TROPION-Lung07 Study Launched to Evaluate Safety, Efficacy of Datopotamab Deruxtecan Addition to Existing Treatments for NSCLC

A new study is aiming to identify additional therapeutic combination strategies targeted toward patients with advanced or metastatic non-squamous non-small cell lung cancer (NSCLC) who have low PD-L1 expression.

TROPION-Lung07, a randomized, open-label, phase 3 study is assessing datopotamab deruxtecan (Dato-DXd), which is a TROP2-directed antibody-drug conjugate, in combination with pembrolizumab and with or without chemotherapy, as well as pembrolizumab plus pemetrexed and chemotherapy, for safety and efficacy in patients with advanced or metastatic NSCLC who have less than 50% PD-L1 expression and no actionable genomic alterations.

The trial will enroll patients at 250 sites across North America, South America, Europe, east Asia, and Australia, aiming for a total of 1,170 eligible patients. To participate, patients have to be 18 years or older; have histologically confirmed non-squamous NSCLC; have low PD-L1 expression of either stage IV, stage IIIB, or IIIC; and not be a candidate for surgery or definitive chemoradiation.

The primary objectives of the ongoing study are progression-free survival (PFS) and overall survival. The secondary objectives key to exploring treatment efficacy are objective response rate and blinded independent central review. Additional secondary objectives are duration of response, time to response, disease control rate, and PFS2. The study will also examine patient-reported outcomes, such as cough, dyspnea, chest pain, and treatment-emergent adverse events.

The researchers will also investigate exploratory objectives, such as “evaluation of biomarkers and pharmacogenetics and pharmacokinetic exposures for potential association with efficacy and safety, and exploring how changes in biomarkers may relate to exposure, AEs, and clinical outcomes.”

There will be 390 patients in each treatment arm. The first cohort will be treated with pembrolizumab plus chemotherapy, the second cohort will receive Dato-DXd plus pembrolizumab, and the third cohort will be treated with Dato-DXd plus pembrolizumab and chemotherapy. The patients in each group will be randomized 1:1:1.

The study results may provide investigators with more insight and understanding about whether the addition of Dato-DXd to other anticancer drugs will extend life without disease progression in patients with advanced or metastatic NSCLC who lack actionable genomic alterations.

Furthermore, the researchers stated that “the outcomes of this study will help establish whether the Dato-DXd doublet and/or triplet regimens may replace the platinum doublet and/or the platinum partner in combination with pembrolizumab therapy as first-line treatment for patients with advanced or metastatic NSCLC.”

Source: Future Oncology