KEY TAKEAWAYS
- The phase 1 trial aimed to investigate the safety and efficacy of R-DXd in patients with previously treated OVC.
- Researchers noticed promising safety and efficacy of R-DXd in patients with heavily pretreated OVC; further investigation is ongoing.
Raludotatug deruxtecan (R-DXd) is an antibody-drug conjugate comprised of a humanized IgG1 antibody against cadherin 6 (CDH6), a stable linker selectively cleaved within tumor cells and a membrane permeable topoisomerase I inhibitor. Expression of CDH6, a cell adhesion protein, is increased in the majority of epithelial ovarian cancer (OVC) cases and is associated with poor prognosis.
In this ongoing phase 1 trial, Kathleen N. Moore and the team aimed to evaluate the efficacy and safety of R-DXd, as a first-in-human trial in previously treated patients with OVC.
Researchers performed an inclusive analysis of patients with advanced epithelial OVC who had previously undergone taxane and platinum therapies. No patient pre-selection for any biomarker was employed. Part A of the study, which involved dose escalation, assessed the tolerability of R-DXd at 1.6 to 9.6 mg/kg. Subsequently, doses of 4.8 to 8.0 mg/kg were expanded in Part B; however, the 8.0 mg/kg cohort was closed due to the emerging risk-to-benefit ratio. A subgroup analysis of patients who received R-DXd at 4.8 to 6.4 mg/kg.
About 45 patients had received R-DXd at doses ranging from 4.8 (n=13), 5.6 (n=8), and 6.4 (n=24) as of 14 July 2023. Of the majority of patients across the 3 dose groups, 40 patients (88.9%) had platinum-resistant disease, and 29 (64.4%) with a significant portion having prior exposure to bevacizumab and PARP inhibitors. The median number of prior lines of therapy was 4 (range: 1–12). At the data cut-off, 30 patients (66.7%) were still on study treatment, with a median treatment duration of 17.9 weeks (range: 3.0–114.9).
Treatment-emergent adverse events (TEAEs) were experienced by 42/45 patients (93.3%), and grade ≥3 TEAEs were reported in 44.4% of patients. The most common any-grade TEAEs were nausea (57.8%), vomiting (40.0%), fatigue (37.8%), and diarrhea (31.1%). AEs led to R-DXd discontinuation in 5 patients (11.1%). The confirmed overall response rate (ORR), as per RECIST v1.1 criteria, was 48.6% (18/37; 95% CI: 31.9–65.6), with 1 patient achieving a complete response (CR) in a patient who received R-DXd at 4.8 mg/kg. Another 18 patients (48.6%) had achieved stable disease (SD).
The disease control rate was 97.4% (95% CI: 86.2–99.9), and the clinical benefit rate (CR+PR+SD lasting ≥180 days) was 50.0% (95% CI: 33.4–66.6). The median duration of response was 11.2 months (95% CI: 3.1–not estimable [NE]), and the median progression-free survival was 8.1 months (95% CI: 5.3–NE). In addition, preliminary correlation analyses between CDH6 expression and efficacy parameters will be presented.
The study concluded that R-DXd exhibited a manageable safety profile and promising preliminary efficacy in patients with unselected, heavily pretreated OVC. These findings provide valuable support for advancing further clinical development in OVC, as evidenced by the ongoing phase 2/3 trial (NCT06161025 [REJOICE-Ovarian01]).
The trial was sponsored by the Daiichi Sankyo.
Source: https://sgo.planion.com/Web.User/AbstractDet?ACCOUNT=SGO&ABSID=579345&CONF=AM2024&CKEY=
Clinical Trial: https://clinicaltrials.gov/study/NCT04707248
Moore K.N., Philipovskiy A, Harano K, et al. (2024). “Raludotatug deruxtecan monotherapy among patients with previously treated ovarian cancer: Subgroup analysis of a first-in-human phase I study.” Presented at SGO 2024. (4)
