Treatment of Advanced Gastrointestinal Cancer with Genetically Modified Autologous Mesenchymal Stem Cells: Final Results of the Phase 1/2 TREAT-ME-1 Trial.

e14648 Background: TREAT-ME-1, a Phase 1/2 open-label, first-in-human, first-in-class trial, evaluated the safety, tolerability and efficacy of treatment with genetically modified autologous mesenchymal stromal cells (MSC),MSC_ apceth_101, in combination with ganciclovir in patients with advanced gastrointestinal adenocarcinoma. Methods: All patients (6 in Phase 1; 7 in Phase 2) received three treatment cycles of MSC_apceth_101 on Day 0, 7, and 14 followed by ganciclovir administration according to the manufacturer’s instructions for 48─72 hours after MSC_apceth_101 injection. Three patients were treated with a total dose of 1.5 x 106cells/kg MSC_apceth_101 (DL1). Ten patients were treated with a total dose of 3.0 x 106cells/kg MSC_apceth_101 (DL2). Immunological and inflammatory markers were assessed.Time to progression, overall survival was evaluated by RECISTwithin 56 days after administration of MSC_apceth_101 administration. Results: A total of 54 AEs occurred in 9/13 patients, thereof 18 AEs in three patients of DL1 and 36 AEs in six patients of DL2. Six AEs were CTC-AE grade 3, all other AEs were lower CTC-AE grades.Five SAEs emerged in two patients of DL1 and six SAEs in four patients of DL2. Eight patients achieved stable disease (change in target lesions of -2 to +28%). For all patients, the median time to progression was 1.9 months (95% CI: 1.3, 3.6 months). Median overall survival could not be estimated as 8/10 patients were still alive at the end of the study (one year) and therefore censored. Post-study observation of patients showed a median overall survival of 15.6 months (ranging from 2.2─27.0 months). Treatment with MSC_apceth_101 and ganciclovir did not induce a consistent increase or decrease in levels of any of the tumor markers analyzed. No clear trends in the immunological markers assessed were observed. Conclusions: MSC_apceth_101 in combination with ganciclovir was safe and tolerable in patients with advanced gastrointestinal adenocarcinoma, with preliminary signs of efficacy in terms of clinical stabilization of disease. Clinical trial information: NCT02008539.