A Phase 1b, open-label, multicenter, dose escalation and dose expansion study of S-1 in combination with nab-paclitaxel and gemcitabine (GAS) in subjects with metastatic pancreatic adenocarcinoma. This study is a dose escalation and dose expansion study with the objective to establish the MTD and/or RP2D and/or DLT of nab-paclitaxel and gemcitabine in combination with a body surface area(BSA)-based dose of S-1 in subject with metastatic pancreatic adenocarcinoma.
Histologically or cytologically confirmed pancreatic adenocarcinoma (poorly differentiated carcinoma is allowed in the absence of neuroendocrine features or squamous differentiation)
Treatment-naï ve stage IV disease (measurable disease is required). Prior adjuvant chemotherapy or radiochemotherapy is allowed, if completed ≥ 6 months before enrollment.
Measurable disease defined as at least one lesion that can be measured in at least one dimension (longest diameter to be recorded) as ≥ 10 mm with CT scan or MRI
Eastern Cooperative Oncology Group (ECOG) performance score of 0-1
Have known endocrine pancreatic tumors or ampullary cancer
Have received first line treatment for metastatic pancreatic cancer
Have a serious concomitant active infection or other major comorbidities that, in the opinion of the investigator, would compromise the patient's ability to adhere to the protocol (e.g., stroke, uncontrolled arrhythmia, heart failure, or active autoimmune disease)
Have HIV history or hepatitis B and C infection, except for prescribing anti-hepatitis B medications for hepatitis B carrier and undetectable HCV RNA level for hepatitis C prior to enrollment.
Sequential
Gemcitabine 800mg/m2 + Nab-paclitaxel 100mg/m2 + S-1 (dose according to BSA)
Combination productDose escalation study-dose level 1
Gemcitabine 800mg/m2 + Nab-paclitaxel 125mg/m2 + S-1 (dose according to BSA)
Combination productDose escalation study-dose level 2
Gemcitabine 1000mg/m2 + Nab-paclitaxel 125mg/m2 + S-1 (dose according to BSA)
Combination productDose escalation study-dose level 3
Maximum tolerated dose (MTD)
To determine a recommended Phase 2 dose (RP2D) of nab-paclitaxel and gemcitabine in combination with body surface area (BSA) - based dose of S-1 in subject with metastatic pancreatic adenocarcinoma
Dose-limiting toxicity (DLT)
Objective response rate (ORR)
Tumor response will be evaluated according to the Response Evaluation Criteria Solid Tumors (RECIST) criteria version 1.1.
Safety profile of GAS regimen
Safety profile will be recorded and graded according to NCI-CTCAE v 5.0.
Disease Control Rate (DCR)
Defined as having complete response, partial response or stable disease at 12 weeks. (based on RECIST Version 1.1)
Duration of Response (DoR)
Time from documentation of tumor response to disease progression. (based on RECIST Version 1.1)
Progression-free Survival (PFS)
From the start date of study treatment to the date of progression disease or death. (based on RECIST Version 1.1)
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