e15162 Background: SOS1 (Son of Sevenless1) is a critical regulator of RAS signaling, facilitating RAS activation to drive cell proliferation and survival. Dysregulated SOS1 activity contributes to oncogenic signaling and tumor progression. LNP8701 is an orally active, investigational SOS1 inhibitor designed to block SOS1-mediated RAS activation, thereby limiting oncogenic signaling that promotes tumor growth. Here, we present results from the dose-escalation (DE) sub-study from a Phase 1 study of LNP8701 in patients with metastatic solid tumors. Methods: This is a first-in-human, multicenter, open-label study in patients with 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 based on DSMB recommendation. LNP8701 was administered orally once daily for 6 cycles of 28 days each. Primary objective was to determine maximum tolerated dose (MTD) assessed by dose-limiting toxicities (DLT) in cycle 1; secondary objectives included safety, pharmacokinetics and preliminary antitumor activity measured by RECIST v1.1. Results: 20 patients (10 males & 10 females) of stage IV cancer including 5 patients of cervical cancer, 3 patients each of kidney and lung cancer, 2 patients of rectal cancer and 1 patient each of vaginal vault, colon, colorectal, pancreatic, ovarian, breast cancer and left thigh sarcoma were enrolled in DE study. Patients received LNP8701 at doses of 100 mg (n = 1), 200 mg (n = 7), 300 mg (n = 7), 400 mg (n = 5). Median age was 50.5 (range 29 - 70) years. A total of 16 (80%) patients had at least 1 treatment emergent adverse event (TEAE). The majority (80%) of TEAEs were unrelated to LNP8701. The most common TEAEs were anemia (40%), vomiting (25%), and pain in extremity (25%). A total of 6 (30%) patients had serious TEAEs. One patient in 200 mg cohort had a DLT of Grade 4 thrombocytopenia during cycle 1. None of the patients in 100 mg, 300 mg and 400 mg cohort had DLT in cycle 1. Fifteen patients discontinued treatment due to progressive disease (n = 14) and SAE (n = 1) as of data cut-off date 21-Jan-2025. Three patients continued LNP8701 beyond 6 cycles on compassionate basis, of which 2 patients (1 patient each of Ca vaginal vault and Ca breast) completed 12 cycles with stable disease and 1 patient with Ca cervix completed 14 cycles with stable disease. The patient with Ca vaginal vault had partial response at the end of cycle 4 and cycle 6. Overall, 5 (25%) patients had stable disease and 1 (5%) patient had partial response as the best overall response during the study. After single and multiple dosing, peak plasma concentrations of LNP8701 were observed between 30 mins to 1 hr. Conclusions: LNP8701 was well tolerated with desirable safety, PK and preliminary efficacy profile. Clinical trial information: CTRI/2024/08/072373.