Datopotamab deruxtecan was effective in patients with TROP2-QCS biomarker-positive tumors for non–small cell lung cancer
According to an exploratory analysis of the TROPION-Lung01 (NCT04656652) phase 3 trial, TROP2—a protein expressed in non-small cell lung cancer (NSCLC) on the surface and inside of tumor cells—was found to be predictive of clinical outcomes in patients with advanced or metastatic NSCLC who were treated with datopotamab deruxtecan (dato-DXd).1
In patients with TROP2-QCS biomarker-positive tumors, dato-DXd was found to demonstrate a meaningfully greater magnitude of efficacy compared with docetaxel than in the overall trial population. These results were featured in a Presidential Symposium at the 2024 World Conference on Lung Cancer in San Diego, California.1
“We have shown with this analysis that the more precise quantitative measurement of TROP2 on and inside tumor cells, enabled by AstraZeneca’s computational pathology platform, can identify which patients with non–small cell lung cancer are most likely to benefit from treatment with datopotamab deruxtecan,” Marina Garassino, MD, investigator in the trial, said in a news release from AstraZeneca.1
Dato-DXd is an engineered TROP2-directed antibody drug conjugate that was discovered by Daiichi Sankyo and is being developed in collaboration with AstraZeneca. It is comprised of a humanized anti-TROP2 monoclonal antibody.2
Through quantitative continuous scoring (QCS), a computational pathology platform developed by AstraZeneca, the study investigators were able to successfully analyze tissue samples and determine patients who were considered TROP2-QCS biomarker positive. QCS digitally analyzes images of patient tissue samples and quantifies targets such as TROP2 on the surface of and inside every tumor cell in the body.2
QCS analysis in the TROPION-Lung01 trial produced a normalized membrane ratio for each tumor cell in the sample. Observations indicated that a greater proportion of patients with non-squamous NSCLC were considered TROP2-QCS biomarker positive than those with squamous NSCLC. Because the subgroup of patients with non-squamous NSCLC represented a significant unmet medical need, the threshold for biomarker positivity was optimized for progression-free survival.2
Trial Name: Study of DS-1062a Versus Docetaxel in Previously Treated Advanced or Metastatic Non-small Cell Lung Cancer With or Without Actionable Genomic Alterations (TROPION-LUNG01)
ClinicalTrials.gov ID: NCT04656652
Sponsor: Daiichi Sankyo
Estimated Completion: June 21, 2025
In patients who were identified as positive for TROP2-QCS biomarker, dato-DXd reduced the risk of disease progression or death by 43% compared with docetaxel. Comparatively, in the overall trial population, dato-DXd reduced disease progression risk or death by 25% versus docetaxel.1,2
In a news release from Daiichi Sankyo, Ken Takeshita, MD, global head of R&D, said, “the results from the QCS analysis support the potential of TROP2, as measured by quantitative continuous scoring, as a predictive biomarker for datopotamab deruxtecan and begin to answer the question of why certain patients with non–small cell lung cancer respond better to treatment.”2
There were no new safety concerns identified in the biomarker evaluable population. Additionally, rates of grade 3 or higher treatment-related adverse events (TRAE) were similar regardless of a patient’s TROP2 status. In those with TROP2-QCS biomarker-positive tumors, grade 3 or higher TRAEs were observed in 30% and 46% of patients in the dato-DXd and docetaxel arms, respectively, according to the press releases.1,2
In a companion announcement, AstraZeneca and Roche Tissue Diagnostics agreed to collaborate to co-develop and commercialize the TROP2-QCS biomarker companion diagnostic. This device is poised to aid pathologists in interpreting TROP2 assays and better determining patient biomarker status.1
“By developing an innovative Al tool that goes beyond human capabilities, the solution will be able to help determine which cancer patients are most likely to benefit from targeted therapies, potentially improving patient care,” Jill German, head of Roche Tissue Diagnostics, said in the news release.1
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