Phase 3 trial of milademetan in dedifferentiated liposarcoma fails to meet primary endpoint
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Milademetan failed to significantly extend PFS among patients with dedifferentiated liposarcoma, according to topline data released by the agent’s manufacturer.
Milademetan (Rain Oncology) is an oral, small-molecule murine double minute-2 (MDM2) inhibitor that reactivates p53.
The randomized, open-label MANTRA trial evaluated the efficacy, safety and tolerability of the agent vs. standard-of-care trabectedin (Yondelis; Janssen, PharmaMar) among 175 patients with unresectable or metastatic dedifferentiated liposarcoma.
PFS by blinded independent central review served as the primary endpoint. Secondary endpoints included OS, PFS by investigator assessment, objective response rate, duration of response, disease control rate, safety and patient-reported outcomes.
Researchers reported median PFS of 3.6 months with milademetan vs. 2.2 months with trabectedin (HR = 0.89; 95% CI, 0.61-1.29) based on 115 total events.
“We are very disappointed in the outcome of the MANTRA trial, as the results did not closely mirror prior clinical results in patients with [dedifferentiated liposarcoma],” Avanish Vellanki, co-founder and CEO of Rain Oncology, said in a press release. “We are truly saddened we will not likely be able to offer patients new treatment options for this challenging disease. However, the quality and robustness of the global MANTRA trial reflects an unambiguous data set.”
The most common treatment-emergent adverse events in the milademetan group included nausea, thrombocytopenia, anemia, vomiting and neutropenia. The most common grade 3/ to grade 4 treatment-emergent adverse events included thrombocytopenia (39.5%), neutropenia (25.5%) and anemia (18.6%).
Dose reductions occurred among 44.2% of patients in the milletmeal group and 29.1% of patients in the trabectedin group, with the milademetan group exhibiting lower rates of discontinuation due to adverse events (11.6% vs. 19%) and treatment-emergent serious adverse events (36% vs. 48.1%).
Rain Oncology does not plan to pursue further development of milademetan for patients with dedifferentiated liposarcoma. Data may be presented at a future medical conference.
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