2024 World Conference on Lung Cancer (WCLC) - Posters-P2.10A.04 Valemetostat and Datopotamab Deruxtecan in Previously Treated, Advanced, Unresectable, or Metastatic Non-squamous NSCLC

P2.10A.04 Valemetostat and Datopotamab Deruxtecan in Previously Treated, Advanced, Unresectable, or Metastatic Non-squamous NSCLC

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This document outlines a phase 1b clinical trial study examining the combination of valemetostat with the drug Datopotamab deruxtecan (Dato-DXd) in patients with advanced nonsquamous non-small-cell lung cancer (NSCLC). The study, currently enrolling participants in the US and Japan, explores the potential heightened efficacy and safety of this combination therapy for patients who have already undergone other treatments.<br /><br />### **Study Design**<br /><br />The trial consists of two parts: a dose-escalation phase followed by a dose-expansion phase. In Part 1, patients receive varying doses of oral valemetostat alongside a fixed dose of intravenous Dato-DXd every three weeks. Part 2 will administer these drugs at the optimal doses determined from Part 1.<br /><br />### **Eligibility Criteria**<br /><br />Inclusion criteria specify adults (18 years or older) with measurable lesions, ECOG performance status of 0–1, adequate organ function, and diagnosed with specific stages of NSCLC. They can have had prior targeted therapies or chemotherapies, provided they meet further genomic mutation specifications. However, patients with squamous histology, small-cell components, specific HER2 mutations, or prior exposure to TROP2-targeted therapies are excluded.<br /><br />### **Endpoints**<br /><br />The primary endpoints focus on safety, tolerability, and overall response rate (ORR). Secondary endpoints include progression-free survival (PFS), overall survival (OS), and pharmacokinetics (PK).<br /><br />### **Background & Objectives**<br /><br />Valemetostat, a dual inhibitor targeting EZH2/EZH1, aims to sensitize cancer cells to DNA-damaging agents present in Dato-DXd. Dato-DXd targets TROP2, an antigen commonly overexpressed in certain cancers, making it a promising candidate for NSCLC therapy. This trial seeks to establish whether valemetostat can boost Dato-DXd's effectiveness while maintaining a tolerable safety profile.<br /><br />This exploratory study aims to inform potential improvements in second-line or later treatments for advanced NSCLC and possibly other cancers.

Asset Subtitle

Alexander Spira

Meta Tag

Speaker Alexander Spira

Topic Metastatic NSCLC – Cytotoxic Therapy

Keywords

valemetostat

Datopotamab deruxtecan

NSCLC

clinical trial

dose-escalation

dose-expansion

TROP2

EZH2/EZH1

safety

efficacy