Included blood draws for clinical assessments.

To update the Investigation New Drug (IND) number. To change the medical responsible for the trial. To modify exclusion criteria for persisting toxicity related to prior therapy according to the National Cancer Institute-Common Terminology Criteria for Adverse Event (NCI-CTCAE) v4.03 criteria. To make minor changes to clarify the schedule of assessments and text for evaluation of radiographic scans. To clarify the role of the Independent Review Committee (IRC) and independent radiologist. To revise the protocol to include epirubicin as an acceptable regimen for the first-line treatment of metastatic, recurrent, or unresectable gastric cancer. To clarify that all prior adjuvant and neo-adjuvant treatments are allowed. To exclude subjects with active tuberculosis from the study. To modify contraceptive measures to include Clinical Trials Facilitation Group (CTFG) recommendations related to contraception and pregnancy testing in clinical trials. To correct a minor typographical error.

To amend the trial schedule to have an End of Treatment Visit within 7 days of the decision to discontinue, a Safety Follow-up Visit 30 days after last treatment (±5 days), a Safety Follow-up Phone Call 90 days after last treatment (±1 week), and the Long-Term Follow-up every 12 weeks after last treatment (±2 weeks). The reporting of AEs and concomitant medications/procedures was also updated in line with the new schedule. To reduce the frequency of pregnancy testing to every 4 weeks prior to Week 13. To remove the measurement of antinuclear antibody (ANA), antineutrophil cytoplasmic antibodies (ANCA), rheumatoid factor (RF) and adrenocorticotropic hormone (ACTH) from laboratory sampling. To remove the collection of blood samples for PK determination at 2 to 8 hours post-infusion, and at the end of the infusion for both Week 13 and every 12 weeks until progression. To remove the collection of blood samples for soluble factors at 2 to 8 hours post-infusion. To remove the collection of blood samples at the End of Treatment Visit for HAHA (immunogenicity) analysis. To reduce the frequency of tumor evaluation/staging by Computed Tomography (CT) scan/Magnetic Resonance Imaging (MRI)/other established methods to every 12 weeks after the first 12 months. To add the collection of samples for soluble factors, gene expression profiling and biomarkers at Week 1 for the comparator treatment arms. To collect core serum chemistry samples rather than full serum chemistry samples during the treatment phase, and collect additional parameters for core serum chemistry (amylase, lipase, lactate dehydrogenase and creatine kinase).

To add management guidelines for cardiac irAEs. To update the sponsor’s medical responsible and global program lead. To clarify the monitoring of SAEs that are ongoing at the 30-day Safety Follow-up visit. To provide the clinical trial registry number. To correct a typographical error in the Schedule of Assessments and to replace the terminology of human anti-human antibody (HAHA) with ADA. To make minor editorial corrections to abbreviations and the use of “patient” and “subject.”

Revise the time point of the primary analysis to occur after a minimum of 6 months follow-up since the last subject randomized. Correct a discrepancy between sections in the acceptable regimens for first-line treatment. Clarify the definition of second-line therapy with the respect to another line of a platinum-based treatment or FOLFIRI. Update the requirements for premedication and mandatory discontinuation. Clarify that Pharmacokinetics (PK) and Anti-drug Antibody (ADA) samples collected at the same time point can be used interchangeably. Clarify the definition and censoring rules for duration of response. Update the background information for avelumab. Clarify the treatment of subjects who continue avelumab plus Best Supportive Care (BSC) beyond progression. Update the guidelines for management of Immune-related Adverse Event (irAEs). Update the Sponsor’s medical responsible. Clarify the monitoring of Serious Adverse Events (SAEs) that are ongoing at the 30-day Safety Follow-up visit. Update the contact information for the senior expert statistician.

To change the follow-up time such that subjects who discontinue treatment will no longer be followed for disease progression of survival. Provided subjects additional treatment options.