Abstract CT247: A Phase 1/2a, multicenter, open-label, non-randomized first-in-human study to assess the safety, tolerability, pharmacokinetics, and preliminary antitumor activity of DB-1303 in patients with advanced/metastatic solid tumors

Background: Epidermal growth factor receptor 2 (EGFR2 or HER2) has shown gene amplification/over-expression in more than 30% of all human cancers, including breast cancer, gastric, colon, salivary gland, bladder, and uterine serous carcinoma, and its overexpression in tumors is associated with poor prognosis. DB-1303 (developed by DUALITYBIO INC.) is an antibody-drug conjugate (ADC) comprised of a humanized anti-HER2 IgG1 monoclonal antibody (BAT0606), covalently linked to a proprietary DNA topoisomerase I inhibitor (P1003) via a cleavable linker containing maleimide tetrapeptide (GGFG), with a drug-to-antibody ratio (DAR) of approximately 8. Preclinical studies demonstrated a favorable safety profile and a potent antitumor activity of DB-1303 compared with approved HER2-ADC. These studies warrant further clinical development of the study drug. Methods: This is a global first-in-human Phase 1/2a study (NCT05150691) to assess the safety, tolerability, and anti-tumor activities of the study drug DB-1303 in patients with pretreated advanced/metastatic solid tumors. Patients should have histologically confirmed HER2-positive or HER2-expressing cancers who failed previously systemic therapies, ECOG 0-1, and adequate organ function. The dose escalation part will evaluate seven ascending dose levels of DB-1303 (accelerated titration design for the first dose level and “3+3” design for the rest dose levels) to determine recommended phase 2 dose (RP2D) or maximum tolerated dose (MTD). The study drug will be administrated iv infusion Q3W, and dose-limiting toxicity (DLT) will be assessed during Cycle 1 (1st 3 weeks). Phase 2a part will initiate after MTD and/or RP2D are determined. Phase 2a part only enrolls the patients with HER2-positive gastric, esophageal, or gastroesophageal junction adenocarcinoma, colorectal cancers, HER2 overexpression and HER2-low endometrial carcinoma, hormone receptor-positive (HR+)/HER2-low breast cancer, HER2-positive breast cancer, and activating HER2-mutated NSCLC. The study treatment of DB-1303 will continue until disease progression, withdrawal of consent, or unacceptable toxicity. Tumor responses will be assessed every 6-9 weeks with RECIST v1.1. The study planned to enroll 253 patients from sites in the United States, Australia, and China (88 patients in Phase I and 165 patients in Phase 2a). Citation Format: Erika Hamilton, Jian Zhang, Liming Liu, Jie Gao, Rong Shi, Shengxue Liu, Gu Wei, Yang Qiu, Kathleen Moore. A Phase 1/2a, multicenter, open-label, non-randomized first-in-human study to assess the safety, tolerability, pharmacokinetics, and preliminary antitumor activity of DB-1303 in patients with advanced/metastatic solid tumors [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 2 (Clinical Trials and Late-Breaking Research); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(8_Suppl):Abstract nr CT247.