Datopotamab Deruxtecan Improves PFS Vs Docetaxel in Advanced NSCLC

Investigators of the global, multi-center, open-label, randomized phase 3 TROPION-Lung01 trial are assessing the safety and efficacy of dato-DXd compared with docetaxel among those with locally advanced or metastatic NSCLC regardless of the presence of actionable genomic alterations.

Treatment with datopotamab deruxtecan (dato-DXd; DS-1062a) led to a statistically significant improvement in progression-free survival (PFS) compared with docetaxel among patients with locally advanced or metastatic non–small cell lung cancer (NSCLC) who have received at least 1 prior line of therapy, according to a press release on data from the phase 3 TROPION-Lung01 trial (NCT04656652).

The overall survival (OS) data were not mature at the time of the analysis, although investigators noted an early trend in favor of dato-DXd that was not statistically significant. The trial will proceed with further evaluation of OS, and investigators and patients will still be blinded to the results.

Dato-DXd did not yield any new safety signals, according to the trial’s initial phase 3 results. Any-grade interstitial lung disease in the TROPION-Lung01 study was comparable with reports in previous trials, and most instances were low grade. Moreover, investigators observed several grade 5 events.

“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 Research and Development at Daiichi Sankyo, said in the press release. “We plan to share these data with regulatory authorities to discuss next steps.”

Investigators of the global, multi-center, open-label, randomized phase 3 TROPION-Lung01 trial are assessing the safety and efficacy of dato-DXd compared with docetaxel among those with locally advanced or metastatic NSCLC regardless of the presence of actionable genomic alterations. Patients were randomly assigned to receive 6.0 mg/kg of dato-DXd intravenously or 75 mg/m2 of docetaxel intravenously on day 1 of each 3-week cycle.

The primary end points of the trial were PFS as assessed by blinded independent central review based on RECIST v1.1 criteria and OS. Secondary end points included objective response rate, duration of response, disease control rate, time to response, time to deterioration, and treatment-emergent adverse effects.

Patients 18 years and older with pathologically documented stage IIIB, IIIC, or stage IV NSCLC and a life expectancy of at least 3 months were able to enroll on the trial. Additional eligibility criteria included having measurable disease per RECIST v1.1 criteria; an ECOG performance status of 0 or 1; adequate bone marrow, hepatic, and renal function; adequate blood clotting function; and adequate treatment washout period prior to randomization.

Patients with mixed small cell lung cancer and NSCLC histology and those with spinal cord compression or clinically active central nervous system metastases were unable to enroll on the trial. Patients were also unsuitable for enrollment if they had leptomeningeal carcinomatosis or metastasis, any prior treatment with platinum-containing chemotherapy and immunotherapy for stage II NSCLC, uncontrolled or significant cardiac disease, or clinically significant corneal disease.

Developers of dato-DXd are conducting an international development program, which includes more than 12 clinical trials assessing the agent across TROP-2 targetable cancer types such as NSCLC, triple-negative breast cancer, and hormone receptor–positive HER2-low breast cancer. Additionally, investigators are evaluating Dato-DXd in combination with immune checkpoint inhibitors among patients with NSCLC in the phase 3 TROPION-Lung07 trial (NCT05555732), the phase 3 TROPION-Lung08 trial (NCT05215340), and the phase 3 AVANZAR trial (NCT05687266).

“These first phase 3 trial results from the datopotamab deruxtecan clinical program provide compelling evidence for the potential role this TROP2-directed antibody drug conjugate can play in treating patients with lung cancer,” Susan Galbraith, executive vice president of Oncology Research and Development at AstraZeneca, concluded.

Reference

Datopotamab deruxtecan met dual primary endpoint of progression-free survival in patients with advanced non-small cell lung cancer in TROPION-Lung01 Phase III trial. News release. AstraZeneca. July 3, 2023. Accessed July 5, 2023. https://shorturl.at/DPY29