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Results from the TROPION-Lung01 Phase III trial (NCT04656652) show datopotamab deruxtecan (Dato-DXd) achieved superior overall survival (OS) compared to current standard of care docetaxel in a population of patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) previously administered at least one line of therapy. Further, a prespecified subgroup of patients with nonsquamous NSCLC who were administered datopotamab deruxtecan showed a clinically meaningful improvement in OS vs. docetaxel. However, in the overall trial population, survival results for datopotamab deruxtecan did not achieve statistical significance.1
Findings from the trial released in October 2023 showed datopotamab deruxtecan achieved a statistically significant improvement in the trial’s primary endpoint of progression-free survival (PFS) vs. docetaxel in patients with locally advanced or metastatic NSCLC previously administered at least one line of therapy.2
“Datopotamab deruxtecan is the only investigational therapy to show a clinically meaningful survival improvement in patients with previously treated nonsquamous non-small cell lung cancer versus docetaxel, which has long been unsurpassed in this post-targeted treatment and post-immunotherapy setting,” said Susan Galbraith, executive vice president, Oncology R&D, AstraZeneca, in a press release. “These results reinforce the potential for datopotamab deruxtecan to replace conventional chemotherapy in this late-line setting and underscore our confidence in ongoing trials evaluating this therapy in first-line lung cancer.”1
The global, randomized, multicenter, open-label trial enrolled approximately 600 patients across sites in Asia, Europe, North America, and South America. Investigators compared the efficacy and safety of datopotamab deruxtecan at a dose of 6.0 mg/kg with docetaxel at a dose of 75 mg/m2 in adults with locally advanced or metastatic NSCLC, with and without actionable genomic alterations, who were in need of systemic therapy after previous treatment. Those with actionable genomic alterations received prior treatment with platinum-based chemotherapy and an approved targeted therapy, whereas those without known actionable genomic alterations received prior treatment, concurrently or sequentially, with platinum-based chemotherapy and a PD-1 or PD-L1 inhibitor.
The trial’s dual primary endpoints are PFS as assessed by blinded independent central review (BICR) and OS, with key secondary endpoints that include investigator-assessed PFS, objective response rate (ORR), duration of response, time to response, disease control rate as assessed by both BICR and investigator, and safety.
Results released in 2023 show datopotamab deruxtecan lowered the risk of disease progression or death by 25% vs. docetaxel (hazard ratio [HR] 0.75; 95% confidence interval [CI] 0.62-0.91; p=0.004) as assessed by BICR. Patients administered datopotamab deruxtecan had a median PFS of 4.4 months compared with 3.7 months in the docetaxel cohort. Confirmed ORR was 26.4% in the datopotamab deruxtecan cohort vs. 12.8% in the docetaxel cohort.
Datopotamab deruxtecan lowered the risk of disease progression or death by 37% in patients with non-squamous NSCLC compared with docetaxel (HR 0.63; 95% CI 0.51-0.78), with median PFS among this group at 5.6 months in the datopotamab deruxtecan cohort compared with 3.7 in the docetaxel cohort.
Confirmed ORR was 31.2% in the datopotamab deruxtecan cohort, which included four complete responses (CRs), compared with 12.8% in the docetaxel cohort with no CRs. However, datopotamab deruxtecan did not achieve a PFS benefit in patients with squamous NSCLC.2
“The improvement in overall survival seen with datopotamab deruxtecan 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 nonsquamous non-small cell lung cancer in this advanced setting,” said Ken Takeshita, MD, global head, R&D, Daiichi Sankyo, in the release. “These data will support our ongoing discussions with regulatory authorities globally to potentially bring datopotamab deruxtecan to patients as quickly as possible and mark another step forward in creating new standards of care for patients with cancer.”1
References
1. Datopotamab deruxtecan showed clinically meaningful overall survival improvement vs. chemotherapy in patients with advanced nonsquamous non-small cell lung cancer in TROPION-Lung01 Phase III trial. News release. AstraZeneca. May 27, 2024. Accessed May 30, 2024. https://www.astrazeneca.com/media-centre/press-releases/2024/dato-dxd-improved-os-in-nonsquamous-lung-cancer.html#!
2. Datopotamab deruxtecan improved progression-free survival vs. chemotherapy in patients with previously treated non-small cell lung cancer in TROPION-Lung01 Phase III trial. News release. AstraZeneca. October 23, 2023. Accessed May 30, 2024. https://www.astrazeneca.com/media-centre/press-releases/2023/datopotamab-deruxtecan-improved-progression-free-survival-vs-chemotherapy-in-tropion-lung01-phase-iii-trial.html
