Solid Tumor Phase 1 Clinical Trial: GO-203

Rationale

GO-203 is a stable, rationally designed D-amino acid peptide that targets the MUC1-C cytoplasmic domain at the CQC motif, which is necessary and sufficient for the formation of MUC1-C homodimers and thereby its oncogenic function. GO-203 is active against MUC1-expressing human cancer cells growing in vitro and as tumor xenografts in mice.

Preclinical toxicology studies

Safety assessment of GO-203 was performed in rat and dog, which share homology with the human MUC1-C cytoplasmic domain. The results of the PK and safety assessment evaluations demonstrated an excellent safety profile for GO-203 and supported the first-in-human Phase 1 clinical trial.

Phase 1 human clinical study

Study GO-2C-001 was a Phase 1, multi-center, open-label, dose-escalation study evaluating the safety, PD, and PK of GO-203 in patients with advanced solid tumors or lymphomas. The primary objectives were to define DLTs and establish the MTD. Twenty-three patients were enrolled with 21 patients receiving at least one dose of GO-203, and 15 patients completing the study. GO-203 doses of 1.6, 3.2, 6.5, 12.5, 19.0, 25.5, and 38.0 mg/m2 were administered intravenously each day for 21 days. A highly acceptable toxicity profile was seen with CTCAE Grade 1-3 AEs reported in 20/21 treated patients. Most of the AEs were of CTCAE Grade 1 or 2 severity, and the majority were unlikely related or not related to GO-203 treatment. An asymptomatic, reversible increase in liver enzymes was observed at the higher doses. The dose of 25.5 mg/m2/day was defined as the MTD. The PK of GO-203 was dose-proportional with a terminal half-life of 5 to 16 hours.