Abstract PS08-08: Updated efficacy and safety of SKB264 (MK-2870) for previously treated metastatic triple negative breast cancer (mTNBC) in Phase 2 study

Abstract Background: Patients (pts) with mTNBC have limited treatment options and poor prognosis. The estimated median overall survival (OS) of pts with mTNBC is 12 to 18 months (mo) after diagnosis. SKB264, an antibody drug conjugate (ADC) composed of an anti-TROP2 antibody coupled to a cytotoxic belotecan-derivative via a novel linker with an average Drug to Antibody Ratio (DAR) of 7.4, has shown promising anti-tumor activity and tolerable safety profile in pts with mTNBC (Yin, Y. et al. SABCS 2022). Here, we report the updated data from a Phase 2 expansion cohort for pts with mTNBC (NCT04152499). Methods: Pts with previously treated mTNBC were enrolled to receive SKB264 at 4 mg/kg Q2W or 5 mg/kg Q2W in a non-randomized manner until disease progression or unacceptable toxicity. Tumor assessment was performed every 8 weeks per RECIST v1.1 assessed by investigator. The primary objective was to assess objective response rate (ORR). Secondary objectives included DoR, PFS, and OS. The TROP2 expression was scored using the semi-quantitative H-score method, and a preliminary cutoff was set as 200. TROP2 expression and its association with anti-tumor activity were retrospectively analyzed. Results: At data cut-off date (May 05, 2023), 59 pts were enrolled (23 in 4 mg/kg, 36 in 5 mg/kg), and 88% (52 pts) had received ≥3 prior lines of therapy for metastatic disease. The median follow-up was 22.8 months (mo; 95% CI, 21.3-25.2). The ORR was 42.4% (25/59, 22 confirmed and 3 unconfirmed) and disease control rate (DCR) was 76.3% (45/59). The median duration of response (DoR) was 11.5 mo (range, 3.7 to 22.1+). Median PFS (mPFS) was 5.7 mo (95% Cl: 3.8, 9.1). Median OS (mOS) was 16.8 mo (95% Cl: 12.7, NE), while 12-mo and 24-mo OS rates were 65.0% and 39.5%, respectively. In the subset of pts with high TROP2 expression (H-score>200, N=32), ORR was 53.1% (including 3 complete response), mDoR was 11.1 mo (range, 3.7 to 22.1+), mPFS was 5.8 mo (95% Cl: 3.7, 13.3), mOS was not reached (95% Cl: 9.7, NE), while 12-mo and 24-mo OS rates were 65.3% and 57.3%, respectively. Treatment-related adverse events (TRAEs) of ≥ Grade 3 severity were reported in 57.6% (34/59) of pts. The most common ≥ Grade 3 TRAEs (≥ 10%) were neutrophil count decreased (25.4%), white blood cell count decreased (23.7%), anemia (22.0%) and platelet count decreased (16.9%). TRAEs leading to dose reduction and dose delay occurred in 13.6% (8/59) and 47.5% (28/59) of pts, respectively. Three pts discontinued treatment due to TRAEs (platelet count decreased, dry eye, anaphylactic shock). No cases of interstitial lung disease (ILD), neuropathy or grade ≥3 diarrhea were observed. Serious TRAEs were reported in 28.8% (17/59) of pts; no deaths associated with TRAEs were observed. Conclusions: The updated data continues to demonstrate that pts with heavily pretreated mTNBC could achieve durable response and a trend of long-term OS benefit from SKB264 treatment, along with a manageable safety profile. Higher response rate was seen in mTNBC pts with high TROP2 expression. A Phase 3 study of SKB264 vs. investigator’s choice of chemotherapy in 3L+ mTNBC (NCT05347134) and a Phase 2 study evaluating SKB264 as monotherapy or combination with anti-PD-L1 antibody in first-line setting (NCT05445908) are ongoing in China. Citation Format: Yongmei Yin, Xinhong Wu, Quchang Ouyang, Min Yan, Lihua Song, YunPeng Liu, Zhongsheng Tong, Cuizhi Geng, Ying Wang, Guohua Yu, Xiang Wang, Ying Cheng, Weihong Zhao, Xiaoping Jin, Yina Diao, Gesha Liu, Mengyu Yang, Yue Yang, Yalan Yang, Lian Lu, Junyou Ge, Jin Li, Qun Li. Updated efficacy and safety of SKB264 (MK-2870) for previously treated metastatic triple negative breast cancer (mTNBC) in Phase 2 study [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PS08-08.