Phase I, first-in-human study of AbGn-107, a novel antibody-drug conjugate (ADC), in patients with gastric, colorectal, pancreatic or biliary cancers.

e16771 Background: AbGn-107 is an ADC directed against AG-7 antigen, a Lewis A-like glycol-epitope expressed in 24-61% of gastric (G), colorectal (CRC), pancreatic (PDA), and biliary (BIL) cancers. Based on promising antitumor activity of AbGn-107 in both in vitro and in vivo preclinical studies, we performed a Phase Ia trial in patients with the aforementioned GI malignancies. Methods: Standard 3+3 dose escalation was used. Key eligibility included locally advanced or metastatic G, CRC, PDA, or BIL cancer, previously treated, ECOG PS 0-1; positive AG-7 expression was not required. Two dosing intervals were tested: AbGn-107 administered i.v. Q4 weeks (at doses ranging from 0.1-1.2 mg/kg) and Q2 weeks (at doses from 0.8-1.0 mg/kg). Dose limiting toxicities (DLT) were based on grade 3/4 hematologic and non-heme AEs occurring during the initial 4-week rx window. Patients were treated until disease progression or unacceptable toxicity, with tumor assessments Q8 weeks. 1o objectives: safety and MTD; 2o objectives: PK, immunogenicity, and efficacy defined by ORR (RECIST 1.1). Results: 35 patients were enrolled across 6 dose levels (median age 61.5 yo (range 40 – 81); G (0)/CRC (12)/PDA (20)/BIL (3); median # lines of prior rx = 3 (range 1-7). Safety: 5 patients experienced Grade 3 or 4 neutropenia, all at higher dose levels, inc. 1 episode of febrile neutropenia. Other frequent drug-related AEs, mostly grade 1/2, inc. fatigue (29%), nausea (20%), and diarrhea (14%). DLTs included grade 4 CK elevation (n = 1) at 0.8 mg/kg Q4W and grade 3 arthralgias (n = 1) at 1.2 mg/kg Q4W. Based on safety profile and PK data, 1.0 mg/kg Q2W was selected as the dose schedule for cohort expansion phase. Efficacy: Median duration of treatment = 56 days (range, 8 – 225 days). Six pts have demonstrated a minor response by RECIST (range, -1.3 to -21.1%); 4 pts (all PDA) have had durable dz control > 180 days. Conclusions: Overall, AbGn-107 appears well-tolerated with encouraging prelim signs of efficacy in unselected pts with heavily pre-treated advanced GI cancers. Updated safety and efficacy data will be provided at the time of the meeting for the cohort expansion phase of this study (currently open across multiple sites in U.S. and Taiwan), in which subjects with G, CRC, PDA, and BIL cancers are pre-screened for high levels of AG-7 tumor expression. Clinical trial information: NCT02908451 .