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
Overview
- Phase
- Phase 2
- Intervention
- Toripalimab
- Conditions
- Solid Tumor
- Sponsor
- Sun Yat-sen University
- Enrollment
- 35
- Locations
- 5
- Primary Endpoint
- Objective Response Rates (ORR)
- Status
- Recruiting
- Last Updated
- 9 days ago
Overview
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.
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.
Investigators
Rui-hua Xu, MD, PhD
President and Professor
Sun Yat-sen University
Eligibility Criteria
Inclusion Criteria
- •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
Exclusion Criteria
- •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
Arms & Interventions
Toripalimab
Toripalimab, 240mg, every 3 weeks until disease progress or intolerable toxicity
Intervention: Toripalimab
Outcomes
Primary Outcomes
Objective Response Rates (ORR)
Time Frame: up to 2 years
the ratio of patients whose efficiency evaluation is CR or PR
Secondary Outcomes
- Progression free survival (PFS)(up to 2 years)
- Overall Survival (OS)(up to 2 years)
- Adverse Events (AEs)(up to 2 years)