Rain Therapeutics Plans Phase 2 Merkel Cell Carcinoma Clinical Trial (MANTRA-3) of Milademetan

Rain Therapeutics Inc. recently announced its plan to commence a Phase 2 clinical trial, named MANTRA-3, evaluating the efficacy of milademetan, an oral mouse double minute 2 (MDM2) inhibitor, as a monotherapy for the treatment of patients with Merkel cell carcinoma (MCC) refractory to immune checkpoint inhibition (ICI) in mid-2022.

“We are very excited about the recent preclinical data generated for milademetan in Merkel cell carcinoma, and believe the data warrant moving the program into a clinical study,” said Avanish Vellanki, Co-founder and Chief Executive Officer of Rain. “We hope to address the immense unmet medical need for patients after relapsing on first-line checkpoint inhibitors.”

Recent data presentations at the 2021 AACR-NCI-EORTC Virtual International Conference on Molecular Targets and Cancer Therapeutics demonstrated potent in vitro and in vivo activity of milademetan in several MCC models. Rain will prioritize its financial resources towards a Phase 2 clinical trial of milademetan in MCC and replace the previously planned Phase 2 clinical trial of milademetan in intimal sarcoma.

The MANTRA-3 trial is designed to evaluate the efficacy of milademetan as a monotherapy in patients with MCC that have progressed on immune checkpoint inhibitors. Approximately 30 patients are expected to be enrolled to receive milademetan. The primary endpoint of the trial is objective response rate (ORR) as measured by RECIST criteria. Secondary endpoints include duration of response, disease control rate, progression free survival by investigator assessment, growth modulation index, overall survival and safety.

Merkel cell carcinoma is a rare, aggressive type of skin cancer that frequently travels to other parts of the body. An aging population is driving increases in the number of new MCC cases and the incidence of MCC is predicted to reach >3,000 cases in 2025 in the US alone. Immune checkpoint inhibitors are the approved first line strategy for patients with relapsed or metastatic MCC, but many patients do not respond or stop responding to these therapies.

Milademetan is a small molecule, oral inhibitor of MDM2, which is oncogenic in numerous cancers. Milademetan has already demonstrated meaningful antitumor activity in an MDM2-amplified subtype of liposarcoma (LPS) and other solid tumors in a Phase 1 clinical trial, validating a rationally-designed dosing schedule to mitigate safety concerns and widen the therapeutic window of MDM2 inhibition. Milademetan is being evaluated in an ongoing Phase 3 clinical trial in patients with LPS (MANTRA) with a planned Phase 2 tumor-agnostic basket trial in certain solid tumors (MANTRA-2) anticipated to start in the fourth quarter of 2021. Rain Therapeutics also anticipates commencing a Phase 2 clinical trial of milademetan (MANTRA-3), for the treatment of patients with Merkel cell carcinoma refractory to immune checkpoint inhibition (ICI), in mid-2022. Milademetan has received US FDA Orphan Drug Designation for patients with LPS.

Rain Therapeutics Inc. is a late-stage precision oncology company developing therapies that target oncogenic drivers for which it is able to genetically select patients it believes will most likely benefit. This approach includes using a tumor-agnostic strategy to select patients based on their tumors’ underlying genetics rather than histology. Rain’s lead product candidate, milademetan, is a small molecule, oral inhibitor of MDM2, which is oncogenic in numerous cancers. In addition to milademetan, Rain is also developing a preclinical program that is focused on inducing synthetic lethality in cancer cells by inhibiting RAD52.