2024 World Conference on Lung Cancer (WCLC) - ePosters-EP.12H.09 Phase 1b/2a Study of ATR Inhibitor Tuvusertib + Anti-PD-1 Cemiplimab in Patients with Advanced Non-Squamous NSCLC

EP.12H.09 Phase 1b/2a Study of ATR Inhibitor Tuvusertib + Anti-PD-1 Cemiplimab in Patients with Advanced Non-Squamous NSCLC

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The abstract describes the DDRiver NSCLC 322 Phase 1b/2a clinical trial, which is evaluating the combination of the ATR inhibitor, tuvusertib, and the anti-PD-L1 therapy, cemiplimab, for advanced non-squamous non-small cell lung cancer (NSCLC) that has progressed despite previous therapies. The trial, sponsored by Merck KGaA, Darmstadt, Germany, involves multiple centers across several countries, including the USA, Belgium, France, Germany, Spain, Italy, Japan, and South Korea.<br /><br />The study aims to address immune checkpoint inhibitor (ICI) resistance in tumor cells, particularly those that have become resistant to conventional anti-PD-(L)1 therapies and platinum-based chemotherapy. The mechanism by which this combination is expected to work involves overcoming this resistance and promoting an anti-tumor immune response, potentially through ATR inhibition which induces DNA damage, resulting in increased type I interferon response and activation of immune pathways.<br /><br />Phase 1b focuses on identifying optimal dosing regimens, while Phase 2a stratifies patients based on specific tumor genetic alterations, such as mutations in STK11, KEAP1, ATM, ARID1A, SMARCA4, or PBRM1. Key endpoints include efficacy measured by progression-free survival (PFS), overall survival (OS), and safety/tolerability assessments.<br /><br />Key inclusion criteria include confirmed NSCLC with progression after prior therapies. Exclusion criteria include prior ATR, CHK1, or WEE1 inhibitor use and the presence of unstable brain metastases.<br /><br />Overall, the study is exploring a new therapeutic avenue for patients with limited options due to ICI resistance, with hopes of providing a biologically rationale combined treatment to overcome this significant hurdle in advanced NSCLC care.

Asset Subtitle

Natalie Vokes

Meta Tag

Speaker Natalie Vokes

Topic Metastatic Non-small Cell Lung Cancer – Targeted Therapy

Keywords

DDRiver NSCLC 322

clinical trial

ATR inhibitor

tuvusertib

anti-PD-L1 therapy

cemiplimab

immune checkpoint inhibitor resistance

advanced non-small cell lung cancer

Merck KGaA

tumor genetic alterations