LBA3IMbrave150: Efficacy and safety results from a ph III study evaluating atezolizumab (atezo) + bevacizumab (bev) vs sorafenib (Sor) as first treatment (tx) for patients (pts) with unresectable hepatocellular carcinoma (HCC).

Background Ph 1b data has shown promising efficacy and safety for atezo + bev in unresectable HCC pts who have not received prior systemic therapy. Here, we report the primary analysis data from the Ph 3 IMbrave150 trial comparing atezo + bev vs sor in this pt population. Methods IMbrave150 enrolled systemic treatment (tx)-naïve pts with unresectable HCC. Pts were randomised 2:1 to receive either atezo 1200 mg IV q3w + bev 15 mg/kg IV q3w or sor 400 mg BID until unacceptable toxicity or loss of clinical benefit per investigator. Coprimary endpoints were OS and PFS by independent review facility (IRF)-assessed RECIST 1.1. The key secondary endpoints IRF-ORR per RECIST 1.1 and IRF-ORR per HCC mRECIST were also part of the study statistical testing hierarchy. Results The ITT population included 336 pts randomised to atezo + bev and 165 randomised to sor. Baseline demographics were well balanced between arms. With a median follow up of 8.6 mo, OS HR was 0.58 (95% CI, 0.42, 0.79; P = 0.0006) and PFS HR was 0.59 (95% CI, 0.47, 0.76; P < 0.0001; see table) for atezo + bev vs sor. ORR was 27% vs 12% (P < 0.0001) per IRF RECIST 1.1 and 33% vs 13% (P < 0.0001) per IRF HCC mRECIST for atezo + bev vs sor, respectively. Results were generally consistent across clinical subgroups. Atezo + bev delayed deterioration of quality of life vs sor. Median tx duration was 7.4 mo for atezo, 6.9 for bev and 2.8 for sor. Grade 3-4 AEs occurred in 57% of pts receiving atezo + bev and 55% of pts receiving sor. Grade 5 AEs were seen in 5% and 6% of pts, respectively. Conclusions IMbrave150 demonstrated statistically significant and clinically meaningful improvement in both OS and PFS for atezo + bev vs sor in pts with unresectable HCC who have not received prior systemic therapy. The safety of atezo + bev is consistent with the known safety profile of each agent, and no new safety signals were identified. Atezo + bev has the potential to be a practice changing tx in HCC. Clinical trial identification NCT03434379. Editorial acknowledgement Medical writing assistance for this abstract was provided by Jessica Bessler, PhD, of Health Interactions, Ltd. and funded by F. Hoffmann-La Roche, Ltd. Legal entity responsible for the study F. Hoffmann-La Roche, Ltd. Funding F. Hoffmann-La Roche, Ltd. Table: LBA3 Coprimary endpoints  Atezo + bev n = 336  Sor n = 165  OS  Median, mo 95% CI  NE  13.2 (10.4, NE)  HR a 95% CI  0.58 (0.42, 0.79)  P value a,b   0.0006  PFS  Median, mo 95% CI  6.8 (5.7, 8.3)  4.3 (4.0, 5.6)  HR a 95% CI  0.59 (0.47, 0.76)  P value a,b   <0.0001  Coprimary endpoints  Atezo + bev n = 336  Sor n = 165  OS  Median, mo 95% CI  NE  13.2 (10.4, NE)  HR a 95% CI  0.58 (0.42, 0.79)  P value a,b   0.0006  PFS  Median, mo 95% CI  6.8 (5.7, 8.3)  4.3 (4.0, 5.6)  HR a 95% CI  0.59 (0.47, 0.76)  P value a,b   <0.0001  NE, non-estimable. a Stratified analysis. b Log rank. Table: LBA3 Coprimary endpoints  Atezo + bev n = 336  Sor n = 165  OS  Median, mo 95% CI  NE  13.2 (10.4, NE)  HR a 95% CI  0.58 (0.42, 0.79)  P value a,b   0.0006  PFS  Median, mo 95% CI  6.8 (5.7, 8.3)  4.3 (4.0, 5.6)  HR a 95% CI  0.59 (0.47, 0.76)  P value a,b   <0.0001  Coprimary endpoints  Atezo + bev n = 336  Sor n = 165  OS  Median, mo 95% CI  NE  13.2 (10.4, NE)  HR a 95% CI  0.58 (0.42, 0.79)  P value a,b   0.0006  PFS  Median, mo 95% CI  6.8 (5.7, 8.3)  4.3 (4.0, 5.6)  HR a 95% CI  0.59 (0.47, 0.76)  P value a,b   <0.0001  NE, non-estimable. a Stratified analysis. b Log rank. Disclosure A-L. Cheng: Advisory / Consultancy: Bayer Schering Pharma; Advisory / Consultancy: Bristol-Myers Squibb; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Eisai; Advisory / Consultancy: Merck Serono; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Novartis; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Ono Pharmaceutical; Advisory / Consultancy: Exelixis; Advisory / Consultancy: Nucleix Ltd.; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Roche/Genentech; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: IQVIA; Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Bayer Yakuhin, Ltd; Speaker Bureau / Expert testimony: Amgen Taiwan; Honoraria (self): Bayer; Honoraria (self): Merck Sharp Dohme; Honoraria (self): Merck Serono. M. Ikeda: Honoraria (self): Abbott Japan; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): Bayer Yakuhin; Advisory / Consultancy, Research grant / Funding (institution): Bristol-Myers Squibb; Honoraria (self): Bristol-Myers Squibb Japan; Honoraria (self), Research grant / Funding (institution): Chugai Pharma; Honoraria (self), Research grant / Funding (institution): Daiichi Sankyo; Honoraria (self), Honoraria (institution), Research grant / Funding (institution): Eisai; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): Lilly Japan; Honoraria (self): Nippon Kayaku; Honoraria (self): Novartis; Honoraria (self), Research grant / Funding (institution): Taiho Pharmaceutical; Advisory / Consultancy, Research grant / Funding (institution): Kyowa Hakko Kirin; Advisory / Consultancy, Research grant / Funding (institution): NanoCarrier; Research grant / Funding (self): ASLAN Pharmaceuticals; Research grant / Funding (self): AstraZeneca; Research grant / Funding (self): Baxter; Research grant / Funding (self): Boehringer Ingelheim; Research grant / Funding (self): Kowa; Research grant / Funding (self): Merck Serono; Research grant / Funding (self): Ono Pharmaceutical, Yakult, Zeria Pharmaceutical. P.R. Galle: Honoraria (self), Research grant / Funding (institution): Bayer; Honoraria (self): Bristol-Myers Squibb; Honoraria (self): MSD; Honoraria (self): AstraZeneca; Honoraria (self): SIRTEX; Honoraria (self): Merck; Honoraria (self): Lilly; Honoraria (self): Blueprint; Honoraria (self): AdaptImmune; Honoraria (self): Eisai; Honoraria (self): Roche; Honoraria (self): Ipsen. M.P. Ducreux: Honoraria (self), Advisory / Consultancy: Lilly; Honoraria (self), Advisory / Consultancy: Servier; Advisory / Consultancy: Amgen; Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Celgene; Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Ipsen; Advisory / Consultancy, Travel / Accommodation / Expenses: Merck Serono; Advisory / Consultancy: Novartis; Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (self), Travel / Accommodation / Expenses: Roche; Speaker Bureau / Expert testimony: Bayer; Speaker Bureau / Expert testimony: Merck KGaA; Research grant / Funding (self): Pfizer; Spouse / Financial dependant: Sandoz. A.X. Zhu: Advisory / Consultancy: AstraZeneca; Advisory / Consultancy, Research grant / Funding (institution): Bayer; Advisory / Consultancy, Research grant / Funding (institution): Bristol-Myers Squibb; Advisory / Consultancy: Eisai; Advisory / Consultancy: Exelixis; Advisory / Consultancy, Research grant / Funding (institution): Lilly; Advisory / Consultancy, Research grant / Funding (institution): Merck; Advisory / Consultancy, Research grant / Funding (institution): Novartis; Advisory / Consultancy: Roche/Genentech. M. Kudo: Honoraria (self), Research grant / Funding (institution): AbbVie; Honoraria (self), Advisory / Consultancy: Bayer; Honoraria (self), Research grant / Funding (institution): Bristol-Myers Squibb Japan; Honoraria (self): EA Pharma; Honoraria (self), Advisory / Consultancy: Eisai; Honoraria (self): Gilead Sciences; Honoraria (self): Merck Serono; Honoraria (self), Advisory / Consultancy: MSD; Honoraria (self): Novartis; Honoraria (self): Pfizer; Honoraria (self), Research grant / Funding (institution): Taiho Pharmaceutical; Advisory / Consultancy: Bristol-Myers Squibb; Research grant / Funding (institution): Astellas Pharma; Research grant / Funding (institution): Chugai Pharma; Research grant / Funding (institution): Daiichi Sankyo; Research grant / Funding (institution): Otsuka. V. Breder: Honoraria (self), Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Bayer; Honoraria (self), Advisory / Consultancy: BioCad; Honoraria (self), Advisory / Consultancy: Boehringer Ingelheim; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Bristol-Myers Squibb; Honoraria (self), Advisory / Consultancy: Eisai; Honoraria (self), Advisory / Consultancy: MSD Oncology; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Roche; Honoraria (self), Travel / Accommodation / Expenses: Takeda. P. Merle: Research grant / Funding (self): ONXEO; Advisory / Consultancy, Travel / Accommodation / Expenses: Bayer; Advisory / Consultancy, Travel / Accommodation / Expenses: Ipsen; Advisory / Consultancy: Eisai; Advisory / Consultancy, Travel / Accommodation / Expenses: Roche; Advisory / Consultancy, Travel / Accommodation / Expenses: MSD; Travel / Accommodation / Expenses: Bristol-Myers Squibb. A. Kaseb: Shareholder / Stockholder / Stock options: Gilead Sciences; Honoraria (self), Advisory / Consultancy: Bayer Health; Honoraria (self), Advisory / Consultancy, Research grant / Funding (self), Travel / Accommodation / Expenses: Bristol-Myers Squibb; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Exelixis; Honoraria (self), Advisory / Consultancy, Research grant / Funding (self), Travel / Accommodation / Expenses: Merck; Research grant / Funding (self): Genentech; Research grant / Funding (self), Travel / Accommodation / Expenses: Bayer/Onyx. D. Li: Advisory / Consultancy: Bayer; Advisory / Consultancy, Speaker Bureau / Expert testimony: Exelixis; Advisory / Consultancy, Speaker Bureau / Expert testimony: Ipsen; Honoraria (institution), Speaker Bureau / Expert testimony: Lexicon; Advisory / Consultancy: Novartis; Speaker Bureau / Expert testimony: Advanced Accelerator Applications. W. Verret: Full / Part-time employment: Genentech. Z.D. Xu: Full / Part-time employment: Roche. S. Hernandez: Shareholder / Stockholder / Stock options, Full / Part-time employment: Genentech. J. Liu: Full / Part-time employment: Roche. C. Huang: Full / Part-time employment: Roche. S. Mulla: Full / Part-time employment: Roche. R. Finn: Advisory / Consultancy: AstraZeneca; Advisory / Consultancy: Bayer; Advisory / Consultancy: BristolMyersSquibb; Advisory / Consultancy: Eisai; Advisory / Consultancy: Eli Lilly; Advisory / Consultancy: Merck; Advisory / Consultancy: Pfizer; Advisory / Consultancy: Roche/Genentech; Speaker Bureau / Expert testimony: Novartis. [ABSTRACT FROM AUTHOR]