Pancreatic cancer is a kind of digestive system tumor with extremely high malignancy and poor prognosis. Although the trend of benefit from immunotherapy in combination with chemotherapy is currently reflected in several exploratory studies, the overall efficacy is still relatively limited.
Dysregulation of epigenetic mechanisms, which is common in cancer, leads to down-regulation of genes involved in tumor antigen processing or presentation, resulting in immune evasion and thus affecting the efficacy of immunotherapy. Epigenetic inhibitors may enhance the efficacy of immunotherapy by enhancing antigenicity and presentation of tumor-associated antigens, reprogramming the tumor microenvironment to counteract immunosuppression, and reversing cytotoxic T-cell depletion. Thus, decitabine-promoted immunotherapeutic sensitization is a potential therapeutic avenue for mPDAC patients that warrants further exploration in clinical trials. Taking into account the characteristics of pancreatic cancer immunophenotype, exploring combination therapy regimens that enhance anti-tumor immune response and improve the efficacy of immunotherapy has become an urgent clinical problem.
This study is a prospective, single-arm, single-center, phase IB/II clinical study exploring the efficacy and safety of adebrelimab in combination with decitabine, albumin-bound paclitaxel, and gemcitabine in the first-line treatment of metastatic pancreatic cancer. The primary study endpoints are DLT, RP2D and ORR. Secondary study endpoints are OS, PFS, DCR, DoR and safety.
Neutrophils ≥1.5*109/L; platelets ≥80*109/L; hemoglobin ≥9g/dl; serum albumin ≥3g/dl;
Total bilirubin ≤ 1.5 times the upper limit of normal value (biliary obstruction allows biliary drainage); ALT and AST ≤ 3 times the upper limit of normal value (for patients with hepatic metastases, it can be relaxed to ≤ 5 times the upper limit of normal value);
Serum creatinine ≤1.5 times the upper limit of normal value, creatinine clearance ≥50ml/min;
INR ≤1.5 times the upper limit of normal value and APTT ≤1.5 times the upper limit of normal value (for the use of a stable dose of anticoagulation therapy, such as low molecular heparin or warfarin, and the INR is within the expected therapeutic range of anticoagulants can be screened);
patients with pancreatic cancer originating from non-pancreatic ductal epithelium, including pancreatic neuroendocrine carcinoma, pancreatic follicular cell carcinoma, pancreatoblastoma, and solid-pseudopapillary tumors;
patients with known central nervous system metastases;
severe gastrointestinal dysfunction (with bleeding, obstruction; inflammation greater than grade 2; diarrhea greater than grade 1);
the presence of third interstitial fluid (e.g., massive pleural fluid) that could not be stabilized (without interventional therapy after drain removal) except for ascites within 2 weeks before randomization;
Single group
Adebrelimab;decitabine;
DrugAdebrelimab:1200 mg Decitabine:10mg/m2 or 15mg/m2
Dose Limiting Toxicity (DLT)
Any adverse event of a certain observation period (within 28 days of the first dose) that is related to the study medication and meets a CTCAE of grade 3 or higher
The recommended phase 2 dose (RP2D)
The recommended phase 2 dose
Objective Response Rate (ORR)
The objective response rate is estimated by the proportion (percentage) of participants with the best response of complete response (CR), or partial response (PR) by RECIST 1.1 criteria
Overall Survival (OS)
Overall Survival (OS) (median) was determined using the number of months measured from the initial date of treatment to the recorded date of death of participants.
Progression-free Survival (PFS)
Progression-free Survival (PFS) (median) was determined using the number of months measured from the initial date of treatment to the date of documented progression, or the date of death (in the absence of progression) of participants.
Disease Control Rate (DCR)
The objective response rate is estimated by the proportion (percentage) of participants with the best response of complete response (CR), partial response (PR) and stable disease(SD) by RECIST 1.1 criteria
During of response (DoR)
Estimated by the proportion (percentage) of participants with the time from the first recording of tumor remission (i.e., CR or PR, according to the appropriate criteria) to the first recording of disease progression (PD, according to the appropriate criteria) or death from any cause, whichever occurs first.
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