Datopotamab Deruxtecan Achieves 14.6-Month Median Survival in Advanced Nonsquamous NSCLC TROPION-Lung01 Trial

In recent developments from TOKYO and BASKING RIDGE, N.J., detailed results from the TROPION-Lung01 phase 3 trial have showcased promising advancements for the treatment of advanced non-small cell lung cancer (NSCLC). This significant trial, focusing on the efficacy of datopotamab deruxtecan (Dato-DXd), was presented at the IASLC 2024 World Conference on Lung Cancer and simultaneously published in the Journal of Clinical Oncology.

The TROPION-Lung01 trial evaluated the performance of datopotamab deruxtecan against docetaxel, a standard chemotherapy treatment, in patients with locally advanced or metastatic nonsquamous NSCLC who had previously undergone at least one line of therapy. This ADC (antibody-drug conjugate), specifically engineered to target TROP2, was discovered by Daiichi Sankyo and is being developed in collaboration with AstraZeneca.

Key findings from the trial revealed that while overall survival (OS) improved numerically with datopotamab deruxtecan compared to docetaxel (median OS of 12.9 months versus 11.8 months), the results did not reach statistical significance. The hazard ratio (HR) was reported at 0.94, with a 95% confidence interval (CI) of 0.78-1.14 and a p-value of 0.530. However, in a pre-specified subgroup of patients with nonsquamous NSCLC, datopotamab deruxtecan showed a more notable improvement in OS, with a median OS of 14.6 months compared to 12.3 months for docetaxel (HR=0.84; 95% CI: 0.68-1.05).

The safety profile of datopotamab deruxtecan was consistent with previous analyses, showing lower rates of dose reduction and discontinuation due to adverse events compared to docetaxel. Treatment-related adverse events of grade 3 or higher were observed in 26% of patients treated with datopotamab deruxtecan, compared to 42% of those treated with docetaxel. Specifically, neutropenia and leukopenia were considerably less frequent in the datopotamab deruxtecan group.

This final analysis builds on earlier positive results for progression-free survival (PFS) presented at the ESMO 2023 Congress, where datopotamab deruxtecan demonstrated a significant improvement. These findings have been shared with health authorities currently reviewing applications for this indication.

Commenting on the results, Dr. Jacob Sands from the Dana-Farber Cancer Institute noted the clinical significance of these findings, highlighting the potential for datopotamab deruxtecan to improve survival outcomes in a patient population that has historically had limited treatment options. Dr. Ken Takeshita of Daiichi Sankyo and Dr. Susan Galbraith of AstraZeneca also emphasized the importance of these results in the broader context of NSCLC treatment, particularly for nonsquamous histology.

In the trial, patients were previously treated with various therapies, including platinum-based chemotherapy, anti-PD-1/PD-L1 therapy, and targeted therapies. Approximately 75% of enrolled patients had nonsquamous NSCLC, and 17% had tumors with actionable genomic alterations.

In addition to the TROPION-Lung01 trial, datopotamab deruxtecan has shown promise in combination therapies. Preliminary results from the NeoCOAST-2 phase 2 trial, which evaluated neoadjuvant durvalumab plus datopotamab deruxtecan and carboplatin in early-stage resectable NSCLC, indicated promising response rates and a manageable safety profile.

TROPION-Lung01 represents a significant step forward in the treatment of advanced NSCLC, particularly for patients with nonsquamous histology. The trial's comprehensive data underscores the potential of datopotamab deruxtecan to offer improved outcomes and supports ongoing efforts to develop targeted therapies for this challenging disease. With further investigation and regulatory review, datopotamab deruxtecan could become a new standard of care in the treatment of advanced NSCLC.