Datopotamab deruxtecan (Dato-DXd) has shown promising antitumor activity and a tolerable safety profile in patients with advanced or metastatic ovarian and endometrial cancers who have progressed after platinum-based chemotherapy. These findings were presented at the 2024 ESMO Congress from the phase 2 TROPION-PanTumor03 study (NCT05489211).
The global, open-label TROPION-PanTumor03 study is evaluating Dato-DXd as a monotherapy and in combination with other anticancer treatments across various tumor types. The presented results focused on the ovarian and endometrial cancer cohorts, where patients were unselected for TROP2 expression and had received one or two prior lines of therapy for advanced or metastatic disease.
Efficacy in Ovarian Cancer
In the ovarian cancer cohort (n = 35), the confirmed objective response rate (ORR) was 42.9% (95% CI, 26.3%-60.6%) at a median follow-up of 14.5 months. This included a complete response (CR) rate of 2.9% and a partial response (PR) rate of 40.0%. The median time to response was 1.4 months, and the median duration of response (DOR) was 5.7 months (95% CI, 2.9-NC). The disease control rate (DCR) was 85.7%.
Notably, among platinum-sensitive patients (n = 9), the ORR was 66.7% (95% CI, 29.9-92.5), compared to 34.6% (95% CI, 17.2-55.7) in platinum-resistant patients (n = 26). The median DOR was 8.5 months and 5.6 months, respectively. The median progression-free survival (PFS) in the overall ovarian cancer cohort was 5.6 months (95% CI, 4.1-7.0).
Efficacy in Endometrial Cancer
For the endometrial cancer cohort (n = 40), the confirmed ORR was 27.5% (95% CI, 14.6%-43.9%) at a median follow-up of 13.6 months, including a CR rate of 2.5% and a PR rate of 25.0%. The DCR was 57.5%, the median time to response was 2.8 months, and the median DOR was 16.4 months (95% CI, 7.1-NC). The median PFS was 6.3 months (95% CI, 2.8-NC).
Safety and Tolerability
The median duration of therapy was 5.6 months for the ovarian cohort and 5.2 months for the endometrial cohort. Grade 3 or higher treatment-emergent adverse events (TEAEs) occurred in 54.3% and 57.5% of the ovarian and endometrial cohorts, respectively. Serious TEAEs occurred in 28.6% and 27.5%, respectively. TEAEs leading to dose reduction, interruption, or discontinuation were also reported. No TEAE-related deaths occurred in either arm.
The most common TEAEs were stomatitis and nausea, mostly grade 1 or 2. One patient in each cohort experienced grade 3 adjudicated drug-related interstitial lung disease. Ocular surface events were observed in 40% of ovarian cancer patients and 27.5% of endometrial cancer patients.
Expert Commentary
"Dato-DXd monotherapy demonstrated encouraging efficacy in patients with advanced/metastatic ovarian cancer and prior platinum chemotherapy," said Ana Oaknin, MD, head of the Gynaecological Tumour Unit and Clinical Investigator of the Gynaecological Cancer Research programme at the Vall d’Hebrón Institute of Oncology in Barcelona, Spain.
Study Design
Patients in both arms received Dato-DXd at 6 mg/kg intravenously every 3 weeks. The primary study endpoints were investigator-assessed ORR and safety/tolerability. Secondary endpoints included PFS, DOR, and DCR. The ovarian cancer arm included patients with a median age of 61 years, while the endometrial cancer arm had a median age of 66.5 years. A key difference was that most ovarian cancer patients had received two or more prior treatment lines, while most endometrial cancer patients had only one prior treatment line.
Dato-DXd is also being evaluated in other tumor types, including gastric, prostate, colorectal, urothelial, and biliary tract cancers, within the TROPION-PanTumor03 study.
