Phase 1 Study of DS-8201a and Olaparib Combination for Treating HER2-Positive or HER2-Expressing Advanced Cancers and Platinum-Resistant Ovarian Cancer

What this Trial Is About

Researchers are studying the combination of trastuzumab deruxtecan DS-8201a and olaparib in patients with HER2-expressing cancers that have spread or cannot be removed by surgery, including platinum-resistant ovarian cancer. This phase I trial aims to find the best dose and identify side effects of this drug combination. Olaparib blocks an enzyme involved in DNA repair, potentially preventing tumor cells from repairing damage, while DS-8201a targets HER2-positive tumor cells to deliver chemotherapy directly to them. Participants receive trastuzumab deruxtecan through an intravenous infusion lasting 30 to 90 minutes on day 1 of each 21-day cycle. Olaparib is taken orally twice daily on specific days within each cycle, with cycles repeating every 21 days unless the disease progresses or unacceptable side effects occur. The study includes a dose-escalation phase followed by a dose-expansion phase for patients with platinum-resistant ovarian cancer. Throughout the trial, patients undergo various procedures including blood sample collection, heart function tests echocardiography or MUGA scan, CT scans, and biopsies. During the study, participants are closely monitored for safety and response to treatment. Researchers assess the maximum tolerated dose and record adverse events up to 30 days after treatment ends. They also measure tumor response, progression-free survival, and duration of response. Additional analyses include HER2 expression testing, pharmacokinetics, DNA damage markers, and exploratory biomarker studies using tumor and blood samples. After completing treatment, participants are followed for 30 days to monitor safety.

Testing the Combination of DS-8201a and Olaparib in HER2-Expressing Cancers With Expansion in Patients With Platinum Resistant Ovarian Cancer