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Biomarker-driven targeted therapy in patients with recurrent platinum-resistant epithelial ovarian cancer (BRIGHT):
Background:
Platinum-resistant, recurrent ovarian cancer has an abysmal prognosis with limited treatment options. Poly-(ADP-ribose)-polymerase (PARP), angiogenesis, and immune checkpoint inhibitors might improve the outcomes of platinum-resistant, recurrent ovarian cancer, but accurate patient selections for those therapies remain a significant clinical challenge.
Primary Objective:
To evaluate the efficacy and safety of biomarker-driven combinatorial therapies of pamiparib, tislelizumab, bevacizumab, and nab-paclitaxel in platinum-resistant, recurrent ovarian cancer.
Study Hypothesis:
A precision medicine combination of PARP inhibitors, anti-angiogenic therapy, immunotherapy, and chemotherapy will improve disease outcomes of platinum-resistant, recurrent ovarian cancer by accounting for genomic and immunologic features.
Trial Design:
The BRIGHT Trial is a prospective, open-label, multicenter, phase II, umbrella study planning to enroll 160 patients with serous, endometrioid, or clear cell platinum-resistant, recurrent ovarian cancer from 11 clinical centers in China. Patients are assigned to one of three experimental arms based on biomarkers. Patients with BRCA1/2 mutations will receive pamiparib plus bevacizumab (arm 1, n=40) regardless of CD8+ tumor-infiltrating lymphocytes count. Patients with wild-type BRCA1/2 (BRCAwt) and ≥3 CD8+ tumor-infiltrating lymphocytes count will receive the combination of tislelizumab, bevacizumab, and nab-paclitaxel (arm 2, n=50), while BRCAwt patients with <3 CD8+ tumor-infiltrating lymphocytes count will receive bevacizumab plus dose-dense nab-paclitaxel (arm 3, n=50). After completing patient enrollment in arm 2, another 20 BRCAwt patients with ≥3 CD8+ tumor-infiltrating lymphocytes count will be included as an arm 2 expansion. Treatment will continue until disease progression or intolerable toxicity, and all adverse events will be recorded.
Major Inclusion/Exclusion Criteria:
Eligible patients include those aged ≥18 with serous, endometrioid, or clear cell ovarian cancer, platinum-resistant recurrence, and Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
Primary Endpoint:
Objective response rate (ORR) assessed by the investigators by the RECIST 1.1 criteria.
Sample Size:
160 patients.
Estimated Dates For Completing Accrual And Presenting Results:
Recruitment is estimated to be completed by 2024 and results may be published by 2027.
Trial Registration:
ClinicalTrials.gov: NCT05044871.
Insights
This study evaluates biomarker-driven combination therapies for platinum-resistant ovarian cancer. Precision medicine approaches aim to improve outcomes by targeting specific patient genomic and immune features.
Area of Science:
- Oncology
- Genetics
- Immunology
Background:
- Platinum-resistant recurrent ovarian cancer presents a poor prognosis and limited therapeutic avenues.
- Poly-(ADP-ribose)-polymerase (PARP) inhibitors, anti-angiogenic agents, and immune checkpoint inhibitors show potential but require precise patient selection.
- Identifying optimal patient subgroups for these advanced therapies remains a critical clinical challenge.
Purpose of the Study:
- To assess the efficacy and safety of a biomarker-guided combination therapy involving pamiparib, tislelizumab, bevacizumab, and nab-paclitaxel.
- To investigate the impact of combining PARP inhibition, anti-angiogenesis, immunotherapy, and chemotherapy in platinum-resistant ovarian cancer.
- To determine if accounting for genomic (BRCA1/2 mutations) and immunologic (CD8+ tumor-infiltrating lymphocytes) features can improve disease outcomes.
Main Methods:
- The BRIGHT Trial is a prospective, open-label, multicenter Phase II umbrella study enrolling 160 patients in China.
- Patients with platinum-resistant ovarian cancer are assigned to three arms based on BRCA1/2 mutation status and CD8+ TILs count.
- Treatments include combinations of pamiparib, bevacizumab, tislelizumab, and nab-paclitaxel, continuing until disease progression or toxicity.
Main Results:
- Objective response rate (ORR) by RECIST 1.1 criteria is the primary endpoint.
- Patient enrollment is planned for 160 individuals across three experimental arms.
- Recruitment is expected to conclude by 2024, with results anticipated by 2027.
Conclusions:
- This trial hypothesizes that a precision medicine combination therapy will enhance outcomes for platinum-resistant ovarian cancer.
- The study aims to validate the efficacy of targeted therapies based on individual patient biomarkers.
- Results from the BRIGHT Trial (NCT05044871) will provide crucial insights into personalized treatment strategies.
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