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Sacituzumab tirumotecan in previously treated metastatic triple-negative breast cancer: a randomized phase 3 trial

Nature Medicine volume 31, pages 1969–1975 (2025)Cite this article

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Abstract

Chemotherapy remains a standard treatment option for metastatic triple-negative breast cancer (TNBC) but is associated with limited survival. Although some targeted antibody–drug conjugates have demonstrated clinical benefits and are considered standard therapy, persistent unmet medical needs remain due to varying accessibility. The OptiTROP-Breast01 phase 3 trial assessed sacituzumab tirumotecan (sac-TMT) versus chemotherapy in patients with locally recurrent or metastatic TNBC who had received two or more prior therapies, including at least one for metastatic disease. Patients were randomized to sac-TMT (n = 130) or chemotherapy (n = 133). The primary endpoint of progression-free survival (PFS) by blinded independent central review (BICR) was met based on the protocol-specified interim analysis. At final analysis, the median PFS by BICR was 6.7 (95% confidence interval (CI), 5.5–8.0) months with sac-TMT and 2.5 (95% CI, 1.7–2.7) months with chemotherapy (hazard ratio (HR), 0.32; 95% CI, 0.24–0.44; P < 0.00001). Concurrently, at the protocol-specified interim analysis for overall survival (OS), the median OS was not reached (95% CI, 11.2 months to not estimable (NE)) with sac-TMT and 9.4 (95% CI, 8.5–11.7) months with chemotherapy (HR, 0.53; 95% CI, 0.36–0.78; P = 0.0005). The percentage of patients with an objective response was 45.4% with sac-TMT and 12.0% with chemotherapy. The median duration of response was 7.1 (95% CI, 5.6–NE) months with sac-TMT and 3.0 (95% CI, 2.5–NE) months with chemotherapy. The most common treatment-related adverse event with sac-TMT was hematologic toxicity. Sac-TMT demonstrated statistically significant and clinically meaningful improvements in PFS compared to chemotherapy, with a manageable safety profile. The study findings support sac-TMT as an additional effective treatment option for pretreated metastatic TNBC. ClinicalTrials.gov identifier: NCT05347134.

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Fig. 1: Patient flow diagram.
Fig. 2: Kaplan–Meier curves for PFS and OS.
Fig. 3: Forest plot of PFS (per BICR) in key patient subgroups.

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Data availability

To protect the privacy of study participants and proprietary information, the sponsor shares anonymized individual patient data upon reasonable request or as required by law or regulation with qualified external researchers based on submitted curriculum vitae and reflecting non-conflict of interest. The data provided include demographic, efficacy and safety information. Approval of such requests is at the sponsor’s discretion and depends on the nature of the request, the merit of the research proposed, the availability of the data and the intended use of the data. Data requests should be sent to mict@kelun.com. In response to the inquiry, the timeframe for responding to requests is approximately 2 weeks. The redacted version of the trial protocol and statistical analysis plan is in the supplementary documents.

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Acknowledgements

We thank the patients who volunteered to participate in the OptiTROP-Breast01 study and their families for their valuable contribution and commitment as well as the dedicated clinical trial investigators and their devoted team members for participating in the OptiTROP-Breast01 study. This study was funded by Sichuan Kelun-Biotech Biopharmaceutical Co., Ltd. and was partly supported by the CAMS Innovation Fund for Medical Sciences (CIFMS; 2021-I2M-1-014 received by B.X. and 2023-I2M-C & T-B-077 received by Y.F.) and by Major Project of Medical Oncology Key Foundation of Cancer Hospital Chinese Academy of Medical Sciences CICAMS-MOMP202203 (received by Y.F.). Sichuan Kelun-Biotech Biopharmaceutical Co., Ltd. participated in study conception and design, data analysis, data interpretation, drafting or revising the paper and approval of the final version of the paper.

Author information

Author notes

  1. These authors contributed equally: Yongmei Yin, Ying Fan, Quchang Ouyang.

Authors and Affiliations

  1. Department of Oncology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China

    Yongmei Yin

  2. National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China

    Ying Fan & Binghe Xu

  3. Hunan Cancer Hospital, Changsha, China

    Quchang Ouyang

  4. Shandong Cancer Hospital, Jinan, China

    Lihua Song

  5. Zhejiang Cancer Hospital, Hangzhou, China

    Xiaojia Wang

  6. The First Hospital of Jilin University, Changchun, China

    Wei Li

  7. The Second Hospital of Dalian Medical University, Dalian, China

    Man Li

  8. West China Hospital of Sichuan University, Chengdu, China

    Xi Yan

  9. Sun Yat-sen University Cancer Center, Guangzhou, China

    Shusen Wang

  10. Cancer Hospital of China Medical University, Liaoning Cancer Hospital, Shenyang, China

    Tao Sun

  11. The First Hospital of China Medical University, Shenyang, China

    Yuee Teng

  12. Chongqing University Cancer Hospital, Chongqing, China

    Xianjun Tang

  13. Tianjin Medical University Cancer Institute & Hospital, Tianjin, China

    Zhongsheng Tong

  14. Jiangxi Cancer Hospital, Nanchang, China

    Zhengkui Sun

  15. Sichuan Kelun-Biotech Biopharmaceutical Co., Ltd., Chengdu, China

    Junyou Ge, Xiaoping Jin, Yina Diao & Gesha Liu

  16. National Engineering Research Center of Targeted Biologics, Chengdu, China

    Junyou Ge

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Contributions

Conception and design: B.X., X.J. and Y.D. Provision of study materials or patients: B.X., Y.Y., Y.F., Q.O., L.S., X.W., W.L., M.L., X.Y., S.W., T.S., Y.T., X.T., Z.T. and Z.S. Collection and assembly of data: B.X., Y.Y., Y.F., Q.O., L.S., X.W., W.L., M.L., X.Y., S.W., T.S., Y.T., X.T., Z.T. and Z.S. Data analysis and interpretation: B.X., Y.Y., J.G., X.J., Y.D. and G.L. Writing, review and editing of the paper: all authors. Final approval of the paper: all authors. Accountable for all aspects of the work: all authors.

Corresponding author

Correspondence to Binghe Xu.

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Competing interests

B.X. has served as advisor or consultant for Novartis and AstraZeneca. J.G., X.J., Y.D. and G.L. are employees of Sichuan Kelun-Biotech Biopharmaceutical Co., Ltd. The other authors declare no competing interests.

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Nature Medicine thanks Min Yan and the other, anonymous, reviewer(s) for their contribution to the peer review of this work. Primary Handling Editor: Ulrike Harjes, in collaboration with the Nature Medicine team.

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Extended data

Extended Data Fig. 1 Kaplan-Meier Curves for PFS by BICR Assessment (Interim Analysis).

Data cutoff: June 21, 2023; the protocol-specified interim analysis of PFS. The 95% CI of median PFS was determined using the Brookmeyer and Crowley method with log-log transformation. HR along with 95% CI was estimated by a stratified Cox proportional hazards model. The P value was calculated by a stratified log-rank test. The multiplicity-adjusted, one-sided alpha at this interim analysis (determined using the Lan-DeMets O’Brien-Fleming spending function) was 0.0104. The exact one-sided P value was 2.0 × 10−11. BICR, blinded independent central review; CI, confidence interval; HR, hazard ratio; PFS, progression-free survival; sac-TMT, sacituzumab tirumotecan.

Extended Data Fig. 2 Kaplan-Meier Curves for PFS by Investigator Assessment (Interim Analysis).

Data cutoff: June 21, 2023; the protocol-specified interim analysis of PFS. The 95% CI of median PFS was determined using the Brookmeyer and Crowley method with log-log transformation. HR along with 95% CI was estimated by a stratified Cox proportional hazards model. The P value was calculated by a stratified log-rank test. The exact one-sided P value was 4.0 × 10−11. CI, confidence interval; HR, hazard ratio; PFS, progression-free survival; sac-TMT, sacituzumab tirumotecan.

Extended Data Fig. 3 Kaplan-Meier Curves for PFS by Investigator Assessment (Final Analysis).

Data cutoff: November 30, 2023; the protocol-specified final analysis of PFS. The 95% CI of median PFS was determined using the Brookmeyer and Crowley method with log-log transformation. HR along with 95% CI was estimated by a stratified Cox proportional hazards model. The P value was calculated by a stratified log-rank test. The exact one-sided P value was 2.9 × 10−14. CI, confidence interval; HR, hazard ratio; PFS, progression-free survival; sac-TMT, sacituzumab tirumotecan.

Extended Data Fig. 4 Forest Plot of PFS (per Investigator Assessment) in Key Patient Subgroups.

Data cutoff: November 30, 2023; the protocol-specified final analysis of PFS. Statistical analysis was not performed when the number of patients in the subgroup was less than 10% of the total patients. HRs along with 95% CIs were estimated using an unstratified Cox proportional hazards model in each subgroup. CI, confidence interval; ECOG, Eastern Cooperative Oncology Group; HER2, human epidermal growth factor receptor 2; HR, hazard ratio; NE, not estimable; PD-1: programmed death-1; PD-L1: programmed death-ligand 1; PFS, progression-free survival; sac-TMT, sacituzumab tirumotecan; TNBC, triple-negative breast cancer.

Extended Data Fig. 5 Forest Plot of OS in Key Patient Subgroups.

Data cutoff: November 30, 2023; the protocol-specified interim analysis of OS. Statistical analysis was not performed when the number of patients in the subgroup was less than 10% of the total patients. HRs along with 95% CIs were estimated using an unstratified Cox proportional hazards model in each subgroup. CI, confidence interval; ECOG, Eastern Cooperative Oncology Group; HER2, human epidermal growth factor receptor 2; HR, hazard ratio; NE, not estimable; NR, not reached; OS, overall survival; PD-1: programmed death-1; PD-L1: programmed death-ligand 1; sac-TMT, sacituzumab tirumotecan; TNBC, triple-negative breast cancer.

Extended Data Fig. 6 Best Change in Target Lesions by BICR.

Data cutoff: November 30, 2023. BICR, blinded independent central review; IQR, interquartile range; sac-TMT, sacituzumab tirumotecan.

Extended Data Fig. 7 Overall Response (per BICR) by TROP2 Expression.

Data cutoff: November 30, 2023. BICR, blinded independent central review; Chemo, chemotherapy; ORR, objective response rate; sac-TMT, sacituzumab tirumotecan; TROP2, trophoblast cell surface antigen 2.

Extended Data Table 1 Tumor response by BICR
Full size table
Extended Data Table 2 Tumor response by investigator assessment
Full size table
Extended Data Table 3 Exploratory efficacy analysis by TROP2 expression
Full size table

Supplementary information

Supplementary Information (download PDF )

Supplementary Tables 1–4, Figs. 1 and 2, study protocol and statistical analysis plan.

Reporting Summary (download PDF )

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Yin, Y., Fan, Y., Ouyang, Q. et al. Sacituzumab tirumotecan in previously treated metastatic triple-negative breast cancer: a randomized phase 3 trial. Nat Med 31, 1969–1975 (2025). https://doi.org/10.1038/s41591-025-03630-w

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