Rain Oncology’s Milademetan Fails in Phase 3 Trial in Dedifferentiated Liposarcoma

Rare Daily Staff

Rain Oncology said its lead product candidate milademetan failed to achieve its primary endpoint of progression free survival in a phase 3 study in patients with the rare cancer dedifferentiated liposarcoma.

Milademetan (also known as RAIN-32) is an oral small molecule inhibitor of the MDM2-p53 complex that reactivates p53. Milademetan has demonstrated antitumor activity in an MDM2-amplified subtype of liposarcoma (LPS) and other solid tumors in a phase 1 clinical trial, supported by a rationally designed dosing schedule to mitigate safety concerns and widen the potential therapeutic window of inhibition of the MDM2-p53 complex.

Rain is evaluating milademetan in a phase 2 tumor-agnostic basket trial in certain solid tumors with MDM2 amplification (MANTRA-2). Rain anticipates commencing a phase 1/2 clinical trial to evaluate the safety, tolerability and efficacy of milademetan in combination with Roche’s atezolizumab in patients with loss of cyclin-dependent kinase inhibitor 2A (CDKN2A) and wildtype p53 advanced solid tumors (MANTRA-4), in mid-2023.

Milademetan has received Orphan Drug designation from the U.S. Food and Drug Administration for the treatment of LPS.

The study found that the median PFS for milademetan was 3.6 months vs 2.2 months for trabectedin. The most common treatment emergent adverse events (TEAEs) in the milademetan arm included nausea, thrombocytopenia, anemia, vomiting, and neutropenia. The most common grade 3/4 TEAEs were thrombocytopenia (39.5 percent), neutropenia (25.5 percent) and anemia (18.6 percent).

Dose reductions in the milademetan arm were 44.2 percent vs 29.1 percent in the trabectedin arm. Discontinuation in the milademetan arm due to AEs were 11.6 percent vs 19.0 percent for trabectedin. Based upon these topline data, Rain does not expect to pursue further development of milademetan in DD LPS. Rain hopes to present the MANTRA data in an upcoming medical conference.

“We are very disappointed in the outcome of the MANTRA trial, as the results did not closely mirror prior clinical results in patients with DD LPS,” said Avanish Vellanki, co-founder and CEO of Rain. “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. Rain’s mission remains to advance science, and therefore we will further evaluate the totality of the MANTRA data to support the scientific and medical community in the hope we can aid others in finding new strategies for patients with DD LPS.

Based on the MANTRA topline results, he said Rain will also re-evaluate the path forward for milademetan.

Photo: Avanish Vellanki, co-founder and CEO of Rain Oncology