This is a Phase Ib/II study to identify the recommended dose of paclitaxel and nivolumab for further study, and to assess the safety and clinical efficacy of this combined treatment in EBV-related, MSI-high, or PD-L1 positive advanced gastric cancer after first line treatment.
This is a Phase Ib/II study to identify the recommended dose of paclitaxel and nivolumab for further study, and to assess the safety and clinical efficacy of this combined treatment in EBV-related, MSI-high, or PD-L1 positive advanced gastric cancer after first line treatment. Patients who are EBV-related, MSI-high, or PD-L1 positive will be confirmed by immunohistochemistry (IHC) in a central laboratory (Yonsei Cancer Center), and who meet all eligibility criteria will be enrolled to this study and receive treatment with nivolumab and paclitaxel until progressive disease is confirmed or at least 1 discontinuation criterion is met. It was assumed that about 15% of screened patients will be categorized EBV-related, MSI-high, or PD-L1 positive gastric cancer based on previously reported study results. Part 1\>\> Phase Ib Phase Ib: 6-12 (The actual number of subjects will be determined by the number of dose escalations to identify MTD and RP2D) Part 2\>\> Phase II - At the RP2D dose level in phase I part, we will expand phase 2 study for a total of 50 patients. Patients will be treated until the time of disease progression, intolerable toxicities, patient's refusal or consent withdrawal. Tumor assessment will be done every 6 weeks.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
50
Increasing dose levels of paclitaxel (70 mg/m2 or 80 mg/m2 on Days 1, 8 and 15 of a 28-day treatment cycle) in combination with a fixed dose of nivolumab (3 mg/kg on Days 1 and 15 of a 28-day treatment cycle) will be explored using a 3+3 design to evaluate the safety and tolerability and to determine a MTD.
Yonsei University Health System, Severance Hospital
Seoul, South Korea
(Phase Ib) Maximum Tolerated dose (MTD)
Maximum Tolerated dose (MTD) as determined by Dose limiting Toxicity (DLT).
Time frame: 424 weeks
(Phase Ib) Recommended phase 2 dose
Recommended phase 2 dose as determined by Dose limiting Toxicity (DLT).
Time frame: 424 weeks
(Phase II) PFS
Progression-free survival (PFS): Defined as the time from start of study treatment until the date of objective disease progression or death (by any cause in the absence of disease progression) Progression is defined in accordance with the RECIST v1.1 criteria. PFS is defined as the interval between the date of first dose and the earliest date of disease progression or death due to any cause.
Time frame: 424 weeks
OS
Overall Survival (OS): the time from the date of first dose and the date of death from any cause
Time frame: 24 weeks
ORR
Overall response rate (ORR): defined as the percentage of subjects with a confirmed CR or PR per RECIST v1.1 relative to the total number of subjects
Time frame: 24 weeks
DCR
Disease Control Rate (DCR): the proportion of randomized patients achieving a best overall response of CR, PR, or SD.
Time frame: 24 weeks
PFS
Progression-free survival (PFS): To evaluate the treatment effect of nivolumab and paclitaxel on progression-free survival (PFS) rate at 24 weeks
Time frame: 24 weeks
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