Rain liposarcoma drug disappoints in phase 3 trial

May 22, 2023

California-based precision medicine developer Rain Oncology announced that its lead candidate failed to best standard of care chemotherapy in a phase 3 liposarcoma trial.

Milademetan is an oral, small molecule inhibitor of the MDM2-p53 complex that reactivates p53. Rain was studying the treatment  in patients with dedifferentiated liposarcoma, which is one of the five subtypes of liposarcoma — a malignancy of fat cells. Dedifferentiated liposarcoma (DDLPS) occurs when a low grade tumor changes and newer cells with higher grade arise in the tumor.

According to Rain, the phase 3 MANTRA trial did not meet its primary endpoint of progression free survival (PFS) by blinded independent central review compared to the standard of care chemotherapy — Janssen Pharmaceuticals’ Yondelis (trabectedin). The median PFS for milademetan was 3.6 months vs. 2.2 months for trabectedin.

Rain, which was founded in 2017, added milademetan to its pipeline of targeted cancer therapies in a 2020 deal with Daiichi Sankyo. At the time, Rain was banking that the treatment, with a differentiated tolerability profile, would enable longer-term therapy as compared to other MDM2 programs in development. 

Now, based on the recent topline data, Rain says it does not expect to pursue further development of milademetan in the DDLPS indication. The news sent the company's share plummeting by over 80%.