Abstract Background: PD-L1 expression is associated with reduced survival and an unfavorable prognosis in a wide range of cancers. LY3300054 (LY) is a PD-L1 inhibitor that blocks the interaction between PD-L1 and its receptors. The added benefit of combining a second therapeutic agent is an area of active interest. This study (NCT02791334) will assess the safety, tolerability and efficacy of LY as monotherapy and in combination with ramucirumab (R), abemaciclib (A) and merestinib (M). Here we report phase 1a safety and preliminary efficacy results from completed LY, LY+R and LY+M cohorts. Methods: This ongoing, phase 1a/b, multi-center, dose escalation and expansion study enrolled pts with histologically or cytologically confirmed advanced solid tumor having ECOG PS 0-1 and with measurable disease. Primary objective for Phase 1a was to assess safety and tolerability. Secondary objectives include assessment of pharmacokinetics, efficacy and biomarkers (exploratory). Pts received intravenous infusions of LY: Q2W at 70, 200, 700 mg; Q3W at 1000 mg; Q4W at 1800 mg; LY+R: LY (Q2W 200, 700 mg; Q3W 1400 mg) + R (Q2W, Q3W 8 mg/kg); LY+M: LY (Q2W 200, 700 mg) + M (QD 120 mg oral). Adverse events (AEs) were assessed per NCI CTCAE v4.0. Tumor assessments were performed using RECIST v1.1. Results: As of 4 September 2017, 38 pts ([LY: Q2W, n=10; Q3W, n=3; Q4W, n=3]; LY+R [(Q2W, n=7; Q3W, n=3)]; LY+M Q2W, n=12) were treated. No DLTs were observed and there were no deaths due to AEs while on treatment. Pts with Gr3 treatment-related AEs (TRAEs) were: LY Q3W (n=1) with nausea, vomiting and fatigue; LY+R Q2W (n=2) with decreased appetite, pulmonary embolism and hypertension; Q3W (n=1) with lipase and amylase increase; no Gr 4/5 TRAEs were reported. Serious adverse events possibly related to study treatment were LY Q3W (n=1) Gr3 nausea and vomiting, and LY+R (n=1) Gr3 pulmonary embolism. There were no TRAEs leading to discontinuation of study treatment. The pharmacokinetics of LY was linear in the dose range tested, with a half-life of approximately 3 weeks, which did not appear to be affected by concomitant doses of M or R. Tumor tissue and blood were collected for biomarker analysis, including but not limited to, PD-L1 and CD8 expression by IHC and whole blood immunophenotyping; preliminary biomarker data will be presented. Preliminary efficacy data showed confirmed partial response in LY +R Q2W: 1pt (esophageal cancer), LY +M Q2W: 1pt (pancreatic cancer) and stable disease in LY Q2W: 3pts, LY+R: Q2W 4pts, Q3W 2pts as their best response. As of the data cut-off, 11 pts (29%) remain on treatment. Conclusions: LY alone or in combination with R or M appears to be well tolerated and demonstrated preliminary antitumor activity in pts with advanced solid tumors. The PK characteristics of LY support Q2W, Q3W, and possibly the Q4W dosing regimens. Citation Format: Amita Patnaik, Yung-Jue Bang, Hyun C. Chung, María José de Miguel Luken, Timothy A. Yap, Leijun Hu, Anna M. Szpurka, Danni Yu, Anindya Chatterjee, Shivani Nanda, Burkhard Vangerow, Mythili Koneru, Johanna Bendell. Interim safety and clinical activity in patients (pts) with advanced refractory solid tumors from a phase Ia/b study investigating the novel anti-PD-L1 antibody (LY3300054) administered alone or in combination with other agents [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr CT018.