2024 World Conference on Lung Cancer (WCLC) - Posters-P3.12D.11 Phase 1/2, Dose-expansion Study of AMG 193, an MTA-cooperative PRMT5 Inhibitor, In MTAP-deleted NSCLC

P3.12D.11 Phase 1/2, Dose-expansion Study of AMG 193, an MTA-cooperative PRMT5 Inhibitor, In MTAP-deleted NSCLC

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The document provides an overview of a Phase 1/2 clinical study led by Dr. Adrian Sacher of the Princess Margaret Cancer Centre, investigating AMG 193, an oral inhibitor designed for the treatment of MTAP-deleted cancers, particularly non-small cell lung cancer (NSCLC). AMG 193 is a CNS-penetrant inhibitor targeting protein arginine methyltransferase 5 (PRMT5), which is known to be dysregulated in cancer cells. Unlike first-generation PRMT5 inhibitors that were nonspecific and caused significant hematological toxicities, AMG 193 selectively inhibits PRMT5 when bound to S-methyl-5'-thioadenosine (MTA), potentially reducing off-target effects.<br /><br />AMG 193 exploits a specific vulnerability in cancer cells due to the deletion of MTAP, leading to MTA accumulation. This not only inhibits PRMT5 naturally but also enhances AMG 193's selectivity for cancer cells, thus sparing normal cells. Preclinical models have shown promising selective antitumor activity. Initial human trials showed a favorable safety profile and efficacy in MTAP-deleted tumors without dose-limiting myelosuppression.<br /><br />The study aims to assess the safety, tolerability, and pharmacokinetics (PK) of AMG 193, along with its preliminary antitumor activity in patients with advanced solid tumors lacking MTAP. Key inclusion criteria include adult patients with confirmed MTAP-deleted tumors, prior systemic therapy, and certain performance statuses. The trials are conducted globally across 58 sites, focusing on endpoints such as dose-limiting toxicities, treatment-emergent adverse events, and overall survival.<br /><br />This research is funded by Amgen Inc. For further details, reference to ClinicalTrials.gov or direct communications are suggested.

Asset Subtitle

Adrian Sacher

Meta Tag

Speaker Adrian Sacher

Topic Metastatic NSCLC – Targeted Therapy

Keywords

Phase 1/2 clinical study

AMG 193

MTAP-deleted cancers

non-small cell lung cancer

PRMT5 inhibitor

CNS-penetrant

antitumor activity

safety and tolerability

Amgen Inc.

ClinicalTrials.gov