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.

Study Overview

• Status: Not yet recruiting
• Conditions: Dermatofibrosarcoma Protuberans (DFSP)
• Intervention / Treatment: Drug: Toripalimab; Drug: Anlotinib; Drug: Standard Chemotherapy

• Study Type: Interventional
• Enrollment (Estimated): 20
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Haihua Yuan; Phone Number: +86-021-56691101-7261; Email: ayuan790415@shsmu.edu.cn

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Toripalimab, Anlotinib Hydrochloride Combined with 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: Toripalimab 240 mg (fixed dose) administered intravenously once every 3 weeks (Q3W); Anlotinib 10 mg administered orally once daily on Days 1-14 of each 3-week cycle; and standard chemotherapy based on anthracycline or gemcitabine once every 3 weeks (Q3W).

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).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective Response Rate (ORR)	The Objective Response Rate (ORR) is defined as the percentage of patients whose best response on or before the first occurrence of disease progression is a complete response (CR) or partial response (PR). Tumor responses were assessed by investigators using Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1.	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

Outcome Measure	Measure Description	Time Frame
Duration of Response (DoR)	Duration of Response (DoR) is defined as the time from the date of first documented response (CR or PR) to date of first occurrence of disease progression as determined by the investigator, or death from any cause, whichever occurs first.	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)	Progression-Free Survival (PFS) is defined as the time from the start of study treatment to the first occurrence of disease progression, or death, whichever occurs first. Tumor responses were assessed by investigators using RECIST version 1.1.	Through study completion, an average of 2 years.
Overall Survival (OS)	Overall Survival (OS) is defined as the time from the date of the first study treatment (Day 1) to the date of death from any cause.	Through study completion, an average of 2 years.
Disease Control Rate (DCR)	Disease Control Rate (DCR) is defined as the proportion of patients whose best response is CR, PR or SD maintained more than 8 weeks. Tumor responses were assessed by investigators using RECIST version 1.1.	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)	Best overall response (BOR) is defined as the best tumor response achieved at any time during treatment, categorized as Complete Response (CR), Partial Response (PR), Stable Disease (SD), or Progressive Disease (PD) per RECIST 1.1 criteria. Responses require confirmation at least 4 weeks later.	Through study completion, average follow-up of 2 years.
Time to Response (TTR)	Time to response (TTR) is defined as the time from the date of first study drug administration to the date of first documented and confirmed CR or PR per RECIST 1.1.	From first dose until first confirmed response, assessed up to 48 months.
Adverse Events (AEs)	Incidence, severity (graded per NCI CTCAE version 5.0), and causality of adverse events (AEs). Special attention will be paid to AEs of special interest associated with toripalimab, anlotinib, and anthracycline- or gemcitabine-based chemotherapy, including myelosuppression, hypertension, diarrhea, rash, liver function abnormalities, endocrine disorders, and cardiac toxicity (monitored via periodic left ventricular ejection fraction and electrocardiography).	From first study drug administration through 40 days after the last dose; overall average follow-up duration is 2 years.

Collaborators and Investigators

• Sponsor: Yanjie Zhang, MD

Study record dates

Study Major Dates

• Study Start (Estimated): June 15, 2026
• Primary Completion (Estimated): December 31, 2028
• Study Completion (Estimated): December 31, 2029

Study Registration Dates

• First Submitted: April 14, 2026
• First Submitted That Met QC Criteria: June 9, 2026
• First Posted (Actual): June 12, 2026

Study Record Updates

• Last Update Posted (Actual): June 12, 2026
• Last Update Submitted That Met QC Criteria: June 9, 2026
• Last Verified: June 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms; Neoplasms by Histologic Type; Sarcoma; Neoplasms, Connective and Soft Tissue; Neoplasms, Connective Tissue; Fibrosarcoma; Neoplasms, Fibrous Tissue; Dermatofibrosarcoma; anlotinib; toripalimab
• Other Study ID Numbers: JY2026-036

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No