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.
Yongmei Yin, Quchang Ouyang, Min Yan, Jian Zhang, Lihua Song, Wěi Li, Yuanting Gu, Xiaoyu Liu, Jingfen Wang, Xiaojia Wang, Xi Yan, Yang Jin, Weipeng Zhao, Yuee Teng, Tingjing Yao, Zhengkui Sun, Xiaoping Jin, Yina Diao, Gesha Liu, Junyou Ge
Abstract
1019 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 first-line 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 (NCT06279364). Clinical trial information: NCT05445908 .