The MDM2-p53 antagonist BI 907828 in patients with advanced or metastatic solid tumors: results of a phase Ia, first-in-human, dose-escalation study.

BI 907828 is an oral MDM2-p53 antagonist that has shown encouraging antitumor activity in vivo. We present phase Ia results from an open-label, first-in-human, phase Ia/Ib study investigating BI 907828 in patients with advanced solid tumors (NCT03449381). Fifty-four patients received escalating doses of BI 907828 on day 1 of 21-day cycles (D1q3w) or days 1 and 8 of 28-day cycles (D1D8q4w). Based on dose-limiting toxicities during Cycle 1, the MTD was selected as 60 mg for D1q3w and 45 mg for D1D8q4w. The most common treatment-related AEs (TRAEs) were nausea (74.1%) and vomiting (51.9%); the most-common grade ≥3 TRAEs were thrombocytopenia (25.9%) and neutropenia (24.1%). As evidence of target engagement, time- and dose-dependent increases in GDF-15 levels were seen. Preliminary efficacy was encouraging (11.1% overall response and 74.1% disease control rates), particularly in well-differentiated or dedifferentiated liposarcoma patients (100% and 75% disease control rates, respectively).