RT Journal Article
SR Electronic
T1 Nivolumab and sunitinib combination in advanced soft tissue sarcomas: a multicenter, single-arm, phase Ib/II trial
JF Journal for ImmunoTherapy of Cancer
JO J Immunother Cancer
FD BMJ Publishing Group Ltd
SP e001561
DO 10.1136/jitc-2020-001561
VO 8
IS 2
A1 Javier Martin-Broto
A1 Nadia Hindi
A1 Giovanni Grignani
A1 Javier Martinez-Trufero
A1 Andres Redondo
A1 Claudia Valverde
A1 Silvia Stacchiotti
A1 Antonio Lopez-Pousa
A1 Lorenzo D'Ambrosio
A1 Antonio Gutierrez
A1 Herminia Perez-Vega
A1 Victor Encinas-Tobajas
A1 Enrique de Alava
A1 Paola Collini
A1 Maria Peña-Chilet
A1 Joaquin Dopazo
A1 Irene Carrasco-Garcia
A1 Maria Lopez-Alvarez
A1 David S Moura
A1 Jose A Lopez-Martin
YR 2020
UL http://jitc.bmj.com/content/8/2/e001561.abstract
AB Background Sarcomas exhibit low expression of factors related to immune response, which could explain the modest activity of PD-1 inhibitors. A potential strategy to convert a cold into an inflamed microenvironment lies on a combination therapy. As tumor angiogenesis promotes immunosuppression, we designed a phase Ib/II trial to test the double inhibition of angiogenesis (sunitinib) and PD-1/PD-L1 axis (nivolumab).Methods This single-arm, phase Ib/II trial enrolled adult patients with selected subtypes of sarcoma. Phase Ib established two dose levels: level 0 with sunitinib 37.5 mg daily from day 1, plus nivolumab 3 mg/kg intravenously on day 15, and then every 2 weeks; and level −1 with sunitinib 37.5 mg on the first 14 days (induction) and then 25 mg per day plus nivolumab on the same schedule. The primary endpoint was to determine the recommended dose for phase II (phase I) and the 6-month progression-free survival rate, according to Response Evaluation Criteria in Solid Tumors 1.1 (phase II).Results From May 2017 to April 2019, 68 patients were enrolled: 16 in phase Ib and 52 in phase II. The recommended dose of sunitinib for phase II was 37.5 mg as induction and then 25 mg in combination with nivolumab. After a median follow-up of 17 months (4–26), the 6-month progression-free survival rate was 48% (95% CI 41% to 55%). The most common grade 3–4 adverse events included transaminitis (17.3%) and neutropenia (11.5%).Conclusions Sunitinib plus nivolumab is an active scheme with manageable toxicity in the treatment of selected patients with advanced soft tissue sarcoma, with almost half of patients free of progression at 6 months. Trial registration number NCT03277924.