In the quest for improved treatments for advanced dedifferentiated liposarcoma, characterized by MDM2 gene amplification, there is a need for novel therapeutic approaches. Milademetan, a potent and selective small molecule inhibitor, targets the MDM2-p53 interaction, thereby reactivating p53 and inducing apoptosis in malignant cells with wild-type TP53. The MANTRA study (RAIN-3201; NCT04979442) is a Phase III trial comparing milademetan with trabectedin in patients with previously treated unresectable/metastatic dedifferentiated liposarcoma. According to the data presented at the ESMO ASIA 2023, the median PFS for milademetan was 3.6 months, as opposed to 2.2 months for trabectedin. With a median follow-up of 7.1 months, the overall survival for Milademetan was 9.4 months, and for trabectedin, it was 10.2 months. Based on the blinded independent central review (BICR), the ORR reported for milademetan and trabectedin was 4.7% and 3.4% respectively. Overall, there was no significant difference in median PFS (BICR) between milademetan and trabectedin. In terms of safety analysis, the most common treatment-emergent adverse events (TEAEs) occurred in ≥20% of patients, and no new safety signals were detected for milademetan. Moreover, the discontinuation associated with AEs was more common with trabectedin versus milademetan.

 Conclusion

Comparable median progression-free survival (PFS) observed between milademetan and trabectedin suggests no significant distinction based on the BICR assessment. Milademetan maintains a consistent safety profile with no new signals identified. Future efforts should focus on discerning the patient population most likely to derive benefits from milademetan.

Reference reports by DelveInsight for more in-depth analysis and key coverage - 

• Liposarcoma Market Insight, Epidemiology, And Market Forecast
• Liposarcoma Pipeline Insight