Editor’s Note: Sacituzumab Tirumotecan (sac-TMT) is a novel TROP2-targeted ADC independently developed in China. Over the past two years, its clinical findings have been frequently presented at major international conferences and published in top-tier journals. At the 2025 ASCO Annual Meeting, Professor Yongmei Yin from Jiangsu Provincial People’s Hospital delivered a Rapid Oral Abstract presentation on the phase II OptiTROP-Breast05 study, which evaluated sac-TMT as a first-line therapy for advanced triple-negative breast cancer (TNBC). The results demonstrated impressive efficacy and a favorable safety profile. Oncology Frontier invited Professor Yongmei Yin at the conference to discuss the study's key outcomes and how sac-TMT, as a leading TROP2 ADC, is poised to make a lasting impact on breast cancer treatment in China and globally.

Tracing ASCO

• Spotlight on ASCO
• Sac-TMT Returns to the ASCO Stage as a Leading Chinese TROP2 ADC

Oncology Frontier: Congratulations on having the OptiTROP-Breast05 study selected for a Rapid Oral Abstract at ASCO. Could you share the study’s most important findings and their potential implications for clinical practice?

Professor Yongmei Yin: TNBC is widely considered the most aggressive subtype of breast cancer. Standard chemotherapy offers limited survival benefits in advanced stages, and the applicability of immune checkpoint inhibitors and PARP inhibitors is often restricted by biomarker requirements. Therefore, there is an urgent need for new therapies to address these unmet clinical needs. Sac-TMT has been under continuous investigation in advanced TNBC. From our earlier KL264-01 basket trial presented at ESMO to Academician Binghe Xu’s oral presentation of the OptiTROP-Breast01 study at last year’s ASCO, the agent has shown consistent efficacy and safety in later-line settings. It has since been approved in China and is recommended in key national guidelines, including those from CSCO-BC, CBCS & CSOBO, and ABCC.

In the OptiTROP-Breast05 phase II study, we moved sac-TMT into the first-line treatment setting. The results were highly encouraging, with an objective response rate (ORR) of 70.7%, a median duration of response (DoR) of 12.2 months, and a median progression-free survival (PFS) of 13.4 months. These numbers are comparable to what has been achieved with other TROP2 ADCs used in combination with immunotherapy or chemotherapy. Notably, the majority of enrolled patients (78.0%) were PD-L1 negative (CPS < 10), yet they demonstrated similar benefits, with an ORR of 71.9% and a median PFS of 13.1 months.

In terms of safety, the adverse event profile was manageable and consistent with previous reports. The most common grade ≥3 treatment-related adverse events included neutropenia, leukopenia, and anemia. There were no cases of neuropathy or interstitial lung disease/pneumonitis, which is reassuring. These findings support sac-TMT as a strong candidate for first-line treatment in advanced TNBC. A phase III trial (NCT06279364) is currently underway, and we are optimistic that it will confirm the phase II findings. If successful, sac-TMT could provide a new frontline option, especially for patients with PD-L1–negative and BRCA wild-type TNBC who currently face limited treatment choices.

A Global Vision for Sac-TMT

Oncology Frontier: Sac-TMT is also being studied internationally through multiple global trials. How do you see this drug shaping breast cancer care around the world?

Professor Yongmei Yin: Sac-TMT is a Chinese innovation from top to bottom. It features a fully domestically developed monoclonal antibody, a novel linker, and a payload with a methylsulfonyl modification that enhances stability in circulation. Its high drug-to-antibody ratio and strong bystander effect allow it to effectively target both TROP2-expressing and adjacent tumor cells. These design elements give sac-TMT the qualities of a globally competitive therapeutic built on Chinese scientific excellence.

Sac-TMT has attracted considerable international attention at ESMO, ASCO, and other global forums. Studies such as OptiTROP-Breast01, Breast05, and Breast02 have produced promising data in Chinese populations, covering both TNBC and HR+/HER2− metastatic breast cancer. These findings lay a strong foundation for global expansion.

Several international multicenter trials are now underway. These include MK-2870-032 and MK-2870-012 for early TNBC in the neoadjuvant and adjuvant settings, MK-2870-011 for first-line advanced TNBC, and MK-2870-010 for HR+/HER2− metastatic breast cancer. At this year’s ASCO meeting, Professor Heather McArthur from UT Southwestern presented details on the ongoing MK-2870-032 intensified adjuvant therapy study (NCT06393374). We are hopeful that these international studies will generate positive results and further position sac-TMT as a high-quality, efficient “China solution” for breast cancer treatment worldwide.

Study Overview

Study Title: Sacituzumab tirumotecan (sac-TMT) as first-line treatment for unresectable locally advanced/metastatic triple-negative breast cancer (a/mTNBC): Initial results from the phase II OptiTROP-Breast05 study.

Background:

TROP2 (trophoblast cell surface antigen 2) is highly expressed in TNBC and associated with poor survival. Sac-TMT (MK-2870/SKB264) is a TROP2 ADC developed with a novel linker to conjugate the payload, a belotecan-derivative topoisomerase I inhibitor. It is approved in China for pts with a/mTNBC who have received at least two prior chemotherapies, including one for metastatic disease. The Phase II OptiTROP-Breast05 study (NCT05445908) evaluated sac-TMT as first-line treatment for pts with a/mTNBC. The study also explored the impact of PD-L1 combined positive score (CPS) status. Pts with CPS＜10 (PD-L1-negative, IHC 22C3 pharmDx) have limited treatment options, representing a critical unmet need.

Methods:

Pts with a/mTNBC who had not received prior treatment for advanced disease were enrolled, regardless of PD-L1 or TROP2 status, to receive sac-TMT at 5 mg/kg Q2W until disease progression or unacceptable toxicity. For pts with recurrent TNBC, a disease-free interval (DFI) of at least 6 months was required for eligibility. Tumor assessment was performed every 6 weeks per RECIST v1.1 as assessed by investigator.

Results:

As of 18 Nov 2024, a total of 41 pts (median age 55 yrs; 43.9% ECOG PS 1; 78.0% PD-L1 CPS＜10) were enrolled; 61.0% of pts had visceral metastases at baseline, 29.3% of pts had de novo metastasis, 19.5% of pts had a DFI of 6-12 months (mos), and 51.2% of pts had a DFI＞12 mos.

The median follow-up was 18.6 mo. The objective response rate (ORR) was 70.7% (29/41, 3 unconfirmed PR) and the disease control rate (DCR) was 92.7%. Median duration of response (mDoR) was 12.2 mo, while the median progression-free survival (mPFS) was 13.4 mo, and the 12-mo PFS rate was 64.6% (95% CI: 45.0%, 78.7%).

Among the 32 pts with PD-L1 CPS＜10, the ORR was 71.9% (23/32, 3 unconfirmed PR) and the DCR was 93.8%. The mPFS in this subgroup was 13.1 mo, with a 12-mo PFS rate 59.1% (95% CI: 37.1%, 75.7%). Treatment-related adverse events (TRAEs) of grade 3 or higher occurred in 63.4% of pts.

The most common ≥grade 3 TRAEs (occurred in ≥5% of pts) were neutrophil count decreased (46.3%), WBC count decreased (34.1%), anemia (12.2%), stomatitis (9.8%), lymphocyte count decreased (7.3%) and fatigue (7.3%). No treatment-related deaths occurred, and there were no reports of neuropathy or interstitial lung disease/pneumonitis.

Conclusions:

Sac-TMT demonstrated promising anti-tumor activity with a manageable safety profile as a firstline treatment for pts with a/mTNBC, independent of the PD-L1 status. A Phase 3 study comparing sac-TMT vs investigator’s choice of chemotherapy in first-line PD-L1-negative (CPS＜10) a/mTNBC is currently underway.

Jiangsu Provincial People’s Hospital