AstraZeneca and Daiichi Sankyo Announce Clinical Milestone in Phase 3 Study of Datopotamab Deruxtecan Versus Chemotherapy for Lung Cancer

Results from the global TROPION-Lung01 Phase III trial were announced recently demonstrating that datopotamab deruxtecan (Dato-DXd) significantly improves overall survival compared to chemotherapy in patients with advanced non-squamous non-small cell lung cancer (NSCLC).

The study evaluated the efficacy and safety of Dato-DXd compared to docetaxel in adult patients with locally advanced or metastatic NSCLC with and without actionable genomic alterations who require systemic therapy following prior treatment.

Lung cancer is one of the leading causes of cancer-related deaths worldwide.

NSCLC is the most common type, accounting for 80% of diagnosed lung cancer cases. Chemotherapy has long been the standard treatment for advanced NSCLC, but new advancements in targeted therapies are showing promising results in improving overall survival rates.

Although immunotherapy and targeted therapies have shown improvement in outcomes for patients with advanced NSCLC in the first-line setting, many patients eventually require chemotherapy after experiencing disease progression.

Despite its limited effectiveness and known side effects, chemotherapy has traditionally been the last treatment option available for these patients.

Dato-DXd is a novel antibody-drug conjugate that targets trophoblast cell-surface antigen 2 (TROP2) overexpressed in cancer cells. Of note, TROP2 is a protein broadly expressed in most NSCLC tumors.

By delivering a potent cytotoxic agent, topoisomerase I inhibitor, directly to cancer cells, the drug is designed to effectively kill cancer cells while minimizing damage to healthy cells.

The trial included patients with advanced or metastatic NSCLC who had previously received platinum-based chemotherapy and an immune checkpoint inhibitor.

Patients were randomized to receive either Dato-DXd or a chemotherapy regimen consisting of docetaxel.

The experimental Dato-DXd drug had shown significant improvement in survival rates compared to standard chemotherapy in patients enrolled in the TROPION-Lung01 Phase III trial. Statistical significance, however, was not reached.

Additionally, the drug demonstrated a favorable safety profile, with manageable side effects reported by patients.

If approved by regulatory authorities, Dato-DXd could potentially become a new standard of care for patients with this challenging form of lung cancer.

“The improvement in overall survival seen with Dato-DXd coupled with the previously reported clinically meaningful progression-free survival, more than doubling of overall response and prolonged duration of response compared to docetaxel suggest that this TROP2-directed antibody drug conjugate could potentially become an important new treatment for patients with NSCLC in this advanced setting," Ken Takeshita, M.D., Global Head, R&D, Daiichi Sankyo, said in a press release.

"These data will support our ongoing discussions with regulatory authorities globally to potentially bring Dato-DXd to patients as quickly as possible and mark another step forward in creating new standards of care for patients with cancer."

Further research is needed to confirm the efficacy and safety of Dato-DXd in larger patient populations, but the positive results from the TROPION-Lung01 trial offer a promising outlook for the future of advanced NSCLC treatment.

Dato-DXd is currently being studied in over 20 clinical trials to determine its effectiveness and safety in various types of cancer, such as non-small cell lung cancer, triple-negative breast cancer and hormone receptor-positive, HER2-negative breast cancer.

If approved by the FDA, Dato-DXd would be a second-line therapy in NSCLC and available in intravenous form. No TROP-2- directed ADC therapies are currently approved for the treatment of patients with NSCLC.

The FDA has assigned a target action date of December 20th, 2024.