Exploratory Study on Toripalimab and Anlotinib Combined With Standard Chemotherapy for Refractory Dermatofibrosarcoma Protuberans

Exploratory Study on Toripalimab and Anlotinib Combined With Standard Chemotherapy for Refractory Dermatofibrosarcoma Protuberans

This study aims to evaluate the efficacy and safety of toripalimab and anlotinib hydrochloride combined with standard chemotherapy in patients with refractory dermatofibrosarcoma protuberans (DFSP) resistant to imatinib therapy, and to provide evidence for the exploration of DFSP treatment.

Inclusion Criteria

1. Male or female patients aged ≥18 years.

2. Locally advanced, unresectable or metastatic dermatofibrosarcoma protuberans (DFSP) with histologically confirmed specific subtypes; disease progression following standard imatinib therapy, or no satisfactory alternative treatment options. Specific subtypes include: fibrosarcomatous DFSP (FS-DFSP) or DFSP with transformation to high-grade sarcoma, such as undifferentiated pleomorphic sarcoma, leiomyosarcoma, rhabdomyosarcoma, etc.

3. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.

4. At least one measurable lesion at baseline according to RECIST 1.1 criteria.

5. Adequate organ and bone marrow function within 14 days prior to enrollment:

   • Hemoglobin ≥9 g/dL
   • Platelet count ≥75,000/mm³
   • Absolute neutrophil count ≥1500/mm³
   • Serum albumin ≥2.5 g/dL
   • PT, aPTT, and INR ≤1.5 × ULN
   • AST and ALT ≤3 × ULN, or <5 × ULN in patients with liver metastases
   • Total bilirubin ≤1.5 × ULN (without liver metastasis), or <3 × ULN (with Gilbert syndrome or liver metastasis at baseline)
   • Creatinine clearance ≥30 mL/min calculated by the Cockcroft-Gault formula

6. Left ventricular ejection fraction (LVEF) ≥50% as assessed by ECHO or MUGA scan within 28 days prior to enrollment.

Exclusion Criteria

Patients with any of the following will be excluded:

1. Spinal cord compression, leptomeningeal disease, or clinically active central nervous system (CNS) metastases.

2. Active primary immunodeficiency, known HIV infection, active hepatitis B virus (HBV) or hepatitis C virus (HCV) infection.

3. History of non-infectious interstitial lung disease (ILD)/non-infectious pneumonitis requiring corticosteroid therapy, current ILD/non-infectious pneumonitis, or suspected ILD/non-infectious pneumonitis that cannot be ruled out by imaging at screening.

4. Myocardial infarction within 6 months prior to enrollment, symptomatic congestive heart failure (CHF, NYHA class II-IV), unstable angina, or recent cardiovascular event (including stroke) within <6 months.

5. Pulmonary criteria:

   1. Clinically significant pulmonary comorbidities including but not limited to underlying pulmonary disease (e.g., pulmonary embolism, severe asthma, severe COPD, restrictive lung disease, pleural effusion within 3 months before enrollment);
   2. Documented autoimmune, connective tissue, or inflammatory disease (e.g., rheumatoid arthritis, Sjögren's syndrome, sarcoidosis, etc.) or suspected pulmonary involvement at screening; full disease details must be documented in the eCRF;
   3. Prior pneumonectomy.

6. Poor compliance unable to cooperate with study treatment and procedures.