A phase I study of a novel MDM2 antagonist APG-115 in patients with advanced solid tumors.

• DOI: 10.1200/jco.2019.37.15_suppl.3126
• Publication Date: 2019-05-27T15:59:51Z
• Authors: Drew W. Rasco; Nehal J. Lakhani; Yufeng Li; Lichuang Men; Hengbang Wang; Jiao Ji; Yuefen Tang; Zhiyan Liang; Alex Amaya; Kathy Estkowski; Joan Sun; Yingjie Huang; Dajun Yang; Yifan Zhai
• Keywords: Pharmacodynamics; White blood cell

3126 Background: APG-115 is a potent and orally active small-molecule MDM2 protein inhibitor. Binding to protein, restores p53 tumor suppressive function via induction of apoptosis in cells retaining wild-type p53. In addition, enhanced antitumor activity was demonstrated the syngeneic models after combined with PD-1 blockade. Methods: This Phase I study (APG-115-US-001) designed enroll patients advanced solid tumors US (NCT02935907). Study objectives included assess safety, dose limited toxicity (DLT), pharmacokinetics (PK), pharmacodynamics (PD), (assessed every 8 weeks per RECIST v1.1). The received other day (QOD) at designated (ranging from 10 300 mg) for first 21 days 28-day cycle, until disease progression. Results: Up Jan 4 2019, total 28 were treated various doses (one patient 10mg, 20mg 50mg, respectively; 14 100mg, 6 200mg, 5 300mg). median number prior systemic anticancer therapies (range 0-15). DLTs observed during cycle 1, including one grade 2 thrombocytopenia 3 300mg, fatigue 100mg 300mg respectively. most common AEs (reported ≥10% pts) included: fatigue, nausea, vomiting, diarrhea, decreased appetite, dehydration, neutrophil count decreased, white blood cell pain extremity, thrombocytopenia. Grade or treatment related (10.7%), (10.7%). Six had stable (SD) two treatments, them are continuing this study. PK analyses indicated that exposure (Cmax AUC) generally increases increase level 20 mg mg. Conclusions: well tolerated manageable adverse events. MTD/RP2D monotherapy oral administration, QOD determined as 100 Further evaluation combination pembrolizumab ongoing. Clinical trial information: NCT02935907.