Nivolumab and sunitinib combination in advanced soft tissue sarcomas: a multicenter, single-arm, phase Ib/II trial

• DOI: 10.1136/jitc-2020-001561
• Publication Date: 2020-11-17T21:44:09Z
• Authors: Javier Martin-Broto; Nadia Hindi; Giovanni Grignani; Javier Martinez-T...; Andres Redondo; Claudia Valverde; Silvia Stacchiotti; Antonio Lopez-Pousa; Lorenzo D'Ambrosio; Antonio Gutierrez; Herminia Perez-Vega; Victor Encinas-To...; Enrique de Alava; Paola Collini; Maria Peña-Chilet; Joaquin Dopazo; Irene Carrasco-Ga...; Maria Lopez-Alvarez; David S Moura; Jose A Lopez-Martin
• Keywords: Clinical endpoint

Background Sarcomas exhibit low expression of factors related to immune response, which could explain the modest activity PD-1 inhibitors. A potential strategy convert a cold into an inflamed microenvironment lies on combination therapy. As tumor angiogenesis promotes immunosuppression, we designed phase Ib/II trial test double inhibition (sunitinib) and PD-1/PD-L1 axis (nivolumab). Methods This single-arm, enrolled adult patients with selected subtypes sarcoma. Phase Ib established two dose levels: level 0 sunitinib 37.5 mg daily from day 1, plus nivolumab 3 mg/kg intravenously 15, then every 2 weeks; −1 first 14 days (induction) 25 per same schedule. The primary endpoint was determine recommended for II (phase I) 6-month progression-free survival rate, according Response Evaluation Criteria in Solid Tumors 1.1 II). Results From May 2017 April 2019, 68 were enrolled: 16 52 II. as induction nivolumab. After median follow-up 17 months (4–26), rate 48% (95% CI 41% 55%). most common grade 3–4 adverse events included transaminitis (17.3%) neutropenia (11.5%). Conclusions Sunitinib is active scheme manageable toxicity treatment advanced soft tissue sarcoma, almost half free progression at 6 months. Trial registration number NCT03277924 .