27 - Freie Mitteilung
15. Mai 2019, 15:30 - 17:00, Bellavista 2, 6. OG
ITPP - a novel hypoxia-modifier as a potential antitumor agent in patients with hepato-pancreato-biliary neoplasms – Results of a phase IB clinical trial
P. Limani1, M. A. Schneider1, M. Linecker1, B. Pestalozzi1, P. Kron1, A. Jetter1, C. Nicolau2, J.-M. Lehn3, H. Petrowsky1, B. Humar1, R. Graf1, P.-A. Clavien1, Presenter: P. Limani1 (1Zurich, 2Boston/USA, 3Strasbourg/FR)
Hypoxia occurs in solid tumors and leads to increased invasiveness due to epithelial-mesenchymal transformation, activation of the Warburg effect and decreased anti-tumor immunological responses. The novel anti-hypoxic molecule myo-inositoltrispyrophosphate (ITPP, OXY111A) acts as an allosteric effector of hemoglobin and counteracts counteracts hypoxia-induced tumor aggressiveness showing decreased tumor burden and increased survival in five different animal solid tumor models both applied as monotherapy and increased beneficial effects when followed by standard chemotherapy.
The present study is a first in-human exploratory, prospective, open-labelled, mono-centric Phase IB study according to a classical 3+3 dose escalation design (ClinicalTrials.gov Identifier: NCT02528526) in patients with non-resectable primary and secondary tumors of the liver, pancreas, and biliary tract. The study intervention consists of 9 infusions of ITPP over 3 weeks, followed by administration of conventional cytotoxic chemotherapy. Primary endpoint is the determination of safety and tolerability of ITPP, secondary endpoint is assessment of efficacy/tumor response with FDG-PET/CT and MRI.
30 patients were included between 04/2015 and 12/2017, with 1 patient withdrawn from the study and 22 assessed for the primary endpoint. ITPP administration was safe, well tolerated and no dose-limiting toxicity was encountered up to the maximal dose currently tested (Cohort 7: 12’390mg/m2). 6 serious adverse events were recorded, none of it related to ITPP. 30 adverse events occurred, with 15 of those judged to be possibly or definitively related to ITPP, with 11 patients experiencing hypercalcemia, 2 hyponatremia, 1 hypomagnesemia and 1 hypokalemia (all CTCAE Grade 1). 8 patients had radiological disease stabilization under ITPP treatment with 3 patients experiencing a decrease in tumor markers. 4 patients had stable disease under consequent chemotherapy, while 5 benefited of a strong partial response.
Administration of ITPP before chemotherapy is safe and well tolerated with neglible side-effects. Further exploration of its anti-tumor efficacy in Phase II/III trials is highly warranted.