Abstract 4649
Background
Advanced hepatocellular carcinoma (HCC) is a disease of high unmet medical need. Despite considerable toxicities, sorafenib (sor) is the 1L standard of care. Single-agent inhibition of PD-L1/PD-1 or VEGF signalling has only modest activity in HCC, but in a Phase Ib study of atezolizumab (atezo; anti–PD-L1) + bevacizumab (bev; anti-VEGF) combination, a response rate of 61% with a manageable safety profile (Pishvaian ESMO 2018, submitted) is observed. Clinical benefit with atezo + bev was also seen in 1L renal cell carcinoma and 1L non-small cell lung cancer (Motzer ASCO GU 2018, Reck ESMO IO 2017). The potential synergy between atezo and bev may stem from bev’s additional immunomodulatory effects in the tumour microenvironment (increased DC maturation, enhanced T-cell infiltration, reduced MDSCs and Tregs in tumours) that may potentiate the efficacy of atezo in re-invigorating the anti-tumour T-cell response.
Trial design
IMbrave150 is a global, multicentre, randomised, open-label, Phase III trial enrolling 1L patients (pts) with locally advanced or metastatic and/or unresectable HCC. Key inclusion/exclusion criteria are shown in the table. Pts will be randomised 2:1 to receive atezo (1200 mg) plus bev (15 mg/kg) IV Q3W or sor (400 mg) PO BID until loss of clinical benefit or unacceptable toxicity. Crossover is not allowed. Stratification factors are ECOG PS (0 vs 1), baseline alpha fetoprotein level (< 400 vs ≥ 400 ng/mL), macrovascular invasion and/or extrahepatic spread (presence vs absence) and region (Asia excluding Japan vs rest of world). Co-primary endpoints are investigator (INV)–assessed ORR (RECIST v1.1) and OS, which will be tested in parallel. Secondary endpoints are INV-assessed PFS, DOR and time to progression (TTP; RECIST v1.1), along with independent review facility (IRF)–assessed ORR, PFS, DOR and TTP (RECIST v1.1 and HCC mRECIST). Approximately 480 pts will be enrolled globally.Table: 782TiP
Eligibility criteria
| Inclusion Criteria | Exclusion Criteria |
|---|---|
| - ≥ 1 measurable untreated lesion (per RECIST v1.1) - Naive to prior systemic therapy for HCC - Child-Pugh class A liver function - ECOG PS 0/1 - Adequate haematologic and end-organ function | - Co-infection of HBV and HCV - Pts with untreated varices with bleeding or high risk for bleeding - History of autoimmune disease or immune deficiency - Inadequately controlled arterial hypertension |
Clinical trial identification
NCT03434379.
Legal entity responsible for the study
F. Hoffmann-La Roche AG.
Funding
F. Hoffmann-La Roche AG.
Editorial Acknowledgement
Medical writing assistance for this abstract was provided by Steffen Biechele, PhD, of Health Interactions.
Disclosure
M.P. Ducreux: Employee: Sandoz; Honoraria: Roche/Genentech, Novartis, Ipsen, Lilly, Amgen, Servier, Merck Serono Ltd; Consulting, Advisory role: Bayer, Sirtex Medical, Lilly, Servier, Ipsen, Roche/Genentech, Amgen, Novartis, Sanofi, and Merck Serono Ltd; Research funding: Roche/Genentech, Pfizer, Merck Serono Ltd. A-L. Cheng: Consulting, Advisory role: Bayer Schering Pharma, Merck Serono Ltd, Bristol-Meyers Squibb, Onxeo, Novartis, Eisai, Ono Pharmaceutical. Speakers’ bureau for Novartis; Research funding: Sanofi. A.X. Zhu: Consulting, Advisory role: AstraZeneca, Bayer, Merck, Bristol-Meyers Squibb, Eisai, Novartis, Sanofi, Exelixis, Lilly; Research funding: Lilly, Bayer, Bristol-Meyers Squibb, Novartis, Merck. M. Ikeda: Consulting, Advisory role: NanoCarrier, Bayer Yakuhin, Eisai, Kyowa Hakko Kirin, Novartis, Shire, MSD, Bristol-Myers Squibb Japan, Teijin Pharma, Daiichi Sankyo; Honoraria: Taiho Pharmaceutical, Novartis, Bayer Yakuhin, Bristol-Myers Squibb Japan, Abbott Japan, Eisai, Lilly Japan, Chugai Pharma, Daiichi Sankyo, Otsuka, Yakult Honsha, Nobelpharma, Chugai Pharma, Dainippon Sumitomo Pharma, Teijin Pharma; Research funding: Taiho Pharmaceutical, Bayer Yakuhin, Kyowa Hakko Kirin, Yakult, Lilly Japan, Ono Pharmaceutical, Eisai, AstraZeneca, Zeria Pharmaceutical, Chugai Pharma, Bristol-Myers Squibb, Merck Serono, Kowa, NanoCarrier, Aslan Pharmaceuticals, Novartis, Takara Bio, Baxalta/Shire. D-Z. Xu; J. Liu: Employee: F. Hoffmann-La Roche Ltd. W. Verret: Employee: Roche/Genentech. R.S. Finn: Consulting, Advisory role: Pfizer, Bayer, Novartis, Bristol-Meyers Squibb, Merck, Eisai, Lilly, Roche/Genentech. Research funding: Pfizer, Bayer, Novartis, Eisai, Lilly, Merck, Bristol-Meyers Squibb. P.R. Galle: Consulting, Advisory role: Bayer, Lilly, AstraZeneca, Bristol-Meyers Squibb; Speakers’ bureau: Bayer, Sirtex Medical; Travel, accommodations, expenses: Bayer; Honoraria: Bayer, Sirtex Medical, Lilly, AstraZeneca, Bristol-Myers Squibb, Merck Sharp & Dohme, Blueprint Medicines; Research funding: Bayer. All other authors have declared no conflicts of interest.