Activity results of the GATTO study, a phase Ib study combining the anti-TA-MUC1 antibody gatipotuzumab with the anti-EGFR tomuzotuximab or panitumumab in patients with refractory solid tumors.
Authors: Garralda Elena , Del Conte Gianluca , Macchini Marina , Matos Ignacio , Klinghammer Konrad Friedrich , Saavedra Santa Gadea Omar , Fiedler Walter M. , Rolling Christina C , Kebenko Maxim , Raspagliesi Francesco , Larusso Domenica , ahrens-Fath Isabelle , Habel Beate , Baumeister Hans , Zurlo Alfredo , Ochsenreither Sebastian 
Published: June 2021

2522

Background: The phase I GATTO study explored the feasibility, tolerability and preliminary activity of combining Gatipotuzumab (GAT), a novel humanized monoclonal antibody binding to the tumor-associated epitope of mucin-1 (TA-MUC1), and an anti-EGFR antibody. Preclinical evidence suggests a complex interaction between TA-MUC1 and EGFR on the cell surface of epithelial tumors and synergistic antibody dependent cell cytotoxicity activity with the double targeting. Methods: Initially 20 patients with refractory metastatic disease were treated with GAT administered at 1400 mg Q2W in combination with the glyco-optimized anti-EGFR antibody Tomuzotuximab (TOM) at 1200 mg Q2W. Due to the risk of infusion related reactions, three cycles of TOM were given before start of combined treatment with GAT. After this regimen was proven safe and no DLT was observed, 30 additional patients including colorectal cancer (CRC) already treated with anti-EGFR antibodies, non-small cell lung cancer (NSCLC), head and neck and breast cancers received TOM and GAT administered at the same doses, with GAT treatment starting already one week after the first dose of the anti-EGFR antibody. As allowed in the study expansion, Panitumumab (PAN) was used in place of TOM in 9 CRC patients at investigator’s choice. Results: By the time of the final analysis in January 2021, 52 patients were enrolled, and 50 received at least one dose of both GAT and anti-EGFR antibodies. Safety was overall good and results are reported in a separate abstract. Because of the difference in treatment schedule, activity results of the two parts of the study are summarized separately. There were 2 and 4 RECIST partial responses in the first and second part of the study, all in CRC patients. In the expansion phase, the median Progression Free Survival (PFS) of CRC patients who received TOM (10) and PAN (9) was 1.9 and 5.5 months, respectively. There were 2 responses in each subgroup and the duration of response was 3.8 and 7.2 months in patients receiving TOM and PAN, respectively. The PFS for NSCLC was 5.3 months and 2 heavily pretreated patients achieved a prolonged control of disease of 10.6 and 9.4 months. The trial was accompanied by a comprehensive translational research program for identification of biomarkers, including soluble TA-MUC1 in serum. In the extension phase patients with baseline values above median appeared to have improved PFS and overall survival; this was not the case for patients of the first part of the study who received GAT only after 3 doses of TOM. Conclusions: Combination of TA-MUC1 and EGFR targeting antibody is safe and feasible. Interesting anti-tumor activity was observed in heavily pretreated CRC and NSCLC patients. Levels of soluble TA-MUC1 may have predictive value and potentially be a companion biomarker for further development of the combination Clinical trial information: NCT03360734.