Background: First-line atezolizumab (atezo) + bevacizumab (bev) has been approved in > 80 countries based on significantly longer survival vs sorafenib (sor) in systemic treatment (tx)–naive patients (pts) with unresectable HCC in IMbrave150 (NCT03434379; Finn NEJM 2020). This clinically meaningful tx benefit was maintained with an additional 12 months of follow-up (Finn ASCO GI 2021). We report the efficacy and safety in pts who received atezo beyond radiological progression until loss of clinical benefit. Methods: Pts were randomized 2:1 to receive atezo 1,200 mg IV + bev 15 mg/kg IV q3w or sor 400 mg bid until unacceptable toxicity or loss of clinical benefit per investigator (INV). In the presence of clinical benefit, pts with progressive disease (PD) per INV RECIST 1.1 (not at a critical anatomical site) could continue study tx. Pts from the atezo + bev arm who had PD and continued atezo were included. Results: Of the 336 pts who received atezo + bev, 236 had PD, of whom 130 continued atezo (± bev), 60 had other tx, and 46 received no tx on or after first PD. Of the pts who continued atezo, 78% were Barcelona Clinic Liver Cancer (BCLC) stage C and 80% Child-Pugh A5 vs pts receiving other tx (85% BCLC stage C, 72% Child-Pugh A5). Sor (13% and 53%) and lenvatinib (14% and 35%) were the most common other txs received post PD among pts who continued atezo or received other tx, respectively. At clinical cutoff (August 31, 2020), the median number of cycles of atezo received post PD was 5 (range, 1-33) and 41 (32%) pts received ≥ 10 cycles. 60 of 130 (46%) pts who continued atezo died vs 180 of 336 (54%) receiving atezo + bev in the ITT population. See Table for efficacy data from baseline (BL) and PD. Grade (Gr) 3/4 and tx-related Gr 3/4 AEs occurred in 30 (23%) and 21 (16%) pts who continued atezo, respectively. There were 6 (5%) Gr 5 AEs, none tx-related. Conclusions: Atezo + bev is the standard of care for pts with unresectable HCC. In IMbrave150, pts with maintained clinical benefit continuing atezo after PD may have further benefited from staying on tx, although interpretation is limited by selection bias (prespecified criteria excluding pts with loss of clinical benefit). These data suggest that tx with atezo until loss of clinical benefit may contribute to post-PD outcomes. Beyond this exploratory analysis in select pts, the value of tx with atezo beyond formal progression will be assessed prospectively in IMbrave251 (NCT04770896). Clinical trial information: NCT03434379.