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298 Background: The treatment landscape for pts with uHCC has recently expanded. However, there is an unmet need for effective treatment options in CPB pts. LEN is approved first-line in uHCC based on the REFLECT study (Child-Pugh A [CPA] pts were allowed, per inclusion criteria). In a prior analysis of REFLECT, pts treated with LEN benefited irrespective of baseline liver function (ALBI grade 1 or 2; Child-Pugh score 5 or 6). To determine outcomes in pts with reduced liver function, we report a post hoc analysis of key efficacy and safety results in LEN-treated pts from REFLECT who progressed to CPB and those who did not within the first 8 weeks of treatment. Methods: In REFLECT, pts with uHCC were randomized 1:1 to LEN (per bodyweight: 12 mg/day for ≥60 kg; 8 mg/day for < 60 kg) or sorafenib (400 mg twice daily) in 28-day cycles. This analysis assessed ORR. Landmark analyses (starting at week 8) of PFS, time-to-progression (TTP), and OS in CPB pts and in pts who remained CPA at 8 weeks post-randomization were also conducted. Tumors were assessed by mRECIST by independent imaging review. Safety was also assessed from baseline. Results: This subgroup analysis included LEN-treated pts (n = 60) who progressed to CPB within the first 8 weeks of treatment (CPB pts) and 413 pts who did not (CPA pts). At baseline, 26.7% and 73.1% of pts had an ALBI grade of 1 and 73.3% and 26.9% of pts had an ALBI grade of 2 in CPB and CPA pts, respectively. ORR was 28.3% (95% CI 16.9–39.7) for CPB pts and 42.9% (95% CI 38.1–47.6) for CPA pts. A landmark analysis showed a median PFS of 3.7 mos (95% CI 1.8–7.4) for CPB pts and 6.5 mos (95% CI 5.6–7.4) for CPA pts from the week 8 timepoint. Landmark analyses at week 8 also showed that the median TTP was 5.6 mos (95% CI 3.5–9.3) for CPB pts and 7.3 mos (95% CI 5.6–7.4) for CPA pts; the median OS was 6.8 mos (95% CI 2.6–10.3) for CPB pts and 13.3 mos (95% CI 11.6–16.1) for CPA pts per week 8 landmark analyses. As expected, efficacy appeared to be greater in CPA pts versus CPB pts; however, OS of 6.8 months in CPB pts after the week 8 landmark is notable. Moreover, median duration of treatment was 3.2 mos for CPB pts and 6.9 mos for CPA pts, thereby suggesting CPB pts can remain on LEN. The incidence of grade ≥3 treatment-related AEs (TRAEs) was 71.7% in CPB pts and 54.7% in CPA pts. TRAEs leading to discontinuation occurred in 18.3% of CPB pts and 7.5% of CPA pts. Conclusions: In this post hoc analysis of pts in REFLECT, we examine the key efficacy and safety results for LEN-treated pts who progressed to CPB by week 8. This post hoc analysis is limited by its descriptive nature; however, the results indicate that further study of LEN in CPB pts with uHCC is warranted. Clinical trial information: NCT01761266.