| Trial ID # | NCT02595892 |
| Phase | II |
| Drug Class | DNA Damage Repair Pathway Inhibitors: ATR |
| Drug Name | Berzosertib |
| Alternate Drug Names | ATR kinase inhibitor VX-970, VE-822, M6620, VX-970 |
| Drugs in Trial | Berzosertib, Gemcitabine |
| Eligible Participant | Platinum resistant ovarian cancer |
| Patients Enrolled | 70; median 2 prior therapies (1-8) |
| Therapy Setting | Recurrence |
| Study Design | Open-Label, Randomized |
| Endpoints | PFS, OS, evaluated per RECIST |
| Biomarkers | Exploratory: PFI, Replication Stress (RS) High/Low |
| Efficacy | Ber+Gem (n=36) vs Gem (n=34): PFS: 5.7 vs 3.7 months, HR: 0.57 (0.33-0.98, p=0.044) Exploratory analysis; PFI, RS High, RS Low: RS High vs RS High Low: |
| Clinically Significant Adverse Events | Ber+Gem vs Gem: |
| Conclusion | Addition of berzosertib to gemcitabine increases PFS without additional toxicity, the benefit was observed mainly in patients with platinum-free interval less than 3 months |
| Reference | Konstatinopoulos PA et al. Berzosertib plus gemcitabine versus gemcitabine alone in platinum-resistant high-grade serous ovarian cancer: a multicentre, open-label, randomised, phase 2 trial. Lancet Oncol (2020) 21(7):957-968 https://pubmed.ncbi.nlm.nih.gov/32553118/ Konstatinopoulos PA et al. A Replication stress biomarker is associated with response to gemcitabine versus combined gemcitabine and ATR inhibitor therapy in ovarian cancer. Nat Commun (2021) 12(1):5574 Konstantinopoulos P et al. Randomized Phase II Study of Gemcitabine With or Without ATR Inhibitor Berzosertib in Platinum-Resistant Ovarian Cancer: Final Overall Survival and Biomarker Analyses. JCO Precis Oncol (2024) 8:e2300635 |