TROP-2–Directed Antibody-Drug Conjugate Datopotamab Deruxtecan in Advanced NSCLC

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In a phase I study (TROPION-PanTumor01) reported in the Journal of Clinical Oncology, Shimizu et al described outcomes with the trophoblast cell-surface antigen 2 (TROP-2)-directed antibody-drug conjugate datopotamab deruxtecan at the dose selected for further development in patients with advanced non–small cell lung cancer (NSCLC).

Study Details

In the multicenter study conducted at sites in the United States and Japan, 180 patients with locally advanced or metastatic NSCLC enrolled between February 2018 and October 2020 received datopotamab deruxtecan once every 3 weeks at 4 (n = 50), 6 (n = 50), or 8 mg/kg (n = 80) during expansion. Patients had a median of three prior lines of therapy.

Key Findings

The maximum tolerated dose was 8 mg/kg every 3 weeks, with the 6 mg/kg every-3-weeks dose selected as the dose for further development. Among 50 patients receiving 6 mg/kg every 3 weeks, the median duration on study was 13.3 months and median exposure to treatment was 3.5 months.

The most common any-grade adverse events in the 6 mg/kg group were nausea (64%), stomatitis (60%), and alopecia (42%), and fatigue (28%). Grade ≥ 3 adverse events occurred in 54% of patients, most commonly nausea (4%) and anemia (4%). Adverse events led to discontinuation of treatment in 14% of patients. Interstitial lung disease adjudicated as drug-related occurred in three patients (6%; grade 2 in two patients, grade 4 in one).

Confirmed objective responses (all partial) were observed in 13 (26%, 95% confidence interval [CI] = 14.6%–40.3%) of 50 patients. Responses were observed regardless of TROP2 expression. Confirmed objective responses and those pending confirmation were observed in 16 patients (32%). An additional 20 patients (40%) had stable disease, and the disease control rate was 70%. Median duration of response was 10.5 months (95% CI = 5.6–26.5 months). Median progression-free survival was 6.9 months (95% CI = 2.7–8.8 months), and median overall survival was 11.4 months (95% CI = 7.1–20.6 months).

The investigators concluded, “Promising antitumor activity and a manageable safety profile were seen with datopotamab deruxtecan in heavily pretreated patients with advanced NSCLC. Further investigation as first-line combination therapy in advanced NSCLC and as monotherapy in the second-line setting and beyond is ongoing.”

Toshio Shimizu, MD, PhD, of the Department of Pulmonary Medicine and Medical Oncology, Wakayama Medical University Hospital, Wakayama, is the corresponding author for the Journal of Clinical Oncology article.

Disclosure: The study was supported by Daiichi Sankyo, Inc, and AstraZeneca. For full disclosures of the study authors, visit