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.
Manish R. Patel, Melissa L. Johnson, Gerald S. Falchook, Toshihiko Doi, Claire F. Friedman, Sarina A. Piha‐Paul, Martin Gutierrez, Toshio Shimizu, Ben Cheng, Meng Qian, Xiaozhong Qian, Yusuke Myobatake, Abderrahmane Laadem, Naoto Yoshizuka, Tracey Hammett, Julius Kirui, Hendrik‐Tobias Arkenau
Abstract
87 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.