Supplementary Figure 1 from 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

LoRusso, Patricia; Yamamoto, Noboru; Patel, Manish R.; Laurie, Scott A.; Bauer, Todd M.; Geng, Junxian; Davenport, Teffany; Teufel, Michael; Li, Jian; Lahmar, Mehdi; Gounder, Mrinal M.

doi:10.1158/2159-8290.27025628.v1

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Supplementary Figure 1 from 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

journal contribution

posted on 2024-09-16, 09:33 authored by Patricia LoRusso, Noboru Yamamoto, Manish R. Patel, Scott A. Laurie, Todd M. Bauer, Junxian Geng, Teffany Davenport, Michael Teufel, Jian Li, Mehdi Lahmar, Mrinal M. Gounder

GDF-15 fold change from baseline for dose-escalation cohorts receiving BI 907828 D1q3w and BI 907828 D1D8q4w

History

ARTICLE ABSTRACT

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).