Daiichi Sankyo & Astrazeneca Announced Results from the TROPION-Lung01 Phase 3 Trial

Daiichi Sankyo & Astrazeneca Announced Results from the TROPION-Lung01 Phase 3 Trial

By, Admin 10 September 2024

Daiichi Sankyo and AstraZeneca's New TROP2 Biomarker Predicts Datopotamab Deruxtecan Outcomes in NSCLC Trial

Overview

Daiichi Sankyo and AstraZeneca have announced results from the TROPION-Lung01 Phase 3 trial, showing that TROP2, measured using AstraZeneca’s Quantitative Continuous Scoring (QCS) system, can help predict treatment outcomes for patients with advanced or metastatic non-small cell lung cancer (NSCLC) treated with datopotamab deruxtecan (Dato-DXd).

TROPION-Lung01 Trial

  • TROPION-Lung01 is a global phase 3 trial comparing the efficacy and safety of datopotamab deruxtecan (6.0 mg/kg) with docetaxel (75 mg/m²) in adults with advanced or metastatic non-small cell lung cancer (NSCLC). 
  • The trial includes patients with and without actionable genomic alterations who need systemic therapy after previous treatments.

Lung Cancer Cases in 2022

  • In 2022, nearly 2.5 million global lung cancer cases were diagnosed, with non-small cell lung cancer (NSCLC) making up 80%. 
  • While immunotherapy and targeted treatments have improved early outcomes, most patients still progress to chemotherapy, which has limited effectiveness.
  • TROP2 is commonly found in NSCLC, but no TROP2-targeting therapies are yet approved.

Datopotamab Deruxtecan

  • Datopotamab deruxtecan (Dato-DXd) is an investigational TROP2-targeting antibody-drug conjugate (ADC) using Daiichi Sankyo’s DXd technology. 
  • It combines an anti-TROP2 antibody with a topoisomerase I inhibitor. 
  • Over 20 global trials are underway, including seven Phase 3 studies in lung cancer and five in breast cancer.

In patients with TROP2-QCS biomarker-positive tumours, datopotamab deruxtecan showed significantly better efficacy than docetaxel. These findings will be presented at the IASLC 2024 World Conference on Lung Cancer.

Datopotamab Deruxtecan & TROP2

  • Datopotamab deruxtecan, developed by Daiichi Sankyo and AstraZeneca, is a TROP2-targeting antibody-drug conjugate (ADC) designed for NSCLC. TROP2 is a protein commonly found in NSCLC tumours. 
  • While traditional methods using immunohistochemistry have not been predictive, AstraZeneca’s QCS platform offers more precise measurement of TROP2, improving patient selection.

Analysis Results

  • The analysis revealed that more patients with nonsquamous NSCLC (66%) were TROP2-QCS positive compared to those with squamous NSCLC (44%). 
  • In these patients, datopotamab deruxtecan reduced the risk of disease progression or death by 43% versus docetaxel, with a median progression-free survival (PFS) of 6.9 months versus 4.1 months. 
  • In the overall trial population, datopotamab deruxtecan reduced the risk by 25%.

This analysis shows how precise TROP2 measurement using QCS can identify patients most likely to benefit from datopotamab deruxtecan. No new safety concerns were found, with similar rates of severe treatment-related side effects in both groups.

These findings suggest TROP2-QCS could guide better treatment decisions for NSCLC patients.

The Partnership

  • In March 2019, Daiichi Sankyo and AstraZeneca began a global partnership to develop and commercialise ENHERTU. 
  • They expanded this collaboration in July 2020 to include datopotamab deruxtecan (Dato-DXd), except in Japan where Daiichi Sankyo retains exclusive rights. 
  • Daiichi Sankyo handles the manufacturing and supply of both ADCs.