Phase II trial of sintilimab in cancer of unknown primary.

825 Background: CUP is an aggressive rare malignancy accounting for 2-4% of all cancers. Beyond frontline therapy, predominantly systemic cytotoxic chemotherapy, no clear standard of care exists. Preliminary data suggests that immune-checkpoint inhibitors have encouraging activity in patients with CUP. Prior anti-PD1 agents have demonstrated response rates of 21-23%. We studied the role of sintilimab, an anti-PD1 antibody, in CUP. Methods: In this phase II study (NCT05024968)10 patients (of planned 40) were enrolled prior to closure of the study due to sponsor funding. Patients were eligible if they were refractory or intolerant to one line of systemic therapy or had a contraindication for cytotoxic chemotherapy. Patients received sintilimab 200 mg IV every 3 weeks. Paired tumor biopsies were collected for biomarker analysis. The primary endpoint was confirmed objective response rate (cORR) by RECISTv1.1 assessed by independent radiology review. Key secondary endpoints were safety, disease control rate (DCR), duration of response (DOR), progression-free survival (PFS), overall survival (OS), and Quality of Life (QOL). Median PFS and OS were calculated according to the Kaplan-Meier method. Adverse events (AEs) were assessed according to CTCAE v5.0. Results: Between 10/2021 and 2/2023, 10 patients were enrolled and treated. Median age was 65 years and 30% of patients were female. Seven (70%) had poorly differentiated carcinoma. Patients received a median of 1 line of therapy prior to enrollment. Median follow-up was 19.8 months. All patients were evaluable for toxicity and response. The cORR was 40% (95% CI, 12.2 to 73.8); one (10%) patient with a complete response and 3 (30%) with partial responses. The median DOR was 15.7 months. Three patients (30%) had Grade ≥ 3 (no grade 4/5) treatment-related AEs including 2 patients with sepsis and 1 patient with leukocytosis. Median PFS and OS were 4.4 months (95% CI, 2.0 to 25.4) and 25.4 months (95% CI, 4.0 to 27.4), respectively. Conclusions: Anti-PD1 therapy with Sintilimab demonstrated significant anti-tumor activity for select patients with refractory CUP with safety profile consistent with other anti-PD1 agents. Ongoing correlative studies may inform the role of biomarker selection for immunotherapy in CUP. Clinical trial information: NCT05024968 .