Sintilimab plus Anlotinib in Patients with Pretreated Locally Advanced or Metastatic Sarcoma: A Prospective, Single-Arm, Phase II Clinical Trial

Advanced sarcomas have limited treatment options after standard therapy, and therefore we investigated the efficacy and safety of sintilimab plus anlotinib in this setting. Patients age 18 to 75 years with advanced sarcomas and prior systemic therapy were enrolled. Patients with untreated, primary chemotherapy-resistant tumor types, such as alveolar soft-part sarcoma and clear-cell sarcoma, were also included. Patients received sintilimab 200 mg (day 1) and anlotinib (8, 10, or 12 mg investigator-chosen, day 1-14) every 3 weeks. The primary endpoint was objective response rate (ORR). Secondary endpoints included progression-free survival (PFS), overall survival (OS), disease control rate (DCR), and adverse events (AE). The predictive value of tertiary lymphoid structure (TLS) was explored. A total of 42 patients were enrolled, and 40 (95.2%) patients were non-alveolar soft-part sarcoma. The ORR and DCR were 30.9% [95% confidence interval (CI), 16.4%-45.5%] and 76.2% (95% CI, 62.8%-89.6%), respectively, with a median follow-up duration of 15.4 months, and the median PFS was 5.0 months (95% CI, 2.8-10.2). The median OS was not reached. The most common AEs included elevated lactate dehydrogenase (28.57%), hypoproteinemia (21.43%), and increased thyroid-stimulating hormone (21.43%). The most common ≥ grade 3 AEs were hypertension (4.76%) and hyponatremia (4.76%). Two serious AEs (one hepatitis and one intestinal perforation) were recorded. The ORR in TLS-positive patients (n = 7) was significantly higher than that in TLS-negative patients (n = 28; 71.4% vs. 25.0%, P = 0.033). Therefore, sintilimab plus anlotinib demonstrated promising antitumor activity with manageable toxicity in advanced sarcomas, particularly among TLS-positive patients.