Related Experiment Video
Updated: Jan 8, 2026
Endobronchial Ultrasound-guided Intratumoral Injection of Cisplatin for the Treatment of Isolated Mediastinal Recurrence of Lung Cancer
Published on: February 12, 2017
A phase II, multicenter, open-label, single-arm study of berzosertib plus topotecan in patients with relapsed
A Navarro1, A Thomas2, Y Cheng3
1Department of Medical Oncology, University Hospital Vall d'Hebron, Barcelona, Spain.
Background:
Small-cell lung cancer (SCLC) is characterized by high genomic instability. Proteins involved in maintaining genomic stability, such as ataxia telangiectasia and Rad3-related (ATR) and topoisomerase 1, are promising therapeutic targets in SCLC. Berzosertib, a highly potent, selective, intravenously administered ATR inhibitor, has demonstrated promising antitumor activity in patients with platinum-resistant SCLC.
Materials And Methods:
This phase II, multicenter, open-label, single-arm study (NCT04768296) included patients with relapsed platinum-resistant SCLC who received berzosertib (210 mg/m2 on days 2, 5) and topotecan (1.25 mg/m2 on days 1-5) intravenously in 21-day cycles until disease progression. Primary endpoints were objective response rate (ORR per RECIST v1.1), assessed by an Independent Review Committee. Key secondary endpoints included progression-free survival (PFS), overall survival (OS), and safety.
Results:
A preplanned interim analysis for futility after the first 40 patients had completed their second on-treatment tumor assessment (or dropped out/died prematurely) revealed a low probability of reaching the predefined efficacy threshold, leading to premature study termination. At the final analysis (n = 73), four patients achieved confirmed partial response, resulting in an ORR of 5.5%. The median PFS was 2.2 months [95% confidence interval (CI) 1.5-2.7 months], and the median OS was 6.4 months (95% CI 4.2-7.6 months). No new safety concerns were observed, with the safety profile of berzosertib and topotecan combination therapy being consistent with the known risk profile of the respective monotherapies.
Conclusions:
No added clinical benefit of berzosertib and topotecan combination was observed over topotecan monotherapy in patients with platinum-resistant SCLC.
Insights
Adding berzosertib to topotecan did not improve outcomes for patients with platinum-resistant small-cell lung cancer (SCLC). The combination therapy showed no added clinical benefit over topotecan alone in this patient population.
Area of Science:
- Oncology
- Genomic Instability
- Drug Development
Background:
- Small-cell lung cancer (SCLC) exhibits significant genomic instability.
- Ataxia telangiectasia and Rad3-related (ATR) inhibitors, like berzosertib, are potential therapeutic targets for SCLC.
- Berzosertib has shown prior promise in platinum-resistant SCLC.
Purpose of the Study:
- To evaluate the efficacy and safety of combining berzosertib with topotecan in patients with relapsed platinum-resistant SCLC.
- To determine if this combination offers improved outcomes compared to monotherapy.
Main Methods:
- A phase II, multicenter, open-label, single-arm study.
- Patients received intravenous berzosertib and topotecan in 21-day cycles.
- Primary endpoint was objective response rate (ORR); secondary endpoints included progression-free survival (PFS) and overall survival (OS).
Main Results:
- The study was terminated early due to a low probability of meeting efficacy thresholds.
- The objective response rate (ORR) was 5.5% (4 partial responses in 73 patients).
- Median PFS was 2.2 months and median OS was 6.4 months. Safety profile was consistent with monotherapies.
Conclusions:
- The combination of berzosertib and topotecan did not demonstrate added clinical benefit in platinum-resistant SCLC.
- No significant improvement in efficacy was observed compared to topotecan monotherapy.
- Further investigation of this combination in this setting is not warranted.
More Related Videos
03:07Single-Port Robotic-assisted Transaxillary Breast-conserving Surgery: A Prospective, Single-arm, Non-randomized Phase IIa Clinical Trial
Published on: August 19, 2025
15:04Potentiation of Anticancer Antibody Efficacy by Antineoplastic Drugs: Detection of Antibody-drug Synergism Using the Combination Index Equation
Published on: January 19, 2019
