On October 26, 2020 Rain Therapeutics Inc., a privately-held, clinical stage biotechnology company focused on targeted therapies for patients with cancer, reported an update on data from the Phase 1 clinical trial of RAIN-32 (milademetan), an oral MDM2 inhibitor, during a late-breaker oral presentation at the 32nd EORTC-NCI-AACR (Free EORTC-NCI-AACR Whitepaper) Virtual Symposium on October 25, 2020 (Press release, Rain Therapeutics, OCT 26, 2020, View Source [SID1234569045]).
Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:
Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing
Schedule Your 30 min Free Demo!
The presentation highlighted the enhanced safety profile of RAIN-32, enabled by its unique drug-like properties, when administered on an intermittent dosing schedule as well as prolonged progression-free survival in patients with well-differentiated/de-differentiated (WD/DD) liposarcoma (LPS).
"We are pleased to highlight these positive data," said Avanish Vellanki, co-founder and chief executive officer of Rain. "These analyses of the Phase 1 study demonstrate the opportunity for RAIN-32 to provide safe and effective MDM2 inhibition. We look forward to further evaluating RAIN-32 both in liposarcoma, as well as in other solid tumor indications characterized by MDM2 gene amplification with this dosing regimen."
The Phase 1 dose escalation and expansion study evaluated RAIN-32 across four dose schedules in patients (n=107) with liposarcoma, solid tumors or lymphomas. Key findings from the oral presentation include:
An intermittent dose schedule of QD 3/14 x 2 of a 28-day cycle (Schedule D) allowed the highest MTD for RAIN-32 (260 mg) versus the more continuous dose schedules (Schedules A, B and C)
RAIN-32 dosed on Schedule D at 260 mg exhibited an improved safety profile versus the more continuous dosing schedules:
Incidence of all ≥ Gr 3 TEAEs in the 260 mg Schedule D cohort (n=20) fell to 20% versus 55% in the Schedules A, B, and C cohorts (n=78)
Incidence of ≥ Gr 3 thrombocytopenia, neutropenia and anemia, representing the predominant dose-limiting toxicities of MDM2 inhibition, fell to 15%, 5% and 0% in Schedule D from 35%, 18% and 10% in the other schedules, respectively
No Gr 4/5 toxicities were observed at 260 mg dose in Schedule D
The Schedule D regimen also conferred numerically improved progression-free survival as compared to the continuous dose schedules
In 17 patients evaluable for efficacy receiving Schedule D at doses ≤ 260 mg, median progression-free survival was 8.0 months
The 260 mg Schedule D regimen has been identified as the dose and schedule for further studies
Tumor shrinkage and objective responses were also observed in selected non-liposarcoma patients with MDM2 gene amplification, indicating potential for future agnostic clinical trials using biomarker selection
Rain intends to initiate subsequent clinical studies of RAIN-32 in liposarcoma and other tumors in the second half of 2021.
About RAIN-32
RAIN-32 has been evaluated in patients with various solid tumors, acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) and has received Orphan Drug Designation for the treatment of liposarcoma. RAIN-32 also has been evaluated in continuous and intermittent dose schedules that may offer a differentiated tolerability profile as compared to other MDM2 programs.
A separate clinical study for RAIN-32 is ongoing to evaluate safety and efficacy in patients with FLT3-ITD AML in combination with the FLT3 inhibitor, quizartinib. In addition, multiple investigator-sponsored studies are being conducted by MD Anderson Cancer Center (MDACC) as well as National Cancer Center Hospital (NCCH) in Tokyo, Japan.