Sintilimab plus anlotinib in patients with advanced sarcomas (SINANLOSARC): A single-centre, single-arm, phase II trial

BackgroundStudies showed that intratumoral tertiary lymphoid structures (TLSs) are associated with improved outcome in patients with soft tissue sarcomas. We conducted a phase II trial to investigate the efficacy and safety of sintilimab plus anlotinib for advanced sarcomas and to explore the predictive role of TLSs in this clinical setting.MethodsThis trial was conducted in Shandong Cancer Hospital and Institute. Patients were eligible if they were aged 18 to 75 years, and had histologically confirmed, measurable advanced bone or soft tissue sarcomas; an ECOG performance status of 0-1; and progressive disease after previous treatment (except for patients with alveolar soft part sarcoma or clear cell sarcoma). The patients received 200 mg sintilimab once on day 1 and anlotinib (investigator’s choice of 8 mg; or 10 mg; or 12mg) once daily on days 1-14 every 3 weeks. The primary endpoint was the objective response rate (ORR). The secondary endpoints included progression-free survival (PFS), overall survival (OS), disease control rate (DCR), adverse events (AEs), and the predictive value of TLSs.ResultsFrom December 2021 to February 2024, 42 patients (median [range] age, 54.5 [18-72] years) were enrolled, only 2 (4.76%) of whom had alveolar soft part sarcomas. The ORR and DCR were 30.95% (95%CI, 19.07-46.03%) and 76.19% (95%CI, 61.47-86.52%), respectively. With a median follow-up duration of 13.97 months (range, 0.9–29.5), the median PFS was 5.1 months (95% CI, 1.3-8.8). The median OS was not reached. The most common AEs included elevated lactate dehydrogenase (28.57%), hypoproteinemia (21.43%), electrocardiogram T-wave abnormality (16.67%), and hyperuricemia (16.67%). The most frequent ≥ grade 3 AEs were hypertension (4.76%) and hyponatremia (4.76%). 2 serious AEs (1 hepatitis and 1 intestinal perforation) were recorded. No treatment-related death occurred. Patients with TLSs had a significantly higher ORR and longer PFS.ConclusionsSintilimab plus anlotinib has encouraging efficacy and manageable toxicity in patients with advanced sarcomas. TLS is a potential predictive biomarker to improve patients' selection for sintilimab plus anlotinib treatment.Clinical trial identificationChiCTR2100055071.FundingHas not received any funding.DisclosureAll authors have declared no conflicts of interest.