Solid TumorPhase 2NCT03810339
Toripalimab（JS001） as Monotherapy in Participants With POLE or POLD-1 Mutated and Non-MSI-H Advanced Solid Tumors
A Phase 2 study testing Toripalimab in people with Solid Tumor and Advanced Cancer, run by Sun Yat-sen University at 4 sites in China.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Solid Tumor, Advanced Cancer
- What is being tested?
- Toripalimab
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 35 participants
- Where
- 4 sitesChina
- Study dates
- 15 Jan 2019to 31 Dec 2029
- Phase
- Phase 2
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
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- 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.
- Serum bilirubin <1.5 mg/dL
- Creatinine ≤ ULN.
- Absolute neutrophil count ≥ 1.5X10E9/L
- Platelets ≥ 100 x 10E9/L
- Hemoglobin ≥ 90 g/L
- For females of childbearing potential (defined as <2 years after last menstruation or not surgically sterile), a negative serum pregnancy test must be performed within 21 days of the first dose of study treatment.
- For females: agreement to contraception during the study treatment period and for at least 28 days after the last dose of study treatment
Who cannot join
- 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
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- 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
- Positive test for HIV or AIDS
- Positive test for HbsAg and HBV-DNA copy numbers (≥ 1000cps/ml)
- Positive test for HCV
- Any medical disorder or condition that, in the opinion of the investigator, may affect the compliance or the signing of informed consent, etc.
Trial locations and contacts
4 sites in 1 country. Contact the study team or a site near you to ask about taking part.
China4 sites, 4 recruiting
- Recruiting
The Second Affiliated Hospital of Dalian Medical University
Dalian, Liaoning
Jinghua Sun, M.D., +86 0411-84671291, sunjinghua2008@hotmail.com
- Recruiting
Cancer center of Sun Yat-sen University
Guangzhou, Guangdong, 510060
Zhi-da Lv, BS, +862087342635, lvzd@sysucc.org.cn
Rui-hua Xu, MD, PhD
- Recruiting
The Affiliated Hospital of Guizhou Medical University
Guiyang, Guizhou
WeiWei Chen, M.D., +86 085186512900, 33054905@qq.com
- Recruiting
Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology
Wuhan, Hubei
Liu Huang, M.D., 027-69378822, huangliu017@163.com
About this study
Official title: A Phase II Open Label Study of Toripalimab, a PD-1 Antibody, in Participants With POLE or POLD-1 Mutated and Non-MSI-H Advanced Solid Tumors
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.
Read the detailed description
Immune checkpoint inhibitor (ICI) therapy including antibodies targeting PD-1/PD-L1 or CTLA-4 has greatly advanced the cancer treatments. Recent studies have identified several predictive markers for ICI which includes microsatellite instability (MSI), PD-L1 expression and tumor mutation burden (TMB). DNA polymerase epsilon (POLE) and delta (POLD) are in charge of DNA replication as well as proofreading during DNA replication. Their germline or somatic mutations can lead to DNA repair deficiencies and carcinogenesis. The investigators has found that the POLE or POLD mutation causes an increased TMB in cancer patients and may lead to a better survival to ICI. Therefore, the purpose of this study is to evaluate the efficacy of toripalimab , a PD1 antibody, in participants with POLE or POLD-mutated and non microsatellite instability high (non-MSI-H) advanced solid cancers. This is a Phase II, open label, single arm study. Participants enrolled in this study received toripalimab 240mg, every 3 weeks until disease progress or intolerable toxicity. Primary endpoints is ORR and secondary endpoints are OS, PFS and safety.
- Conditions
- Solid Tumor, Advanced Cancer
- Being tested
- Toripalimab
- Keywords
- Immune checkpoint inhibitor, POLE/POLD mutation, non-MSI-H
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ToripalimabDrug
Toripalimab, 240mg, every 3 weeks until disease progress or intolerable toxicity
| Study group | Role | What they receive |
|---|---|---|
| Toripalimab | Experimental | Toripalimab, 240mg, every 3 weeks until disease progress or intolerable toxicity Receives: Drug: Toripalimab |
What is being measured
The primary outcome is the main question the study is designed to answer.
Objective Response Rates (ORR)
the ratio of patients whose efficiency evaluation is CR or PR
Measured: up to 2 years
Secondary outcomes (3)
Overall Survival (OS)
defined as the period from the first dose of study treatment to loss of follow-up or death
Measured: up to 2 years
Progression free survival (PFS)
defined as the time from the first dose of study treatment to disease progression
Measured: up to 2 years
Adverse Events (AEs)
All treatment-related adverse events (AEs) were categorized according to the National Cancer Institute's Common Terminology Criteria for Adverse Events.
Measured: up to 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Jan 2019
- Study start15 Jan 2019
- Primary completion15 Jan 2028 (estimated)
- Study completion31 Dec 2029 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Solid TumorStudies of the same condition, open and under way.
- More trials run by Sun Yat-sen UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 35 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Sun Yat-sen University
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Rui-hua Xu, MD, PhD, Sun Yat-sen University
- Investigators
- Rui-hua Xu, MD, PhD, Principal investigator, Sun Yat-Sen University Cancer CenterFENG WANG, MD,PhD, Principal investigator, Sun Yat-Sen University Cancer CenterYing Jin, Principal investigator, Sun Yat-Sen University Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03810339
- Sponsor's protocol ID
- PPM
- Status last verified
- Apr 2026
- First submitted
- 17 Jan 2019
- Last updated
- 23 Apr 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 23 Apr 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase II Open Label Study of Toripalimab, a PD-1 Antibody, in Participants With POLE or POLD-1 Mutated and Non-MSI-H Advanced Solid Tumors
- ClinicalTrials.gov ID
- NCT03810339
- Acronym / sponsor ID
- PPM
- Conditions
- Solid Tumor, Advanced Cancer
- Keywords
- Immune checkpoint inhibitor, POLE/POLD mutation, non-MSI-H
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 35 participants (estimated)
- Lead sponsor
- Sun Yat-sen UniversityUniversity, hospital or other
- Study start
- 15 Jan 2019 (actual)
- Primary completion
- 15 Jan 2028 (estimated)
- Study completion
- 31 Dec 2029 (estimated)
- First posted
- 18 Jan 2019 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
Immune checkpoint inhibitor (ICI) therapy including antibodies targeting PD-1/PD-L1 or CTLA-4 has greatly advanced the cancer treatments. Recent studies have identified several predictive markers for ICI which includes microsatellite instability (MSI), PD-L1 expression and tumor mutation burden (TMB). DNA polymerase epsilon (POLE) and delta (POLD) are in charge of DNA replication as well as proofreading during DNA replication. Their germline or somatic mutations can lead to DNA repair deficiencies and carcinogenesis. The investigators has found that the POLE or POLD mutation causes an increased TMB in cancer patients and may lead to a better survival to ICI. Therefore, the purpose of this study is to evaluate the efficacy of toripalimab , a PD1 antibody, in participants with POLE or POLD-mutated and non microsatellite instability high (non-MSI-H) advanced solid cancers. This is a Phase II, open label, single arm study. Participants enrolled in this study received toripalimab 240mg, every 3 weeks until disease progress or intolerable toxicity. Primary endpoints is ORR and secondary endpoints are OS, PFS and safety.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Toripalimab | Experimental | Drug: ToripalimabToripalimab, 240mg, every 3 weeks until disease progress or intolerable toxicity |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (22 listed)
- 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)
Key exclusion criteria (19 listed)
- 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)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| ToripalimabToripalimab, 240mg, every 3 weeks until disease progress or intolerable toxicity | Drug | Toripalimab |
Primary outcome
Objective Response Rates (ORR)
Time frame: up to 2 years
the ratio of patients whose efficiency evaluation is CR or PR
3 secondary outcomes
Overall Survival (OS)
Time frame: up to 2 years
Progression free survival (PFS)
Time frame: up to 2 years
Adverse Events (AEs)
Time frame: up to 2 years
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 23 Apr 2026.
- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Rui-hua Xu, MD, PhD principal investigator
Sun Yat-Sen University Cancer Center
FENG WANG, MD,PhD principal investigator
Sun Yat-Sen University Cancer Center
Ying Jin principal investigator
Sun Yat-Sen University Cancer Center
4 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Toripalimab in people with Solid Tumor and Advanced Cancer, run by Sun Yat-sen University at 4 sites in China.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 22 inclusion and 19 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 23 Apr 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 4 sites in China. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Feng Wang, MD, PhD (+862087342635, wangfeng@sysucc.org.cn), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Objective Response Rates (ORR) (time frame: up to 2 years). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 23 Apr 2026.