Phase I, two-part, multicenter, first-in-human (FIH) study of DS-6000a in subjects with advanced renal cell carcinoma (RCC) and ovarian tumors (OVC).

• DOI: 10.1200/jco.2022.40.16_suppl.3002
• Publication Date: 2022-06-06T16:07:54Z
• Authors: Erika P. Hamilton; Shekeab Jauhari; Kathleen N. Moore; Brian I. Rini; Robert McLeod; Jie Lin; Nanae Izumi; Madan Gopal Kundu; Yusuke Myobatake; Abderrahmane Laadem; Yutaka Noguchi; Julius Kirui; David R. Spigel
• Keywords: Tolerability; Interim analysis

3002 Background: Cadherin 6 (CDH6) is part of the cadherin family, which involved with cell-cell adhesion, organ development, and epithelial-mesenchymal transition. CDH6 found to be overexpressed in various cancers, particularly RCC OVC. DS-6000a an antibody-drug conjugate, comprised humanized anti-CDH6 IgG1 monoclonal antibody attached a topoisomerase I (TOP1) inhibitor payload via cleavable linker. specifically binds on surface tumor cells internalized upon binding. The then released, resulting target cell apoptosis. In preclinical studies, inhibited growth induced regression CDH6-expressing Here, we report initial results from phase trial patients (pts) advanced OVC (NCT04707248). Methods: This dose-escalation (Part A) expansion B) study will recruit pts administered IV as monotherapy Day 1 21-day cycles. Part A assesses safety, tolerability, maximum tolerated dose or recommended for (RDE) using Bayesian optimal interval design; additional are enrolled examine safety efficacy. starting 1.6 mg/kg followed by 3.2, 4.8, 6.4, 8, 9.6 mg/kg. B assess tolerability efficacy at RDE. Results: interim presented. At data cutoff (19 NOV 2021), 22 had (7 RCC, 15 OVC). All received immune checkpoint majority platinum resistant (Pt-R) disease; median age was 63.5 years (range, 41-78); 4 1-12) prior lines therapy were administered; treatment duration 8.0 wks 3-33.14). Fifteen (68.2%) ongoing date. Treatment-emergent adverse events (TEAEs) occurred 19 (86.4%). Related TEAEs 17 (77.3%). most common related (>20%) fatigue nausea (45.5% each), vomiting (27.3%). Grade ≥3 (18.2%); neutropenia (13.6%). One patient (4.5%) 3 febrile neutropenia. dose-limiting toxicity thrombocytopenia (9.6 mg/kg) occurred. There no drug discontinuation due TEAE. Among evaluable pts, 2 partial responses (PRs; confirmed unconfirmed PR Pt-R OVC) observed; 9 stable disease. Moreover, 5 out 11 showed CA-125 GCIG criteria all responders Conclusions: this FIH acceptable early signals heavily pretreated OVC, support further clinical evaluation planned dose-expansion cohorts Clinical information: NCT04707248.