3107 Background: Protein arginine transferase 5 (PRMT5) overexpression plays an important role in pathogenesis of several cancers. LNP7457 is an investigational, orally active, highly potent, S-adenosylmethionine (SAM) competitive PRMT5 inhibitor with wider therapeutic window compared to other investigational PRMT5 inhibitors. Here, we report results of dose escalation (DE) and food-effect (FE) sub-studies of LNP7457 from a Phase 1 study in patients with advanced or metastatic solid tumors. Methods: This is first-in-human, multicenter, open-label study in patients with advanced or metastatic solid tumors with failed prior standard therapies or for whom no standard therapy exists. DE followed initial modified acceleration followed by 3+3 design. LNP7457 was administered orally in 21-day cycles [first 16 days (on-period) and last 5 days (off-period)] at escalating doses (1 to 4mg QD). Primary objective was to determine maximum tolerated dose (MTD) assessed by dose-limiting toxicities (DLT) in cycle 1; secondary objectives included safety, pharmacokinetics, pharmacodynamics and preliminary antitumor activity measured by RECIST v1.1. FE study was conducted as a single-dose cross over study at MTD to assess impact of food on PK of LNP7457. Results: 17 patients (9 male & 8 females) in DE received LNP745 at doses of 1mg (n = 1), 2mg (n = 8), 4mg (n = 2), 1.5mg (n = 6); median age 51.0 (range 23 - 76) years;Diagnosis included head and neck cancer (n = 9), cervix cancer (n = 2), breast cancer (n = 1), ovarian cancer (n = 1), pancreatic cancer (n = 1), gall bladder cancer (n = 1), prostate cancer (n = 1) and uterine cancer (n = 1). Sixteen patients discontinued treatment; progressive disease (n = 8); consent withdrawal (n = 4); AE (N = 2); death (n = 1) and lost to follow up (n = 1). One patient is ongoing at data cut-off of 31-Oct-2024. A total of 16 (94.1%) patients had at least 1 treatment emergent adverse event (TEAE). The majority of TEAEs were unrelated to LNP7457 (76.4%). Anemia (47.1%) and thrombocytopenia (23.5%) were the most common TEAEs. A total of 6 (35.3%) patients had serious TEAEs, thrombocytopenia (11.8%) being the most common serious TEAE. One patient in 4mg cohort had DLT of thrombocytopenia during cycle 1. None of the patients in 2mg cohort had DLT in cycle 1, hence 2 mg was determined as MTD. After single and multiple dosing in DE study, peak plasma concentrations of LNP7457 were observed between 2-4 hrs. A single-dose cross over FE study (n = 6) at 2mg dose showed no impact of food on PK of LNP7457. Target engagement based on reduction in plasma SDMA levels was observed at all dose levels in DE study. Preliminary efficacy in the form of stable disease was observed in 8 (66.7%) patients across 8 different tumor types. Conclusions: LNP7457 was well tolerated with desirable safety, PK/PD and preliminary efficacy profile. Clinical trial information: CTRI/2023/07/054753 .