AMG 193 Effective in Multiple Tumor Types

Area of Science:

• Oncology
• Molecular Biology
• Pharmacology

Background:

• Methylthioadenosine (MTA) overproduction is common in cancers with methylthioadenosine phosphorylase (MTAP) gene deletions.
• PRMT5 is a key enzyme in the arginine methylation pathway, and its inhibition is a therapeutic strategy for MTAP-deleted tumors.
• Targeting PRMT5 aims to disrupt cancer cell growth and survival.

Purpose of the Study:

• To evaluate the safety and preliminary efficacy of AMG 193, a novel MTA-cooperative PRMT5 inhibitor.
• To assess the response rate in patients with advanced MTAP-deleted solid tumors treated with AMG 193.
• To identify tumor types that may benefit from PRMT5 inhibition.

Main Methods:

• Phase I clinical trial design.
• Treatment with AMG 193 in patients with advanced MTAP-deleted solid tumors.
• Tumor response assessment using imaging scans post-treatment.

Main Results:

• Partial responses were observed in 5 out of 39 patients (approximately 12.8%) with advanced MTAP-deleted solid tumors.
• Responses were noted across diverse tumor types, including esophageal, pancreatic, renal cell, gallbladder, and ovarian Sertoli-Leydig cell cancers.
• Preliminary data suggest a potential therapeutic window for PRMT5 inhibition in specific cancer contexts.

Conclusions:

• AMG 193 demonstrates preliminary anti-tumor activity in patients with MTAP-deleted solid tumors.
• The observed responses across multiple tumor types warrant further investigation.
• PRMT5 inhibition represents a promising targeted therapy approach for cancers with MTAP deletions.