Sacituzumab govitecan plus toripalimab compared with toripalimab plus nab-paclitaxel for first-line treatment of unresectable, locally advanced, or metastatic triple-negative breast cancer: protocol of a multicenter, open-label, randomized phase II trial
5 affiliations
- 1Senior Department of Oncology, The Fifth Medical Center of Chinese PLA General Hospital, Beijing, China
- 2Department of Oncology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China
- 3Department of Oncology, The First Hospital of Lanzhou University, Lanzhou, China
- 4Breast Disease Department, Peking University Shougang Hospital, Beijing, China
- 5Department of Medical Oncology, The Second Hospital of Dalian Medical University, Dalian, China
Abstract
Background: First-line therapeutic landscape for advanced triple-negative breast cancer (TNBC) has evolved significantly following recent phase III studies. In the TORCHLIGHT trial, toripalimab plus nab-paclitaxel improved progression-free survival (PFS) versus placebo combined with nab-paclitaxel in programmed death ligand 1 (PD-L1)-positive disease. In ASCENT-03, sacituzumab govitecan monotherapy demonstrated longer PFS than chemotherapy among untreated patients with advanced TNBC who were ineligible for anti-programmed cell death protein 1 (PD-1)/PD-L1 treatment. ASCENT-04/KEYNOTE-D19 reported a significant reduction in the risk of disease progression or death for sacituzumab govitecan plus pembrolizumab compared to chemotherapy plus pembrolizumab in patients with PD-L1-positive tumor. However, prospective evidence for sacituzumab govitecan plus toripalimab is lacking in a China-relevant PD-L1-positive population.
Methods: This multicenter, open-label, randomized, exploratory superiority, parallel-group phase II trial (NCT07040644; protocol CO-US-979-7331) enrolls patients with treatment-naïve unresectable locally advanced or metastatic PD-L1-positive TNBC. Patients are randomly assigned in equal proportions to receive either sacituzumab govitecan at 10 mg/kg intravenously (IV; days 1 and 8) plus toripalimab at 240 mg IV (day 1) or toripalimab at 240 mg IV (day 1) plus nab-paclitaxel at 125 mg/m2 IV (day 1 and 8) in a 3-week cycle. Primary endpoint is PFS assessed by investigators per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. Key secondary and exploratory endpoints encompass objective response rate (ORR), duration of response (DoR), time to response (TTR), overall survival (OS), safety, and subgroup analyses, including visceral metastasis status, prior curative-setting anti-PD-(L)1 exposure, disease status, disease-free interval (DFI), and prior taxane therapy, among others.
Discussion: This phase II trial is designed to evaluate the superiority of sacituzumab govitecan plus toripalimab over toripalimab plus nab-paclitaxel in a treatment setting relevant to Chinese practice. Notable design features include enrollment in China, use of toripalimab as the locally approved immune checkpoint inhibitor partner, inclusion of a broader PD-L1-positive population, and allowance for prior immune checkpoint inhibitor exposure in the curative setting. This trial may clarify the role of sacituzumab govitecan plus toripalimab in first-line PD-L1-positive advanced TNBC in China.
Trial Registration: ClinicalTrials.gov, NCT07040644; URL: https://clinicaltrials.gov/study/NCT07040644
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BibTeX
@article{zhang2026sacituzumab,
title = {{Sacituzumab govitecan plus toripalimab compared with toripalimab plus nab-paclitaxel for first-line treatment of unresectable, locally advanced, or metastatic triple-negative breast cancer: protocol of a multicenter, open-label, randomized phase II trial}},
author = {Shaohua Zhang and Jianli Zhao and Xiaoling Ling and Xueli Mo and Man Li and Herui Yao and Zefei Jiang},
journal = {Translational Breast Cancer Research},
year = {2026},
month = oct,
doi = {10.21037/tbcr-2026-0056},
url = {https://doi.org/10.21037/tbcr-2026-0056},
note = {CC BY-NC-ND 4.0},
}
RIS
TY - JOUR
TI - Sacituzumab govitecan plus toripalimab compared with toripalimab plus nab-paclitaxel for first-line treatment of unresectable, locally advanced, or metastatic triple-negative breast cancer: protocol of a multicenter, open-label, randomized phase II trial
AU - Shaohua Zhang
AU - Jianli Zhao
AU - Xiaoling Ling
AU - Xueli Mo
AU - Man Li
AU - Herui Yao
AU - Zefei Jiang
PY - 2026
DA - 2026/10/15
JO - Translational Breast Cancer Research
DO - 10.21037/tbcr-2026-0056
UR - https://doi.org/10.21037/tbcr-2026-0056
AB - Background: First-line therapeutic landscape for advanced triple-negative breast cancer (TNBC) has evolved significantly following recent phase III studies. In the TORCHLIGHT trial, toripalimab plus nab-paclitaxel improved progression-free survival (PFS) versus placebo combined with nab-paclitaxel in programmed death ligand 1 (PD-L1)-positive disease. In ASCENT-03, sacituzumab govitecan monotherapy demonstrated longer PFS than chemotherapy among untreated patients with advanced TNBC who were ineligible for anti-programmed cell death protein 1 (PD-1)/PD-L1 treatment. ASCENT-04/KEYNOTE-D19 reported a significant reduction in the risk of disease progression or death for sacituzumab govitecan plus pembrolizumab compared to chemotherapy plus pembrolizumab in patients with PD-L1-positive tumor. However, prospective evidence for sacituzumab govitecan plus toripalimab is lacking in a China-relevant PD-L1-positive population. Methods: This multicenter, open-label, randomized, exploratory superiority, parallel-group phase II trial (NCT07040644; protocol CO-US-979-7331) enrolls patients with treatment-naïve unresectable locally advanced or metastatic PD-L1-positive TNBC. Patients are randomly assigned in equal proportions to receive either sacituzumab govitecan at 10 mg/kg intravenously (IV; days 1 and 8) plus toripalimab at 240 mg IV (day 1) or toripalimab at 240 mg IV (day 1) plus nab-paclitaxel at 125 mg/m2 IV (day 1 and 8) in a 3-week cycle. Primary endpoint is PFS assessed by investigators per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. Key secondary and exploratory endpoints encompass objective response rate (ORR), duration of response (DoR), time to response (TTR), overall survival (OS), safety, and subgroup analyses, including visceral metastasis status, prior curative-setting anti-PD-(L)1 exposure, disease status, disease-free interval (DFI), and prior taxane therapy, among others. Discussion: This phase II trial is designed to evaluate the superiority of sacituzumab govitecan plus toripalimab over toripalimab plus nab-paclitaxel in a treatment setting relevant to Chinese practice. Notable design features include enrollment in China, use of toripalimab as the locally approved immune checkpoint inhibitor partner, inclusion of a broader PD-L1-positive population, and allowance for prior immune checkpoint inhibitor exposure in the curative setting. This trial may clarify the role of sacituzumab govitecan plus toripalimab in first-line PD-L1-positive advanced TNBC in China. Trial Registration: ClinicalTrials.gov, NCT07040644; URL: https://clinicaltrials.gov/study/NCT07040644
SN - 2218-6778
ER -