duration of response and health-related quality of life. Enrolment has begun and will proceed in France, Germany, Italy, Japan, South Korea, Singapore, Spain, United States, Vietnam and Hong Kong.

Clinical trial identification

NCT05883644.

Legal entity responsible for the study

AstraZeneca.

Funding

AstraZeneca.

Disclosure

S.L. Chan: Financial Interests, Personal, Advisory Board: Eisai, AstraZeneca, MSD, BMS, Roche; Financial Interests, Personal, Invited Speaker: AstraZeneca, MSD, Eisai, Roche, Ipsen, BMS; Financial Interests, Personal, Research Grant: Eisai, MSD. B. Sangro: Financial Interests, Personal, Advisory Board: AstraZeneca, BMS, Boston Scientific, Roche, Sirtex, Terumo, Bayer, Adaptimmune; Financial Interests, Personal, Invited Speaker: Roche, Sirtex, Eisai, Ipsen, Incyte, AstraZeneca, Astellas Pharma; Financial Interests, Institutional, Research Grant: BMS, Sirtex; Financial Interests, Personal, Coordinating PI: AstraZeneca; Financial Interests, Personal, Steering Committee Member: BMS, Boston Scientific, Roche. M. Kudo: Financial Interests, Personal, Invited Speaker: Eisai, Chugai, Eli Liiy, Bayer, Takeda, AstraZeneca; Financial Interests, Institutional, Research Grant: Otsuka, EA Pharma, Taiho, Eisai, AbbVie, GE Healthcare, Chugai. A. Dane: Financial Interests, Institutional, Speaker, Consultant, Advisor: Adagio, Amplyx, AN2, Bioscript, Bugworks, CARBX, Closed Loop Medicine, Correvio, Davolterra, Destiny, Evopoint, F2G, Entasis, Gates, GSK, Humanigen, Liverpool University, Kymab, Melinta, Modis, Orca, Phico, Quince, Roche, SFunga, Scynexis, Sinovent, SNIPR; Financial Interests, Institutional, Other, Independent statistician on DSMBs: Aridis, Cerium, ContraFect, Egetis, Midatech, Pfizer, Pled, Rare Thyroid, Sanofi, Transcrip. C. Emery: Financial Interests, Personal, Other, Contracted employee: AstraZeneca. M. Paskow: Financial Interests, Personal, Full or part-time Employment: AstraZeneca; Financial Interests, Personal, Stocks/Shares: AstraZeneca. M. Makowsky: Financial Interests, Personal, Full or part-time Employment: AstraZeneca; Financial Interests, Personal, Stocks/Shares: AstraZeneca. B. Nguyen: Financial Interests, Personal, Full or part-time Employment: AstraZeneca. L. Rimassa: Financial Interests, Personal, Advisory Board, Consulting and advisory role: AstraZeneca, Basilea, Bayer, Exelixis, Genenta, Hengrui, Incyte, Ipsen, IQVIA, Jazz Pharmaceuticals, MSD, Nerviano Medical Sciences, Roche, Servier, Taiho Oncology, Zymeworks; Financial Interests, Personal, Invited Speaker, Lecture fees: AstraZeneca, Bayer, BMS, Incyte, Ipsen, Roche, Servier; Financial Interests, Personal, Other, Travel expenses: AstraZeneca; Financial Interests, Institutional, Steering Committee Member: Exelixis, Incyte, Ipsen, Nerviano Medical Sciences, Roche; Financial Interests, Institutional, Coordinating PI, National (Italian) coordinating PI: AstraZeneca, BeiGene, Zymeworks; Financial Interests, Institutional, Local PI: Agios, Eisai, Fibrogen, Lilly, MSD; Financial Interests, Institutional, Funding: Ipsen; Financial Interests, Institutional, Coordinating PI, European PI: AstraZeneca.