NCT04172805

Anlotinib Combined With Toripalimab in Refractory and Advanced Soft-tissue Sarcoma

A Single-arm, Open, Phase II Study of Anlotinib Combined With Toripalimab in Refractory and Advanced Soft-tissue Sarcoma

• Status: Unknown
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 70 (estimated)
• Sponsor: Sun Yat-sen University · Academic / Other
• Sex: All
• Age: 18 Years – 70 Years
• Healthy volunteers: Not accepted

Summary

Soft tissue sarcoma (STS) is a relatively rare type of malignant tumor with an incidence of 1-2/100000. For unresectable or widely disseminated advanced STS, a combined clinical trial is the best way to obtain evidence-based medical evidence. Anlotinib, a multi-target receptor tyrosine kinase inhibitor (TKI), is effective for various histological types of STS and the safety is tolerable. TKIs may reverse drug resistance or inefficiency of immunoassay inhibitors, and combination therapy has shown preliminary efficacy in a variety of tumors. Because of the poor prognosis of refractory and advanced STS, there is no standard second-line treatment. Therefore, combined therapies based on the original targeted drugs would be paid more concentrations in the future. We focus on exploring the feasibility of combination of anlotinib and Toripalimab monoclonal antibody in advanced, refractory and progressive soft tissue sarcoma after failure of standard treatment, and look forward to further improving the efficacy of soft tissue sarcoma.

Detailed description

Soft tissue sarcoma (STS) is a relatively rare type of malignant tumor. For patients with recurrent/distant metastasis/unresectable advanced soft tissue sarcoma, chemotherapy with doxorubicin and ifosfamide is the standard treatment, but the effect is limited. Targeted drugs represented by anti-angiogenesis targeted drugs have had certain clinical benefits in the treatment of sarcoma. Among them, anlotinib, a multi-target receptor tyrosine kinase inhibitor, is effective for STS of various tissue types and the safety is tolerable. Previous clinical studies have found that anlotinib has a certain effect on a variety of solid tumors including thyroid cancer, lung cancer, soft tissue sarcoma, and kidney cancer. In 2016, a phase II clinical study evaluated the efficacy and safety of anlotinib advanced STS, especially synovial sarcoma and alveolar soft tissue sarcoma. The study included 154 patients with evaluable efficacy, with an ORR of 10.13% and a median PFS of 5.63 months. Even so, the limited efficacy of targeted drugs remains a bottleneck. For advanced unresectable or widely disseminated soft tissue sarcomas, a combined clinical trial is the best way to obtain evidence-based medical evidence. In recent years, anti-PD-1 antibodies have been reported as effective treatment in solid tumors, and their clinical application has become increasingly widespread. The anti-PD-1 antibody Toripalimab has also been listed recently, and its clinical application prospects are huge. Anti-PD-1 antibodies also have been proved effect better in combination with targeted therapies. Multiple in vitro studies have shown that low-dose anti-angiogenesis targeted drugs can reduce hypoxia, increase CD8+ T cell infiltration, reduce tumor-associated macrophage (TAM) recruitment in non-small cell lung cancer and reduce tumor and serum. The level of TGF-β is increased, thereby enhancing the anti-PD-1 antibody effect and significantly inhibiting tumor growth and metastasis. At the same time, by evaluating the therapeutic effects of combination therapy in other tumors, we aim to investigate that anti-angiogenesis targeted drugs combined with anti-PD-1 antibodies have considerable potential for sarcoma treatment. At present, a number of clinical trials of anti-angiogenesis targeted drugs combined with anti-PD-1 antibody for tumor treatment are underway or will be carried out, but the clinical study of anti-PD-1 antibody with anlotinib has not yet started. In response to the above problems, the aim of this study was to explore the efficacy and to assess the safety of anti-PD-1 antibody in the treatment of refractory and advanced STS patients with first-line treatment failure, which would provide patients with STS better treatment options.

Conditions

• Sarcoma,Soft Tissue

Interventions

Type	Name	Description
DRUG	anlotinib and toripalimab	Anlotinib 12mg orally per day, two weeks on , one week off; 240 mg of toripalimab (fixed dose) every three weeks. Repeat every three weeks. Patients with disease control (CR + PR + SD) and tolerable adverse reactions continued to take medication until the researchers concluded that patients were not suitable to continue medication or the efficacy evaluation was disease progression (PD). No other antineoplastic treatment can be given during the treatment.

Timeline

• Start date: 2020-03-13
• Primary completion: 2024-03-01
• Completion: 2024-05-15
• First posted: 2019-11-21
• Last updated: 2023-04-12

Locations

1 site across 1 country: China