SO-010Preliminary results in colorectal cancer (CRC) patients enrolled in the GATTO study, a phase I study of Tomuzotuximab in combination with Gatipotuzumab in patients with EGFR positive solid tumors

Introduction: TO (Tomuzotuximab) is a second-generation anti-EGFR antibody that specifically binds to EGFR. GAT (Gatipotuzumab) is a novel humanized monoclonal antibody, which recognizes the tumor-associated epitope of mucin-1 (TA-MUC1). Both antibodies are glyco-engineered to potentiate antibody-dependent cellular cytotoxicity (ADCC). Preclinical evidence suggests a complex interaction between EGFR and TA-MUC1 expressed on the cell surface and shows a synergistic antibody dependent cell cytotoxicity activity with dual targeting of these molecules. GATTO is an open label phase Ib study in refractory patients (pat) with EGFR positive metastatic solid tumors. aiming to assess the tolerability, safety and preliminary activity of the combined treatment with the two antibodies. Methods: TO and GAT were administered at 1200 mg and 1400 mg Q2W respectively. Pat receive 3 doses of TO before start of combination treatment with GAT. The first 6 pat have been enrolled into a safety run-in phase where the number of dose-limiting toxicities (DLTs) has been evaluated. Safety criteria were met (i.e. 0 DLT), and the initial dose was unchanged and used for all the recruited pat. Secondary endpoints include overall response rate, duration of response, progression-free and overall survival. Extensive pharmacokinetics (PK) and pharmacodynamics (PD) is in progress. As of January 15, 2019 the study enrolled 20 pat; we report here the results in the cohort of 6 CRC pat, 4 of which had no known K-RAS mutation (K-RAS WT) and had progressed after prior anti-EGFR antibody treatment Results: Treatment was well tolerated, with 2 pat (33%) experiencing infusion related reactions (IRR) of grade 1 CTCAE during the first infusion of TO. No IRR were observed at later infusions. Five of 6 pat developed rash (grade 1 in 3 and grade 3 in 2 pat), 1 pat fatigue and 2 pat hypomagnesemia. Response assessment revealed that while the 2 pat with known K-RAS mutation progressed rapidly, 3 of the 4 K-RAS WT pat had clinical benefit (1 confirmed PR, 1 unconfirmed PR and 1 prolonged SD according to RECIST) and median PFS in this small subgroup of pat was 6 months. PK and PD results will also be reported. Conclusion: Preliminary results of this study warrant further investigation of the combination of TO and GAT in refractory pat with K-RAS WT CRC.