ASCO20: Targeting MDM2 in Merkel Cell Carcinoma
Posted: Thursday, June 4, 2020
KRT-232, a first-in-class murine double minute 2 (MDM2) inhibitor, has shown activity in patients with p53 wild-type Merkel cell carcinoma who have relapsed on or are refractory to anti–PD-1/L1 agents. Oncoproteins from the Merkel cell polyomavirus may inhibit p53 tumor suppressor functions through indirect activation of MDM2. Michael K.K. Wong, MD, PhD, of The University of Texas MD Anderson Cancer Center, Houston, and colleagues presented this phase 2 poster as a part of the ASCO20 Virtual Scientific Program (Abstract 10072).
This open-label, multicenter trial treated patients initially with 240 mg of KT-232 once a day on days 1 to 7 of a 21-day cycle. This cohort was closed due to grade 3 and 4 cytopenias; patients were instead moved to 240 mg of KT-232 once a day for days 1 to 5 of a 28-day cycle to allow for hematologic recovery. There was an additional cohort of patients treated with 180 mg of KT-232 on days 1 to 5 of a 28-day cycle.
At the time of data analysis, six patients had been treated on the 240-mg 7-day schedule, three patients were treated on the 240-mg 5-day schedule, and two patients were treated on the 180-mg 5-day cycle. The median time on the study was 11.3 weeks. Two patients achieved a partial response and one patient had stable disease at week 6. By week 12, two partial responses were reported. The objective response rate for the nine evaluable patients was 33%.
All patients reported treatment-related adverse events, including six with grade 3 or 4 toxicity. The most common adverse events included neutropenia, anemia, leukopenia, thrombocytopenia, diarrhea, nausea, fatigue, lymphopenia, hypomagnesemia, lipase level increase, and sinus tachycardia. One patient experienced a grade 5 adverse event of respiratory failure/ascites, which was associated with disease progression.
Disclosures: For full author disclosures, visit coi.asco.org.
