Safety and activity of ibrutinib in combination with nivolumab in patients with relapsed non-Hodgkin lymphoma or chronic lymphocytic leukaemia: a phase 1/2a study

Publication date: Available online 11 January 2019Source: The Lancet HaematologyAuthor(s): Anas Younes, Joshua Brody, Cecilia Carpio, Armando Lopez-Guillermo, Dina Ben-Yehuda, Burhan Ferhanoglu, Arnon Nagler, Muhit Ozcan, Irit Avivi, Francesc Bosch, Maria Dolores Caballero Barrigón, Andrzej Hellmann, Bryone Kuss, David D F Ma, Fatih Demirkan, Münci Yağci, Netanel A Horowitz, Paula Marlton, Raul Cordoba, Tomasz WrobelSummaryBackgroundPreclinical studies have shown synergistic antitumour effects between ibrutinib and immune-checkpoint blockade. The aim of this study was to assess the safety and activity of ibrutinib in combination with nivolumab in patients with relapsed or refractory B-cell malignant diseases.MethodsWe did a two-part, open-label, phase 1/2a study at 21 hospitals in Australia, Israel, Poland, Spain, Turkey, and the USA. The primary objective of part A (dose escalation) was to assess the safety of daily oral ibrutinib (420 mg or 560 mg) in combination with intravenous nivolumab (3 mg/kg every 2 weeks) to ascertain a recommended phase 2 dose in patients with relapsed or refractory high-risk chronic lymphocytic leukaemia or small lymphocytic lymphoma (del17p or del11q), follicular lymphoma, or diffuse large B-cell lymphoma. Dose optimisation was investigated using a modified toxicity probability interval design. The primary objective of the part B expansion phase was to establish the preliminary activity (the proportion of patients who achieved an overall respo...
Source: The Lancet Haematology - Category: Hematology Source Type: research