As reported in the Journal of Clinical Oncology by Sands et al, the phase II TROPION-Lung05 trial showed “encouraging activity” of datopotamab deruxtecan (Dato-DXd) in patients with advanced/metastatic non–small cell lung cancer (NSCLC) with actionable genomic alterations whose disease progressed after treatment with targeted therapy and platinum-based chemotherapy.
Dato-DXd is a trophoblast cell-surface antigen-2–directed antibody-drug conjugate with a topoisomerase I inhibitor payload.
Study Details
In the multinational trial, 137 patients enrolled between March 2021 and December 2022 received Dato-DXd at 6 mg/kg every 3 weeks until disease progression or unacceptable toxicity. Among the 137 patients, 71.5% had received three or more lines of prior therapy for advanced/metastatic disease. Overall, 78 patients (56.9%) had EGFR mutations and 34 (24.8%) had ALK rearrangements The primary endpoint was objective response on blinded independent central review.
Key Findings
Among all patients, the confirmed objective response rate was 35.8% (95% confidence interval [CI] = 27.8%–44.4%), including rates of 43.6% (95% CI = 32.4%–55.3%) among those with EGFR mutations and 23.5% (95% CI = 10.7%–41.2%) among those with ALK rearrangements. Disease control rates were 78.8% overall, 82.1% among patients with EGFR mutations, and 73.5% among those with ALK alterations. Among all responders, median duration of response was 7.0 months (95% CI = 4.2–9.8 months), with a median duration of 7.0 months (95% CI = 4.2–10.2 months) among patients with EGFR mutations and 7.0 months (95% CI = 2.8–8.4 months) among those with ALK alterations.
The most common treatment-related adverse events of any grade were stomatitis (in 56.2% of patients), nausea (54.7%), alopecia (49.6%), decreased appetite (20.4%), and fatigue (19.0%). Grade ≥ 3 treatment-related adverse events occurred in 28.5% of patients, most commonly stomatitis (9.5%), nausea (2.2%), and decreased appetite (2.2%). Treatment-related adverse events led to treatment discontinuation in seven patients (5.1%). Treatment-related interstitial lung disease/pneumonitis occurred in five patients (3.6%), with death occurring in one.
The investigators concluded: “Encouraging and durable antitumor activity was observed with Dato-DXd in this heavily pretreated advanced/metastatic NSCLC population with actionable genomic alterations. The rate of treatment-related grade ≥ 3 toxicities was comparable with previous observations, and no new safety signals were observed.”
Jacob Sands, MD, of Dana-Farber Cancer Institute, is the corresponding author for the Journal of Clinical Oncology article.
Disclosure: The study was supported by Daiichi Sankyo, Inc. In July 2020, AstraZeneca entered into a global development and commercialization collaboration agreement with Daiichi Sankyo, Inc, for Dato-DXd. For full disclosures of the study authors, visit ascopubs.org.
