03275nas a2200493 4500008004100000022001400041245012000055210006900175260001200244490000600256520175600262653001002018653000902028653004102037653001102078653001102089653000902100653001602109653001402125653001202139653001402151653001602165100002502181700001702206700002302223700002902246700002002275700002202295700002402317700002502341700002402366700002302390700002502413700002802438700002202466700001902488700002402507700002002531700002702551700002502578700002002603700002602623856013202649 2020 eng d a2051-142600aNivolumab and sunitinib combination in advanced soft tissue sarcomas: a multicenter, single-arm, phase Ib/II trial.0 aNivolumab and sunitinib combination in advanced soft tissue sarc c2020 110 v83 a
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. NCT03277924.
10aAdult10aAged10aAntineoplastic Agents, Immunological10aFemale10aHumans10aMale10aMiddle Aged10aNivolumab10aSarcoma10aSunitinib10aYoung Adult1 aMartin-Broto, Javier1 aHindi, Nadia1 aGrignani, Giovanni1 aMartinez-Trufero, Javier1 aRedondo, Andres1 aValverde, Claudia1 aStacchiotti, Silvia1 aLopez-Pousa, Antonio1 aD'Ambrosio, Lorenzo1 aGutierrez, Antonio1 aPerez-Vega, Herminia1 aEncinas-Tobajas, Victor1 ade Alava, Enrique1 aCollini, Paola1 aPeña-Chilet, Maria1 aDopazo, Joaquin1 aCarrasco-Garcia, Irene1 aLopez-Alvarez, Maria1 aMoura, David, S1 aLopez-Martin, Jose, A uhttps://www.clinbioinfosspa.es/content/nivolumab-and-sunitinib-combination-advanced-soft-tissue-sarcomas-multicenter-single-arm