3125 Background: APG-1387 is a novel, bivalent small molecule IAP (inhibitor of apoptosis proteins) inhibitor. It has shown strong antitumor activities in multiple human xenograft cancer models. APG-1387 also acts as host immune modulator, supporting the notion that APG-1387 in combination with anti-PD1 antibody for cancer therapy. Methods: This study consists of two parts (NCT03386526). Part 1 is the dose escalation study of APG-1387 including a mPC (metastatic pancreatic cancer) cohort expansion. Part 2 is the dose escalation and cohort expansion study of APG-1387 in combination with pembrolizumab. APG-1387 is administrated IV for 30 minutes once weekly in a 21-day-cycle. Pembrolizumab is administrated at 200mg IV on day1 of a 21-day-cycle. The study objectives are to assess the safety, pharmacokinetics (PK), pharmacodynamics (PD), and efficacy (assessed per RECIST v1.1 every 6 weeks). Results: Through Jan 4, 2019, total 23 patients had been treated in 4 cohorts of APG-1387 (20mg, 30mg, 45mg, 60mg). Two DLTs were observed at 60mg including lipase increase and Bell’s palsy, MTD was determined as 45mg. Nineteen of 23 patients experienced at least 1 TEAE. The most common TEAEs were nausea (21.7%), fatigue (17.4%), decreased appetite (13.0%), and abdominal pain (13.0%). Three grade 3 TEAEs including elevated bilirubin, lipase increase, and shortness of breath were documented at 45mg and 60mg. Three out of six mPC patients (one at 60mg, two at 45mg) achieved SD, one of them at 45mg has been treated > 5 cycles with confirmed SD (-18%). Two patients, who were treated with APG-1387 at 20mg in combination with pembrolizumab, had no DLT observed during the first cycle. Preliminary PK data of APG-1387 showed a dose proportionality in exposure (Cmax and AUC) over the dose range of 20-60 mg. Conclusions: APG-1387 was well tolerated and had manageable adverse events. The potential effects of APG-1387 alone or in combination with pembrolizumab deserve further exploration in patients with advanced solid tumors, especially in the mPC patients. Clinical trial information: NCT03386526.