Background: APG-1387 is a bivalent small molecule Smac mimetic that antagonizes the IAPs. Preclinical studies have shown its dose- and schedule-dependent, strong antitumor activities in multiple human cancer xenograft models. In addition, the preclinical results strongly support the notion that APG-1387 in combination with anti-PD1 antibody would be a very attractive approach for cancer therapy. Methods: Phase I dose-escalation study enrolled 28 patients with advanced solid tumors in China (#CTR20150161). During dose escalation, the patients received APG-1387 (0.3–45 mg) intravenous infusion for 30 minutes once every week for 3 out of 4 weeks in a 28-day cycle until disease progression. Endpoints included safety (primary), pharmacokinetics (PK), pharmacodynamics (PD), and antitumor activity assessed every 8 weeks per RECIST v1.1. Results: Till Jan 15, 2018, 28 patients had been treated in 8 cohorts of APG-1387(0.3mg, 0.6mg, 4mg, 7mg, 12mg, 20mg, 30mg, 45mg). Twenty-eight patients received at least 1 cycle of treatment. The MTD was not reached yet. No DLT was observed during Cycle 1 across dose levels. Twenty-five of 28 patients experienced at least 1 TEAE. The most common TEAEs were vomiting, abdominal pain, anemia, cough, headache, AST increased and ventricular arrhythmia. Of these, 4 grade 3/4 clinical TEAEs including blood bilirubin increased, ALT increased, hypokalemia , pain and soft tissue infection were documented across dose levels. A total of 12 definitively or possibly drug-related AE occurred to date. Human PK data of APG-1387 showed a dose proportionality in exposure, elimination appeared to be linear, no significant accumulation was observed in plasma. Preliminary results from the Human Cytokine 30-Ple analyses indicated that IL-12, IP-10 and MCP-1 were significantly increased in the patient plasma after treatment with APG-1387, indicating potential effects of APG-1387 on the host immune responses. Conclusions: APG-1387 was well tolerated and had manageable adverse events.Further evaluation of APG-1387 in combination with immunotherapy agents in patients with advanced solid tumors or hematologic malignancies is recruiting. Clinical trial information: NCT03386526. Clinical trial information: 20150161.