Kurzfassung

This is a multicenter, international, randomized, open-label Phase III trial of avelumab in subjects with advanced (unresectable, locally advanced or metastatic) adenocarcinoma of the stomach, or of the gastro-esophageal junction (GEJ) who are treatment naïve and have not yet received chemotherapy for the treatment of metastatic or locally advanced disease.
This study includes a screening period, Induction Phase, Maintenance Phase, and Follow-up Phase
Approximately 629 subjects will receive...This is a multicenter, international, randomized, open-label Phase III trial of avelumab in subjects with advanced (unresectable, locally advanced or metastatic) adenocarcinoma of the stomach, or of the gastro-esophageal junction (GEJ) who are treatment naïve and have not yet received chemotherapy for the treatment of metastatic or locally advanced disease.
This study includes a screening period, Induction Phase, Maintenance Phase, and Follow-up Phase
Approximately 629 subjects will receive induction chemotherapy comprised of oxaliplatin and either 5-FU or capecitabine (Induction Phase) for 12 weeks. Approximately 440 subjects who experience a complete response (CR), partial response (PR), or stable disease (SD) will enter the Maintenance Phase and be randomized to receive either avelumab, or continuation of the same chemotherapy regimen from the Induction Phase (Maintenance Phase).
The dose and schedule of the chemotherapy during the Induction Phase are as follows:
Oxaliplatin at 85 mg/m2 IV on Day 1 with 5-FU at 2600 mg/m2 IV continuous infusion over 24 hours on Day 1 plus leucovorin 200 mg/m2 IV on Day 1, given every 2 weeks (for up to 12 weeks)OR
Oxaliplatin at 130 mg/ m2 IV on Day 1 with capecitabine at 1000 mg/m2, twice daily for 2 weeks followed by a 1-week rest period given every 3 weeks (for up to 12 weeks)Upon completion of chemotherapy in the Induction Phase, subjects without disease progression (subjects with SD, PR, or CR) will be eligible for randomization to the Maintenance Phase where they will receive either avelumab, or continue the same regimen of chemotherapy from the Induction Phase.
Treatment during the Maintenance Phase are as follows:
For subjects randomized to avelumab: avelumab will be given at a dose of 10 mg/kg as a 1 hour IV infusion once every 2 weeks
For subjects randomized to chemotherapy: continuation of the same regimen of oxaliplatin-fluoropyrimidine doublet as in the Induction Phase for 2 additional cycles:

Upon completion of the oxaliplatin-fluoropyrimidine doublet during the Maintenance Phase, all patients will continue to receive Best Supportive Care (BSC)
Patients may receive S1 monotherapy as maintenance after the 2 cycles of oxaliplatin-fluoropyrimidine doublet as long as S1 monotherapy is approved for use as Standard of Care (SOC) at the investigator’s institution
For patients receiving chemotherapy dose modifications after the starting dose are allowed if the continuation of the oxaliplatin-fluoropyrimidine doublet is prohibited by toxicityFor subjects receiving avelumab, treatment may continue past the initial determination of disease progression per RECIST version 1.1 as long the following criteria are met:
Investigator-assessed clinical benefit, without any rapid disease progression
Tolerance of trial treatment
Stable Eastern Cooperative Oncology Group (ECOG) performance status (PS=0 or 1)
Treatment beyond progression will not delay an imminent intervention to prevent serious complications of disease progression (for example, central nervous system metastases).Subjects receiving avelumab who have experienced a CR should be treated for a minimum of 12 months and/or until disease progression or unacceptable toxicity, after confirmation of response.
Subjects in the Maintenance Phase will receive trial treatment until progressive disease (PD) per RECIST v1.1, significant clinical deterioration (clinical progression), unacceptable toxicity, withdrawal of consent, or if any  criterion for withdrawal from the trial or trial treatment is fulfilled.» weiterlesen» einklappen