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267 Background: Atezo + bev has been approved globally for pts with unresectable HCC who have not received prior systemic therapy, based on results from IMbrave150 (NCT03434379). At a median of 8.6 mo follow-up, both coprimary endpoints were met, with statistically significant and clinically meaningful improvements observed with atezo + bev vs sor for OS (HR, 0.58 [95% CI, 0.42, 0.79]; P<0.001) and independently-assessed progression-free survival (PFS; per RECIST 1.1; HR, 0.59 [95% CI, 0.47, 0.76]; P<0.001) (Finn, et al. N Engl J Med 2020). Here, we report an updated OS analysis for IMbrave150. Methods: The global, multicenter, randomized, open-label, Phase III study IMbrave150 enrolled 501 systemic treatment–naive pts with unresectable HCC, ≥1 measurable untreated lesion (RECIST 1.1), Child-Pugh class A liver function and ECOG PS 0/1. Pts were randomized 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. This post hoc, descriptive OS analysis was conducted with 12 mo of additional follow up from the primary analysis. Results: 501 pts were enrolled, including 336 to atezo + bev and 165 to sor. At the clinical cut-off date of Aug 31, 2020, median follow-up was 15.6 mo and 280 OS events were observed. Median OS was 19.2 mo with atezo + bev vs 13.4 mo with sor (HR, 0.66 [95% CI, 0.52, 0.85]; P=0.0009). Survival at 18 mo was 52% with atezo + bev and 40% with sor. Survival benefit with atezo + bev over sor was generally consistent across subgroups and with the primary analysis. The updated objective response rate (ORR; 29.8% per RECIST 1.1) with atezo + bev was in line with the primary analysis, with more pts achieving complete response (CR; 7.7%) than previously reported. Additional response data are in Table. Safety was aligned with the primary analysis, with no new signals identified. Conclusions: IMbrave150 showed consistent clinically meaningful treatment benefit and safety with 12 mo of additional follow-up. The combination provides the longest survival seen in a front-line Phase III study in advanced HCC, confirming atezo + bev as a standard of care for previously untreated, unresectable HCC. Clinical trial information: NCT03434379. [Table: see text]

<b><i>Introduction:</i></b> Atezolizumab plus bevacizumab significantly improved overall survival (OS) and progression-free survival (PFS) versus sorafenib in patients with unresectable hepatocellular carcinoma (HCC) in IMbrave150. Efficacy and safety data from the Chinese subpopulation are reported. <b><i>Methods:</i></b> IMbrave150, a global, randomized, open-label, phase 3 study in patients with systemic treatment-naive unresectable HCC, included an extension phase that enrolled additional patients from mainland China. Patients were randomized (2:1) to receive intravenous atezolizumab 1,200 mg plus bevacizumab 15 mg/kg once every 3 weeks or sorafenib 400 mg twice a day until unacceptable toxicity or loss of clinical benefit. Co-primary endpoints were OS and independent review facility-assessed PFS per Response Evaluation Criteria in Solid Tumors version 1.1 in the intention-to-treat population. <b><i>Results:</i></b> Of 194 Chinese patients enrolled from April 16, 2018, to April 8, 2019 (137 in the global study and 57 in the China extension phase), 133 received atezolizumab plus bevacizumab and 61 received sorafenib. At the data cutoff (August 29, 2019), the stratified hazard ratio for OS was 0.44 (95% CI, 0.25–0.76) and for PFS was 0.60 (95% CI, 0.40–0.90). The respective median OS and PFS with atezolizumab plus bevacizumab were not reached (NR; 95% CI, 13.5 months to NR) and 5.7 months (95% CI, 4.2–8.3) versus 11.4 months (95% CI, 6.7 to NR) and 3.2 months (95% CI, 2.6–4.8) with sorafenib. Grade 3–4 adverse events (AEs) occurred in 78 of 132 (59.1%) atezolizumab plus bevacizumab-treated and 27 of 58 (46.6%) sorafenib-treated patients. The most common grade 3–4 AE with atezolizumab plus bevacizumab was hypertension, occurring in 15.2% of patients; however, other high-grade AEs were infrequent. <b><i>Conclusion:</i></b> Clinically meaningful improvements in OS and PFS observed with atezolizumab plus bevacizumab versus sorafenib suggest that atezolizumab plus bevacizumab may become a practice-changing treatment for Chinese patients with unresectable HCC.

4073 Background: Atezo + bev has been approved in >60 countries for pts with unresectable HCC who have not received prior systemic therapy, based on IMbrave150 (NCT03434379; Finn RS NEJM 2020). Due to their poor prognosis and the hemodynamic changes from increased portal vein pressure, pts with main portal vein tumor thrombus are often excluded from pivotal HCC trials. Here, we report exploratory efficacy and safety results of pts with Vp4 (presence of a tumor thrombus in the main trunk and/or contralateral portal vein) using updated IMbrave150 data (Finn RS ASCO GI 2021). Methods: Pts were randomized 2:1 to 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. IMbrave150 enrolled 501 systemic treatment (tx)–naive unresectable HCC pts, ≥1 measurable untreated lesion (RECIST 1.1), Child-Pugh class A liver function and ECOG PS 0/1, including 73 (15%) Vp4 pts. This post hoc exploratory analysis was conducted with a median follow-up of 15.6 mo in ITT pts. Results: Of the Vp4 pts, 48 received atezo + bev and 25 received sor. Median OS (mOS) was 7.6 vs 5.5 mo (HR, 0.62; 95% CI: 0.34, 1.11) and median PFS (mPFS) per independent review facility (IRF)–assessed RECIST 1.1 was 5.4 vs 2.8 mo (HR, 0.62; 95% CI: 0.35, 1.09) with atezo + bev and sor, respectively. ORR per IRF RECIST 1.1 was 23% (11/47) with atezo + bev (2 [4%] pts had CR) vs 13% (3/23) with sor (1 [4%] pt had CR). All-grade variceal bleeding was higher with atezo + bev in Vp4 (13.6%) vs rest of ITT pts (2.5%). See table for further efficacy and safety data. Conclusions: The benefits of atezo + bev over sor in Vp4 pts are consistent with those in ITT pts across all efficacy endpoints, despite the expected disease-intrinsic increase in variceal bleeding in Vp4 vs rest of ITT pts. The overall positive benefit-risk profile supports the use of atezo + bev in pts with Vp4. Clinical trial information: NCT03434379. [Table: see text]

Background Emicizumab is a subcutaneously administered humanized, bispecific, monoclonal antibody approved for prophylaxis in people with hemophilia A. Methods HAVEN 5 (NCT03315455) is a randomized, open‐label, phase 3 study of individuals aged ≥12 years with severe hemophilia A without factor VIII (FVIII) inhibitors, or hemophilia A of any severity with FVIII inhibitors, across the Asia‐Pacific region. Participants were randomly assigned (2:2:1) to receive emicizumab 1.5 mg/kg once weekly (arm A), emicizumab 6 mg/kg every 4 weeks (arm B), or no prophylaxis (arm C). The primary end point was annualized bleeding rate (ABR) for treated bleeds; ABRs were compared between people receiving emicizumab prophylaxis versus those with no prophylaxis. Secondary end points included ABR for treated target joint bleeds. Safety was also evaluated. Results From April 26, 2018, to January 4, 2019, 70 of 76 screened participants were enrolled and randomized (arm A, n = 29; arm B, n = 27; arm C, n = 14). ABRs (95% confidence interval) for treated bleeds and treated target joint bleeds, respectively, were: arm A, 1.0 (0.53‐1.85) and 0.4 (0.18‐1.09); arm B, 1.0 (0.50‐1.84) and 0.3 (0.12‐0.85); arm C, 27.0 (13.29‐54.91) and 8.6 (3.15‐23.42). The most common adverse event, upper respiratory tract infection, was reported for 14 of 56 (25.0%; emicizumab) and 2 of 14 (14.3%; no prophylaxis) participants. No thrombotic events, thrombotic microangiopathies, or deaths were reported. Conclusion Emicizumab 1.5 mg/kg once weekly and 6 mg/kg every 4 weeks demonstrated bleed control in this study population, was well tolerated, and could improve use of prophylaxis in people with hemophilia A.