Nivolumab and sunitinib in patients with advanced bone sarcomas: A multicenter, single-arm, phase 2 trial

Background: Herein, we present the results of the phase 2 IMMUNOSARC study (NCT03277924), investigating sunitinib and nivolumab in adult patients with advanced bone sarcomas (BS). Methods: Progressing patients with a diagnosis of BS were eligible. Treatment was comprised of sunitinib (37.5 mg/day on days 1-14, 25 mg/day afterword) plus nivolumab (3 mg/kg every 2 weeks). Primary end point was progression-free survival rate (PFSR) at 6 months based on central radiology review. Secondary end points were overall survival (OS), overall response rate (ORR) by Response Evaluation Criteria in Solid Tumors (RECIST) v1.1, and safety. Results: A total of 46 patients were screened, 40 patients entered the study, and 38 underwent central radiological review and were evaluable for primary end point. Median age was 47 years (range, 21-74). Histologies include 17 (43%) osteosarcoma, 14 chondrosarcoma (35%, 10 conventional, four dedifferentiated [DDCS]), eight (20%) Ewing sarcoma, and one (2%) undifferentiated pleomorphic sarcoma. The PFSR at 6 months was 42% (95% confidence interval [CI], 27-58). With a median follow-up of 39.8 months (95% CI, 37.9-41.7), the median PFS and OS were 3.8 months (95% CI, 2.7-4.8) and 11.9 months (95% CI, 5.6-18.2). ORR by RECIST was 5%, with two of 38 partial responses (one of four DDCS and one of 17 osteosarcoma), 19 of 38 (50%) stable disease, and 17 of 38 (45%) progressions. Grade >= 3 adverse events were neutropenia (six of 40, 15%), anemia (5/40, hypertension (6/40, 15%), 12.5%), ALT/AST elevation (5/40, 12.5%), and pneumonitis (1/40, 2.5%). Seventeen percent of patients discontinued treatment due to toxicity, including a treatment-related grade 5 pneumonitis Conclusion: The trial met its primary end point in the BS cohort with >15% of patients progression-free at 6 months. However, the toxicity profile of this regimen was relevant.