WCLC 2025 - Posters & ePosters-P3.18.22 TRIPL: Thoracic Radiotherapy and Inhibition of PD-1 and LAG-3 for Locally Advanced Non-Small Cell Lung Cancer

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This document outlines a Phase II clinical trial (TRIPL: NCT06865339) investigating the efficacy and safety of combining dual immune checkpoint inhibitors—cemiplimab (PD-1 inhibitor) and fianlimab (LAG-3 inhibitor)—with thoracic radiotherapy (RT) in patients with locally advanced non-small cell lung cancer (LA-NSCLC).<br /><br />Background: The current standard of care for LA-NSCLC involves concurrent chemoradiotherapy followed by consolidative durvalumab, a PD-L1 inhibitor. However, 5-year overall survival remains around 50%, with many patients unable to start or complete durvalumab. The SPRINT study demonstrated promising outcomes using pembrolizumab (PD-1 inhibitor) induction followed by risk-adapted RT and pembrolizumab consolidation, achieving a 1-year progression-free survival (PFS) of 76% and overall survival (OS) of 92%, with good tolerability.<br /><br />Rationale: Cemiplimab is an approved PD-1 inhibitor for advanced NSCLC; fianlimab targets LAG-3, another immune checkpoint. Early Phase I data suggest combining cemiplimab and fianlimab enhances antitumor activity with acceptable safety.<br /><br />Study Design: The TRIPL trial will enroll 76 treatment-naïve LA-NSCLC patients, divided into two cohorts based on PD-L1 tumor proportion score (TPS) ≥50% or <50%. Patients will receive dual-agent induction immunotherapy (cemiplimab plus fianlimab) followed by thoracic RT and consolidation immunotherapy for one year. Key inclusion criteria include biopsy-proven Stage II-III NSCLC, ECOG 0–2, and eligibility for nonsurgical treatment. Exclusions include known EGFR or ALK mutations and prior checkpoint inhibitor therapy.<br /><br />Objectives: The primary endpoint is objective response rate (ORR) assessed by PET imaging (30% maximum SUV reduction) post induction immunotherapy. Secondary endpoints include safety (dose-limiting toxicities), extended adverse event monitoring, and exploratory analyses such as CT response (RECIST 1.1), survival outcomes (OS, PFS), quality of life measures, and biomarker studies (circulating tumor DNA and immune signatures).<br /><br />The study is actively recruiting with the first patient enrolled in August 2025 across multiple sites including Montefiore Einstein Comprehensive Cancer Center. The hypothesis is that dual checkpoint inhibition plus RT will be a safe and effective treatment for LA-NSCLC, potentially improving outcomes beyond current standards.

Asset Subtitle

Angelica D'Aiello

Meta Tag

Speaker Angelica D'Aiello

Topic Clinical Trials in Progress

Keywords

Phase II clinical trial

TRIPL

NCT06865339

cemiplimab

fianlimab

dual immune checkpoint inhibitors

thoracic radiotherapy

locally advanced non-small cell lung cancer

PD-L1 tumor proportion score

objective response rate