Phase II study of the antibody-drug conjugate TAK-264 (MLN0264) in patients with metastatic or recurrent adenocarcinoma of the stomach or gastroesophageal junction expressing guanylyl cyclase C.

Background The first-in-class antibody-drug conjugate TAK-264 (formerly MLN0264) consists of an antibody targeting guanylyl cyclase C (GCC) conjugated to monomethyl auristatin E (MMAE) via a peptide linker. This phase II study evaluated the efficacy and safety of TAK-264 in patients with adenocarcinoma of the stomach or gastroesophageal junction expressing GCC, who had progressed on ≥1 line of prior therapy. Methods This study used a two-stage design, with an interim analysis conducted after stage I to determine whether to continue to stage II or discontinue on the grounds of futility. Adult patients with gastric and gastroesophageal junction adenocarcinoma expressing low, intermediate, or high GCC levels received TAK-264 1.8 mg/kg as a 30-min intravenous infusion once every 21 days, for up to 1 year. The primary endpoint was objective response rate. Radiographic assessments of tumor burden were performed every 2 cycles (6 weeks). Results A total of 38 patients participated in the study. Patients received a median of 2 (range 1-14) cycles; 8 (21%) received at least 6 cycles. The most common adverse events were nausea (53%), fatigue (32%), and decreased appetite (29%). Grade ≥3 events including anemia, diarrhea, and neutropenia were seen in 14 (37%) patients. Systemic exposure to TAK-264 was maintained throughout each treatment cycle. Two patients (6%) with intermediate GCC expression had objective responses. Conclusions TAK-264 demonstrated a manageable safety profile in this patient population. The stage I interim analysis did not support continuation to stage II of the study.