Phase IB/II trial of durvalumab plus doxorubicin combination in patients with advanced soft-tissue sarcoma.

11552 Background: We conducted an open-label, phase IB/II study to determine the activity and safety of the standard-of-care, doxorubicin in combined with the anti-PD-L1 immune checkpoint inhibitor, durvalumab, in patients with anthracycline-naïve soft tissue sarcoma (STS) and identified patients who would likely benefit from combination treatment. Methods: In this trial (NCT03798106), we enrolled patients with metastatic and/or recurrent STS had not received anthracycline chemotherapy and PD-L1/PD-1 inhibitor. Phase IB assessed the safety and tolerability of doxorubicin level 1 (75mg/m 2 ) and level -1 (60 mg/m 2 ) in combination with durvalumab 1500 mg once every 3 weeks until documented disease progression or unacceptable toxicity. Phase II assessed the efficacy, with the primary endpoint to detect a difference in objective response between 5% and 20%. Results: No DLTs were observed during the phase IB (n=3), therefore recommended phase II dose was defined at doses of 75/m 2 doxorubicin and proceed the phase II part. Of 41 evaluable patients, 1 (2.4%) achieved complete response, 12 (29.3%) achieved confirmed partial response, yielding an objective response rate of 31.7%. The median progression free survival was 8.2 months (95% CI, 7.3-9.0) and median overall survival was 24.1 months (95% CI, 7.6-40.3). Treatment-related adverse events of grade 3 or 4 occurred in neutropenia (n = 23, 53.4%), thrombocytopenia (n=6, 13.9%), and anemia (n=5, 11.6%). The prespecified genomic analysis with targeted and transcriptomic sequencing will be available at the meeting. Conclusions: Durvalumab combined with doxorubicin demonstrated promising efficacy in an unselected STS cohort, with a manageable toxicity profile. Clinical trial information: NCT03798106 .