Abstract 1667TiP
Background
The development of tyrosine kinase inhibitors has revolutionized the treatment of advanced Gastrointestinal Stromal Tumor (GIST), but new strategies are needed to overcome resistance mechanisms that promote disease progression. Recently published studies on immune profiling in GIST demonstrated the presence of tumor-infiltrating immune cells and gene expression patterns associated with immune checkpoint inhibitors response. Moreover, preclinical studies have shown that VEGF inhibitors have immunomodulatory effects. Based on these data, we hypothesized that combining VEGF and PD-L1 inhibitors may have a synergistic effect and enhance the efficacy of both treatments. Given the favorable safety profile of axitinib and avelumab that has been demonstrated in phase II/III studies in renal cell carcinoma, this combination was chosen for evaluation in GIST patients after failure of standard therapy.
Trial design
AXAGIST is an open label, single arm, phase II trial with a Simon's two-stage design evaluating efficacy and safety of axitinib and avelumab in patients with unresectable/metastatic GIST. Key eligibility criteria are as follows: known mutational status KIT or PDGFRA, documented disease progression within 3 months before study entry, no more than 3 previous lines of treatment, which must include imatinib and sunitinib, performance status ≤ 2 and adequate organ function. Treatment includes avelumab (10mg/kg) IV q2wk and axitinib 5 mg orally BID. The primary end point is the progression-free survival rate at 3 months. Secondary endpoints include progression-free survival, overall survival, overall response rate, disease control rate and incidence of adverse events. If ≥ 5 of the first 17 pts are progression free at 3 months, patient entry will continue into the second stage until a total of 58 pts have been recruited. Correlation between tissue and blood-based biomarkers and clinical outcomes will be explored. This research and drug supply is financially supported by Pfizer, and is part of an alliance between Merck KGaA, Darmstadt, Germany and Pfizer Inc. The study protocol was initially developed during 19th MCCR Workshop.
Clinical trial identification
NCT04258956.
Editorial acknowledgement
Legal entity responsible for the study
Maria Sklodowska-Curie National Research Institute of Oncology.
Funding
This research and drug supply is financially supported by Pfizer, and is part of an alliance between Merck KGaA, Darmstadt, Germany and Pfizer Inc.
Disclosure
K. Kozak: Speaker Bureau/Expert testimony: BMS; Speaker Bureau/Expert testimony: Pfizer; Speaker Bureau/Expert testimony: Novartis; Speaker Bureau/Expert testimony: MSD. M.A. Pantaleo: Speaker Bureau/Expert testimony: Pfizer. P.G. Casali: Advisory/Consultancy: Deciphera Pharmaceuticals ; Advisory/Consultancy, Speaker Bureau/Expert testimony: Eisai ; Advisory/Consultancy, Speaker Bureau/Expert testimony: Eli Lilly; Advisory/Consultancy: Nektar Therapeutics; Speaker Bureau/Expert testimony: Pfizer; Speaker Bureau/Expert testimony: PharmaMar. P. Rutkowski: Advisory/Consultancy, Speaker Bureau/Expert testimony: BMS; Advisory/Consultancy, Speaker Bureau/Expert testimony: MSD; Advisory/Consultancy, Speaker Bureau/Expert testimony: Novartis; Advisory/Consultancy, Speaker Bureau/Expert testimony: Roche; Advisory/Consultancy, Speaker Bureau/Expert testimony: Pierre Fabre; Advisory/Consultancy, Speaker Bureau/Expert testimony: Pfizer. All other authors have declared no conflicts of interest.