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

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.