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 Martin-Broto, Javier
A1 Hindi, Nadia
A1 Grignani, Giovanni
A1 Martinez-Trufero, Javier
A1 Redondo, Andres
A1 Valverde, Claudia
A1 Stacchiotti, Silvia
A1 Lopez-Pousa, Antonio
A1 D'Ambrosio, Lorenzo
A1 Gutierrez, Antonio
A1 Perez-Vega, Herminia
A1 Encinas-Tobajas, Victor
A1 de Alava, Enrique
A1 Collini, Paola
A1 Peña-Chilet, Maria
A1 Dopazo, Joaquin
A1 Carrasco-Garcia, Irene
A1 Lopez-Alvarez, Maria
A1 Moura, David S
A1 Lopez-Martin, Jose A
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.