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.
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 Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
35
Toripalimab, 240mg, every 3 weeks until disease progress or intolerable toxicity
Cancer center of Sun Yat-sen University
Guangzhou, Guangdong, China
RECRUITINGObjective Response Rates (ORR)
the ratio of patients whose efficiency evaluation is CR or PR
Time frame: up to 2 years
Overall Survival (OS)
defined as the period from the first dose of study treatment to loss of follow-up or death
Time frame: up to 2 years
Progression free survival (PFS)
defined as the time from the first dose of study treatment to disease progression
Time frame: 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.
Time frame: up to 2 years
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