Abstract CT038: Preliminary efficacy and safety results of anti-TROP2 ADC SKB264 (MK-2870) in patients (pts) with previously treated advanced gastric (G) or gastroesophageal junction (GEJ) cancer from a Phase 2 study

Abstract Background: Overexpression of TROP2 (trophoblast cell surface antigen 2) in advanced gastric cancer is known as a poor prognostic factor. SKB264 (MK-2870) is a TROP2 ADC developed with a novel linker to conjugate the payload, a belotecan-derivative topoisomerase I inhibitor. The linker is affected by both extracellular pH-sensitive cleavage and intracellular enzymatic cleavage within tumor cells, which leads to efficiently release payload inside tumor cells as well as within tumor microenvironment to exert its anti-tumor effects. Here, we report the preliminary results from a Phase 2 expansion cohort in pts with advanced G/GEJ cancer. Methods: Pts with previously treated inoperable advanced G/GEJ adenocarcinoma were enrolled to receive SKB264 monotherapy at 5 mg/kg Q2W until disease progression or unacceptable toxicity in Phase 2 expansion cohort of KL264-01 study (NCT04152499). Pts with heavily pre-treated G/GEJ cancer were enrolled first, and then the cohort was amended to enroll pts with only one prior therapy of chemotherapy and anti-PD-1/L1 therapy. Tumor assessment was performed every 8 weeks per RECIST v1. 1 assessed by investigator. Results: At data cutoff date (Nov 22, 2023), a total of 48 pts were enrolled and followed up for at least 9 weeks. 24 pts (50. 0%) had received one prior line of therapy (2L), while 24 pts (50. 0%) had received ≥ 2 prior lines of therapy (3L+). 40 pts (83. 3%) had received prior anti-PD-1/L1 inhibitors. Treatment-related adverse events (TRAEs) of ≥ Grade 3 were reported in 52. 1% of pts. The most common ≥ Grade 3 TRAEs (occurred in ≥5% of pts) were anemia (20. 8%), neutrophil count decreased (18. 8%), WBC decreased (12. 5%) and neutropenia (6. 3%). TRAEs leading to dose reduction and dose delay occurred in 18. 8% and 33. 3% of pts, respectively. No TRAEs leading to treatment discontinuation or deaths occurred. No neuropathy or drug-related ILD/pneumonitis was reported. Of 41 response-evaluable pts (defined as ≥ 1 on-study scans), the ORR was 22. 0% (9 PRs, 2 pending confirmation) and disease control rate (DCR) was 80. 5%. The ORRs in the 2L and 3L+ setting were 27. 3% (including 2 pending confirmation) and 15. 8%, respectively. Median duration of response (DoR) was 7. 5 months (mos). In the subset of 3L+ pts (n=24 including 54. 2% of pts with ≥ 4 prior lines of therapy) with more mature follow-up (median follow up of 14. 6 mos), median progression free survival (mPFS) was 3. 7 mos (95% Cl: 2. 6, 5. 4) ; median overall survival (mOS) was 7. 6 mos (95% Cl: 5. 3, 15. 5) with 12-mo OS rate of 32. 6%. Conclusions: The preliminary data suggests that pts with heavily pre-treated advanced G/GEJ cancer could achieve durable response and potentially prolonged OS from SKB264 monotherapy, with a manageable safety profile. A Phase 3 global study of SKB264 monotherapy vs SOC in 3L+ G/GEJ adenocarcinoma is being planned. Citation Format: Jordi Rodon, Zev A. Wainberg, Mingjun Zhang, Tianshu Liu, Bo Liu, Guohua Yu, Yongmei Yin, Shuang Zhang, Yanjun Mi, Xingya Li, Xian Wang, Yunpeng Liu, Xiang Wang, Ying Cheng, Xiaoqing Zhang, Yalan Yang, Junyou Ge, Omobolaji O. Akala, Elliot Chartash, Jin Li. Preliminary efficacy and safety results of anti-TROP2 ADC SKB264 (MK-2870) in patients (pts) with previously treated advanced gastric (G) or gastroesophageal junction (GEJ) cancer from a Phase 2 study abstract. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts) ; 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84 (7Suppl): Abstract nr CT038.