DS-7300 (B7-H3 DXd-ADC) in patients (pts) with metastatic castration-resistant prostate cancer (mCRPC): A subgroup analysis of a phase 1/2 multicenter study.
Authors: Patel Manish R. , Johnson Melissa Lynne , Falchook Gerald Steven , Doi Toshihiko , Friedman Claire Frances , Piha-Paul Sarina Anne , Gutierrez Martin , Shimizu Toshio , Cheng Ben , Qian Meng , Qian Xiaozhong , Myobatake Yusuke , Laadem Abderrahmane , Yoshizuka Naoto , Hammett Tracey , Kirui Julius , Arkenau Hendrik-Tobias 
Published: February 2022

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Background: DS-7300 is an antibody drug conjugate with an exatecan derivative payload that targets B7-H3, which is overexpressed in various cancers. Initial findings from an ongoing phase 1/2 dose escalation study for advanced solid tumors, and dose-expansion studies in esophageal squamous cell carcinoma and mCRPC (NCT04145622) showed that DS-7300 was generally well tolerated with early signs of clinical activity (ESMO 2021, abstract 513O). Here, we present preliminary results from the mCRPC pt subset. Methods: This study consisted of 2 parts: dose- escalation (part 1) and expansion (part 2). Part 1 assessed the safety and tolerability of DS-7300 with doses ranging from 0.8 to 16 mg/kg. A dose of 12 mg/kg was selected for part 2. Part 2 assessed safety and prospective efficacy of DS-7300 in the selected tumor types, including mCRPC. DS-7300 was administered intravenously every 3 weeks in parts 1 and 2. Results: At data cutoff (August 8, 2021), 29 pts with mCRPC from the US and Japan were enrolled in parts 1 (n = 24) and 2 (n = 5). Pts enrolled in this study were heavily pretreated, with a median of 6.0 (range, 2-10) and 5.0 (range, 3-10) prior lines of therapy in parts 1 and 2, respectively. Baseline B7-H3 expression was highly prevalent in the study population. Enrolled pts were 44 to 82 years of age (median, 68.0 years) and had an ECOG performance status ≤1. Treatment-emergent adverse events (TEAEs) occurred in 29 pts (100.0%) in parts 1 and 2, with 7 pts (21.4%) with TEAEs leading to dose interruption, 2 pts (6.9%) with TEAEs leading to dose reduction, and no pts with TEAEs associated with drug discontinuation. The most common (≥20%) all-grade (Gr) TEAEs were nausea (65.5%), infusion-related reactions (IRRs; 34.5%), fatigue (34.5%), chills (31.0%), vomiting (31.0%), anemia (27.6%), diarrhea (27.6%), and dehydration (20.7%). Gr ≥3 TEAEs occurred in 10 pts (34.5%); the most common was anemia (17.2%). There were no Gr ≥3 treatment-related serious TEAEs (SAEs) reported. All IRR cases were Gr 1/2 and manageable with supportive care. No ILD/pneumonitis cases were reported. RECIST responses were observed in pts treated with DS-7300 between 6.4- and 16.0-mg/kg doses, including 6 partial responses (4 confirmed) and 15 stable diseases. The median duration of treatment was 13.9 weeks (range, 3-40 weeks) in part 1 and 6.0 weeks (range, 3-9.14 weeks) in part 2. At data cutoff, 8 pts (66.7%) in the 12.0-mg/kg group in part 1 and 4 pts (80.0%) in part 2 were ongoing treatment. Moreover, preliminary data indicate improvements in prostate-specific antigen (PSA) and bone metastases. Conclusions: DS-7300 was well tolerated with an acceptable safety profile in pts with mCRPC. The preliminary safety and efficacy data are encouraging and warrant further investigation. Clinical trial information: NCT04145622.