2022 World Conference on Lung Cancer (ePosters)-EP08.02-116. Design of a Phase 1 Study of AMG 193, an MTA-Cooperative PRMT5 Inhibitor, in Patients with Advanced MTAP-Null Solid Tumors

EP08.02-116. Design of a Phase 1 Study of AMG 193, an MTA-Cooperative PRMT5 Inhibitor, in Patients with Advanced MTAP-Null Solid Tumors

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A phase 1 dose-escalation study is being conducted to evaluate the safety, tolerability, pharmacokinetics, pharmacodynamics, and efficacy of AMG 193, a methylthioadenosine-cooperative PRMT5 inhibitor, in patients with advanced methylthioadenosine phosphorylase (MTAP)-null solid tumors. MTAP deletion occurs in approximately 10%-15% of human cancers, leading to cellular buildup of the substrate methylthioadenosine (MTA), which can inhibit protein arginine methyltransferase 5 (PRMT5). MTA-cooperative PRMT5 inhibitors selectively inhibit PRMT5 in MTAP-null tumors, making them a potential therapeutic target. Preclinical experiments have shown that MTA-cooperative PRMT5 inhibitors preferentially inhibit cell viability in MTAP-null cancer cell lines and inhibit the growth of patient-derived tumor xenograft models.<br /><br />The study design consists of three parts, with part 1a focusing on dose exploration. Approximately 30 patients with eligible tumor types will be enrolled in part 1a, and the maximum tolerated dose (MTD) or recommended phase 2 dose (RP2D) of AMG 193 monotherapy will be determined. The study will also evaluate the pharmacokinetic parameters of AMG 193.<br /><br />Primary objectives of the study include evaluating the safety, tolerability, and determining the MTD or RP2D of AMG 193 monotherapy. Secondary objectives include characterizing the pharmacokinetic parameters of AMG 193 after single and multiple doses.<br /><br />The study is open for enrollment, and the first trial of this new class of MTA-cooperative PRMT5 inhibitors. Key inclusion criteria include having locally advanced or metastatic solid tumors that are not amenable to curative treatment, homozygous MTAP and/or CDKN2A deletion, measurable disease, and Eastern Cooperative Oncology Group performance status of 0 or 1.<br /><br />The study will provide valuable information on the safety and efficacy of AMG 193 in patients with MTAP-null solid tumors.

Asset Subtitle

Miguel Villalona Calero

Meta Tag

Speaker Miguel Villalona Calero

Topic Metastatic Non-small Cell Lung Cancer - Molecular Targeted Treatments

Keywords

phase 1

dose-escalation study

AMG 193

methylthioadenosine-cooperative PRMT5 inhibitor

MTAP-null solid tumors

MTAP deletion

MTA-cooperative PRMT5 inhibitors

maximum tolerated dose

recommended phase 2 dose

pharmacokinetic parameters