KEY TAKEAWAYS
- An interventional phase I/II trial aimed to evaluate the safety and efficacy of tinostamustine in OvCa.
- Tinostamustine shows early promise for OvCa with acceptable side effects.
Tinostamustine, an innovative deacetylase inhibitor with alkylating properties, enhances accessibility to cancer cell DNA strands, inducing breaks and impeding damage repair. Anna V Tinker and her research group aimed to assess the safety and effectiveness of tinostamustine in a subgroup of ovarian cancer (OvCa) patients (pts) participating in a Phase I/II clinical trial.
The study included pts aged ≥18 years with advanced solid tumors, life expectancy >3 months, and Eastern Cooperative Oncology Group performance status (ECOG-PS) ≤2, and tinostamustine was administered to them.
The phase I study employed a standard 3+3 design, escalating doses from 60 to 100 mg/m2, defining the maximum tolerated dose(MTD) and RP2D. In Phase II, the objective response rate(ORR) (complete response [CR] + partial response [PR]) and the rate of pts. With stable disease (SD) ≥4 months following RP2D (80 mg2 over 60 minutes on Days 1 and 15 of each 4-week cycle) were assessed and described using descriptive statistics. Two substudies examined the impact of tinostamustine (60–80 mg/m2) on cardiac repolarization.
Around 49 pts. with advanced solid tumors (including 18 with OvCa) were enrolled in the trial. Phase I observed no dose-limiting toxicities in the entire population. In Phase II, treatment-related adverse events (TEAEs) related to tinostamustine were predominantly hematological or gastrointestinal. Serious tinostamustine-related AEs were primarily hematological. In the OvCa subset, a higher proportion experienced tinostamustine-related TEAEs and serious AEs than the overall population. Only 1 OvCa patient had a fatal AE of intra-abdominal hemorrhage with Grade 4 hematological AEs, all linked to tinostamustine. Among OvCa pts., 1/18 achieved CR, 1/18 PR, and 7/18 stable disease ≥4 months. Of 10 pts discontinued treatment due to progressive disease.
The study concluded that tinostamustine exhibited promising indicators of efficacy accompanied by well-managed tolerability in pts. diagnosed with OvCa. This study was sponsored by Mundipharma Research Limited.
Source: https://www.emma.events/site/programme/?sessiondetail=4534565&trackid=0&a=esgo2023#!
Clinical trial: https://clinicaltrials.gov/study/NCT03345485
Tinker AV, Chugh R, Curigliano G, et al. “Results From A Phase I/II Trial Of Tinostamustine Monotherapy In Advanced Solid Tumours (NCT03345485): Safety And Efficacy In A Subset Of Patients With Advanced Ovarian Cancer (OvCa)” Presented at ESGO Congress 2023. (Abstract #163)
