Datopotamab Deruxtecan Significantly Improves PFS in Advanced NSCLC

Datopotamab deruxtecan (Dato-DXd; DS-1062a) provided a statistically significant improvement in progression-free survival (PFS) compared with standard-of-care docetaxel in patients with locally advanced or metastatic non–small cell lung cancer (NSCLC) who received at least 1 prior line of therapy, meeting a primary end point of the phase 3 TROPION-Lung01 trial (NCT04656652).¹

Data for the other primary end point of overall survival (OS) remained immature. However, a trend in favor of datopotamab deruxtecan did not reach a prespecified threshold for statistical significance at the time of this interim analysis. Assessment of OS is ongoing, and the study is still blinded.

“We are encouraged by the statistically significant results of the dual primary end point of PFS seen with datopotamab deruxtecan and look forward to the final OS analysis,” Ken Takeshita, MD, global head of Oncology R&D at Daiichi Sankyo, stated in a news release. “We plan to share these data with regulatory authorities to discuss next steps.”

The global, randomized, multicenter, open-label TROPION-Lung01 study enrolled patients at least 18 years of age with pathologically documented stage IIIB, IIIC, or IV NSCLC with or without actionable genomic alterations. Those with a known genomic alteration, including EGFR, ALK, ROS1, NTRK, BRAF, MET exon 14 skipping, or RET, were required to have received prior platinum-based chemotherapy and an approved targeted therapy, and those without these alterations needed to have received concurrent or sequential platinum-based chemotherapy and a PD-1/PD-L1 inhibitor.²

Other key inclusion criteria included documented radiographic disease progression on or after the most recent treatment for advanced NSCLC; measurable disease per RECIST v1.1 criteria; an ECOG performance status of 0 or 1; adequate bone marrow, hepatic, and renal function; and a life expectancy of at least 3 months.

Patients were excluded if they had mixed small cell and non–small cell histology, had spinal cord compression or clinically active central nervous system metastases, had leptomeningeal carcinomatosis or metastasis, or received prior treatment with an antibody-drug conjugate (ADC) featuring a chemotherapeutic agent targeting topoisomerase I, a Trop-2–targeted therapy, or docetaxel.

The study enrolled approximately 600 patients at sites in Asia, Europe, North America, and South America. Patients were randomly assigned to receive 6.0 mg/kg of datopotamab deruxtecan once every 3 weeks or 75 mg/m² of docetaxel once every 3 weeks.

Along with the dual primary end points of PFS per blinded independent central review (BICR) and OS, secondary end points included investigator-assessed PFS, objective response rate, duration of response, time to response, disease control rate per BICR and investigator assessment, and safety.

“With TROPION-Lung01, we met the dual primary end point of PFS, challenging the entrenched standard of care in a previously treated and unselected patient population that has long deserved an alternative to chemotherapy,” Susan Galbraith, MBBChir, PhD, executive vice president of Oncology R&D at AstraZeneca, stated in a news release. “These first phase 3 trial results from the datopotamab deruxtecan clinical program provide compelling evidence for the potential role this TROP2 directed ADC can play in treating patients with lung cancer.”

References

1. Datopotamab deruxtecan met dual primary endpoint of progression-free survival in patients with advanced non small cell lung cancer in TROPION-Lung01 phase 3 trial. News release. Daiichi Sankyo. July 3, 2023. Accessed July 5, 2023. https://www.daiichisankyo.com/files/news/pressrelease/pdf/202307/20230703_E.pdf
2. 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. Updated July 4, 2023. Accessed July 5, 2023. https://clinicaltrials.gov/study/NCT04656652