Pooled safety analysis of sacituzumab govitecan (SG) in multiple solid tumor types.

3029 Background: SG is an antibody-drug conjugate targeted to Trop-2 that received approval for treatment of previously treated metastatic triple negative breast cancer (mTNBC) and HR+/HER2- mBC in multiple countries and accelerated approval for previously treated metastatic urothelial cancer (mUC) in the US. In multiple clinical trials, SG has demonstrated significantly improved efficacy compared to standard of care therapies and a consistent, manageable safety profile with limited treatment discontinuations from adverse events (AEs). We present an analysis of pooled safety data from patients (pts) treated with SG in clinical trials, including differences by UGT1A1 polymorphisms. Methods: Safety data for pts treated with SG (10 mg/kg, days 1 and 8 every 21-day cycle) were pooled from 4 clinical trials of multiple solid tumors, including mTNBC, HR+/HER2- mBC, and mUC: ASCENT (NCT02574455), TROPiCS-02 (NCT03901339), TROPHY-U-01 (NCT03547973), and IMMU-132-01 (NCT01631552). Treatment-emergent AEs (TEAEs) were defined as any AE that started on or after first dose date until ≤ 30 days after last dose date. Results: The pooled analysis included 1063 pts; > 99% experienced any-grade TEAEs, and 76% experienced grade ≥ 3 TEAEs (Table). The most common any-grade TEAEs were nausea (64%), diarrhea (64%), neutropenia (61%), and fatigue (51%). The most common grade ≥ 3 TEAEs were neutropenia (46%), anemia (12%), leukopenia (11%), and diarrhea (11%). Febrile neutropenia occurred in 6% of pts (both any-grade and grade ≥ 3). TEAEs led to SG dose reduction in 31% and SG discontinuation in 7% of pts. The most common TEAEs that led to discontinuation were neutropenia, diarrhea, pneumonia, and fatigue (1% each). In pts with available UGT1A1 genotypes, *28/*28 was associated with a higher rate of grade ≥ 3 TEAEs and TEAEs leading to dose reduction and SG interruption compared to *1/*1 and *1/*28 (Table). Conclusions: The results of the pooled safety analysis of pts treated with SG were consistent with previous clinical trials, with neutropenia remaining the most common grade ≥ 3 TEAE. Neutropenia and diarrhea were generally manageable, and the rate of TEAEs leading to discontinuation was low. The *28/*28 UGT1A1 genotype was associated with higher rates of grade ≥ 3 TEAEs, as previously observed. This is the largest SG safety analysis published to date, providing further support for SG as a treatment with a consistent and manageable safety profile. Clinical trial information: NCT02574455 , NCT03901339 , NCT03547973 , NCT01631552 . Table: see text