Abstract 206TiP
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.
Resources from the same session
62P - Combination of chemotherapy with endocrinal therapy as upfront treatment of metastatic breast cancer in hormone receptor- positive, HER2 -negative disease: A phase II randomised clinical trial
Presenter: Mariam Saleh
Session: Poster Display
Resources:
Abstract
63P - Efficacy and safety of eribulin plus carboplatin combination for HER2-negative metastatic breast cancer
Presenter: Mengqian Ni
Session: Poster Display
Resources:
Abstract
64P - Unmet needs following metastatic breast cancer in a middle-income Asian country
Presenter: Nirmala Bhoo-Pathy
Session: Poster Display
Resources:
Abstract
66P - Utidelone-based therapy in metastatic solid tumors after failure of standard therapies: A prospective, multicenter, single-arm trial
Presenter: Jianjun Zhang
Session: Poster Display
Resources:
Abstract
67P - Efficacy and safety of trastuzumab biosimilar in HER2+ve metastatic breast cancer: A multicenter phase III study
Presenter: krishna Mohan
Session: Poster Display
Resources:
Abstract
68P - Neratinib in combination with fulvestrant and or palbociclib can overcome endocrine resistance in HER2-low/ ER+ breast cancer
Presenter: Maryam Arshad
Session: Poster Display
Resources:
Abstract
69P - A multicenter, retrospective, real-world study of inetetamab combined with pyrotinib and vinorelbine as treatment for HER2-positive metastatic breast cancer
Presenter: Nan Jin
Session: Poster Display
Resources:
Abstract
70P - Overall survival of eribulin, trastuzumab, and pertuzumab as first-line therapy for patients with HER2-positive metastatic breast cancer: A phase II, single-arm clinical trial
Presenter: Kenichi Inoue
Session: Poster Display
Resources:
Abstract
71P - Efficacy and safety of disitamab vedotin after trastuzumab for HER2 -positive breast cancer: A real-world data of retrospective study
Presenter: Chao Li
Session: Poster Display
Resources:
Abstract
72P - Real-world data on the efficacy of T-DM1 biosimilar for the treatment of HER2-positive metastatic breast cancer patients: Outcomes from a single center retrospective study in India
Presenter: Kaushal Patel
Session: Poster Display
Resources:
Abstract