Background: In prior studies, the efficacy and safety of selpercatinib, a selective RET inhibitor, was consistent in RET+ NSCLC pts across geographies. As previously reported, LIBRETTO-431 met its primary endpoint of improved PFS by blinded independent central review (BICR) at the pre-planned interim analysis. Here we report the efficacy and safety from LIBRETTO-431 in pts from East Asia, a majority of the study population. Methods: LIBRETTO-431 (NCT04194944) is a randomized, open-label phase 3 trial comparing 1L selpercatinib vs control (platinum/pemetrexed +/- pembrolizumab). Geography (East Asia vs non-East Asia) was a stratification factor. BICR-assessed PFS, ORR and DOR were examined in pts from East Asia randomized with investigator’s intent to treat with pembrolizumab (ITT-pembro) if assigned to control. AE data were collected for all pts from East Asia who received at least one dose of selpercatinib or control (n=140). Results: Of 142 randomized pts from East Asia, 116 were included in the ITT-pembro population (selpercatinib: n=75, control: n=41). Baseline characteristics were well balanced, however the selpercatinib arm had slightly more pts from East Asia vs the control arm (58% vs 49%). In ITT-pembro pts from East Asia, with a median follow up of 19.4 mo and 21.2 mo in the selpercatinib and control arms respectively, the median PFS was not yet reached with selpercatinib (95% CI: 16.4-NE) vs 11.1 mo (95% CI: 7.0-16.8) with control. At 12 mo the PFS rate was 72.8% with selpercatinib vs. 41.7% with control. The ORR was 86.7% (95% CI: 76.8-93.4) with selpercatinib vs 61.0% (95% CI: 44.5-75.8) with control. Similar results were observed in pts from East Asia in the overall ITT population. The most common AEs reported in pts from East Asia on selpercatinib included elevated AST (73.6%), elevated ALT (70.3%), hypertension (60.4%), increased blood bilirubin (52.7%) and diarrhea (44.0%) while those reported with control included anemia (61.2%), elevated AST (49.0%), leukopenia (49.0%), neutropenia (44.9%) and elevated ALT (42.9%). A summary of safety data for selpercatinib vs control in pts from East Asia is presented in the table. Conclusions: LIBRETTO-431 is the first randomized study to report efficacy and safety of a RET inhibitor in pts from East Asia. Consistent with the results in the overall population, selpercatinib demonstrated superior PFS compared to chemotherapy + pembrolizumab in 1L pts from East Asia. These data support early comprehensive genomic testing and the use of selpercatinib as the preferred 1L regimen in RET+ NSCLC pts across geographies. Clinical trial information: NCT04194944.