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

Overview

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.

Interventions

• Drug Toripalimab
  All enrolled patients will receive study intervention starting on Day 1 of each 3-week cycle until disease progression, intolerable toxicity, or study withdrawal: Toripalimab 240 mg (fixed dose) administered intravenously once every 3 weeks (Q3W).
• Drug Anlotinib
  All enrolled patients will receive study intervention starting on Day 1 of each 3-week cycle until disease progression, intolerable toxicity, or study withdrawal: Anlotinib 10 mg administered orally once daily on Days 1-14 of each 3-week cycle.
• Drug Standard Chemotherapy
  All enrolled patients will receive study intervention starting on Day 1 of each 3-week cycle until disease progression, intolerable toxicity, or study withdrawal: standard chemotherapy based on anthracycline or gemcitabine once every 3 weeks (Q3W).

Primary outcome measures

• Objective Response Rate (ORR) [Time frame: From the date of first study treatment until disease progression or death from any cause, whichever occurs first, assessed up to 24months.]

Secondary outcome measures (7)

• Duration of Response (DoR) [Time frame: From the date of first documented response (complete response [CR] or partial response [PR]) to the time of disease progression or death from any cause, whichever occurs first, assessed up to 24months.]
• Progression-Free Survival (PFS) [Time frame: Through study completion, an average of 2 years.]
• Overall Survival (OS) [Time frame: Through study completion, an average of 2 years.]
• Disease Control Rate (DCR) [Time frame: From the date of first study treatment until disease progression or death from any cause, whichever occurs first, assessed up to 24 months.]
• Best Overall Response (BOR) [Time frame: Through study completion, average follow-up of 2 years.]
• Time to Response (TTR) [Time frame: From first dose until first confirmed response, assessed up to 48 months.]
• Adverse Events (AEs) [Time frame: From first study drug administration through 40 days after the last dose; overall average follow-up duration is 2 years.]

Eligibility criteria

Inclusion criteria

• Male or female patients aged ≥18 years.
• 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.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
• At least one measurable lesion at baseline according to RECIST 1.1 criteria.
• 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
• 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:

• Spinal cord compression, leptomeningeal disease, or clinically active central nervous system (CNS) metastases.
• Active primary immunodeficiency, known HIV infection, active hepatitis B virus (HBV) or hepatitis C virus (HCV) infection.
• 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.
• 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.
• Pulmonary criteria:

• 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);
• 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;
• Prior pneumonectomy.
• Poor compliance unable to cooperate with study treatment and procedures.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

N/A

Model

Single group

Masking

Open label

Primary purpose

Treatment

Study locations

Center list to be confirmed — check the primary protocol.

Identifiers

NCT: NCT07646080 · JY2026-036

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗