Toripalimab（JS001） as Monotherapy in Participants With POLE or POLD-1 Mutated and Non-MSI-H Advanced Solid Tumors

NCT03810339 | Recruiting Phase 2

• 1 other identifier: PPM
• Study Type: interventional
• Target: 35
• Locations: 1 country
• Sites: 4

Brief Summary

The purpose of this study is to evaluate the response of toripalimab (JS001), a PD1 antibody, in participants with POLE or POLD-mutated and non microsatellite instability (non-MSI-H) advanced solid cancers.

Conditions

Solid Tumor; Advanced Cancer

Keywords

Immune checkpoint inhibitor; POLE/POLD mutation; non-MSI-H

Outcome Measures

Primary Outcomes (1)

• Objective Response Rates (ORR)

  the ratio of patients whose efficiency evaluation is CR or PR

  up to 2 years

Secondary Outcomes (3)

• Overall Survival (OS)

  up to 2 years

• Progression free survival (PFS)

  up to 2 years

• Adverse Events (AEs)

  up to 2 years

Study Arms (1)

Toripalimab

EXPERIMENTAL

Toripalimab, 240mg, every 3 weeks until disease progress or intolerable toxicity

Drug: Toripalimab

Interventions

Toripalimab DRUG

Toripalimab, 240mg, every 3 weeks until disease progress or intolerable toxicity

Toripalimab

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Participants must provide written informed consent to participate
• Adult aged between 18 and 75 years old
• Participants with Histologically- or cytologically- proven advanced solid tumors and not responding to standard therapy
• MSS (microsatellite sability) or MSI-L (microsatellite instability-low) or pMMR status
• Germline mutations or somatic mutations in POLE or POLD (synonymous mutation is excluded)
• Patients refuse any conventional chemotherapy or targeted therapy
• Patients are willing to take biopsy of tumor tissue and take blood samples before treatment (blood samples are also taken at each time of therapeutic evaluation)
• Participants must have at least one measurable site of disease according to Response Evaluation Criteria in Solid Tumors (RECIST) criteria. Lesions previously treated with radiotherapy should not be regarded as target lesions unless there is a definite progression of the lesion after radiotherapy.
• Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1
• Estimated life expectancy is greater than 3 months
• Participants can provide more than 10 paraffin sections of tumor tissue
• No history of radiotherapy or received non-targeted radiotherapy outside the target lesions for this study more than 4 weeks ago before the first dose of study treatment
• Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5 x (5 x in participants with liver metastasis) upper limit of normal (ULN)
• Albumin ≥ 3 g/dL
• Alkaline phosphatase ≤ 2.5 x ULN.

You may not qualify if:

• Patients with confirmed or suspected brain metastases
• Patients with cancerous meningitis
• Patients without germline mutations or somatic mutations in POLE and POLD
• MSI-H (microsatellite instability-high) or dMMR
• Prior treatment with PD-1 inhibitors, PD-L1 inhibitors or CTLA-4 inhibitors (or other inhibitors in T cell co-stimulatory signals or checkpoint pathways)
• Known history or evidence of cytotoxic drug therapy, biologic drug therapy (such as monoclonal antibodies), immunotherapy (such as interleukin 2 or interferon), or other investigational drugs therapy in the 4 weeks before the first dose of study treatment
• Known history or evidence of significant immunodeficiency (including but not limited to: interstitial pneumonia, uveitis, enteritis, hepatitis, pituitary inflammation, nephritis, hyperthyroidism and hypothyroidism; Patients with vitiligo or asthma completely relieved can be included. Asthma that requires medical intervention cannot be included)
• Patients with a condition requiring systemic treatment with either corticosteroids (\> 10 mg daily prednisolone equivalent) or other immunosuppressive medications
• Patients with active tuberculosis. Known history of antituberculosis drugs treatment in 1 year before the first dose of study treatment
• Administration of an anti-infection vaccine (e.g. influenza vaccine, chickenpox vaccine) in the 4 weeks before the first dose of study treatment
• Symptomatic heart failure, coronary heart disease (CHD), myocardial infarction in the 6 months before the first dose of study treatment
• Known allergy to JS001 or its excipients
• Pregnant or breastfeeding females
• Other prior malignancy active within the previous 5 years except for non-melanoma skin cancer
• Persons without legal capacity

Sponsors & Collaborators

• Sun Yat-sen University: lead

Study Sites (4)

Cancer center of Sun Yat-sen University

Guangzhou, Guangdong, 510060, China

RECRUITING

The Affiliated Hospital of Guizhou Medical University

Guiyang, Guizhou, China

RECRUITING

Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology

Wuhan, Hubei, China

RECRUITING

The Second Affiliated Hospital of Dalian Medical University

Dalian, Liaoning, China

RECRUITING

MeSH Terms

Interventions

toripalimab

Study Officials

• Rui-hua Xu, MD, PhD

  Sun Yat-Sen University Cancer Center

  PRINCIPAL INVESTIGATOR

• FENG WANG, MD,PhD

  Sun Yat-Sen University Cancer Center

  PRINCIPAL INVESTIGATOR

• Ying Jin

  Sun Yat-Sen University Cancer Center

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Feng Wang, MD, PhD

CONTACT

+862087342635; wangfeng@sysucc.org.cn

YING JIN, MD

CONTACT

+862087342479; jinying1@sysucc.org.cn

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: President and Professor

Study Record Dates

• First Submitted: January 17, 2019
• First Posted: January 18, 2019
• Study Start: January 15, 2019
• Primary Completion (Estimated): January 15, 2028
• Study Completion (Estimated): December 31, 2029
• Last Updated: April 23, 2026

Record last verified: 2026-04

Locations

CN (4)