Avelumab in Third-Line Gastric Cancer (JAVELIN Gastric 300)
Condition: Unresectable, Recurrent, Locally Advanced or Metastatic Gastric or Gastroesophageal Junction Adenocarcinoma; Gastric Cancer Third Line
MeSH terms: Adenocarcinoma; Stomach Neoplasms; Esophageal Neoplasms
Intervention: Avelumab; Irinotecan; Paclitaxel; Best Supportive Care (BSC)
Intervention description: Avelumab was administered as a 1-hour intravenous (IV) infusion at 10 milligram per kilogram (mg/kg) once every 2-week treatment cycle until confirmed progressive disease or unacceptable toxicity along with best supportive care (BSC).; Irinotecan was administered at a dose of 150 mg/m ^2 on Day 1 and 15 of a 4-week treatment cycle until disease progression or unacceptable toxicities along with BSC.; Paclitaxel was administered at a dose of 80 mg/m^2 on Day 1, 8, and 15 of a 4-week treatment cycle until disease progression or unacceptable toxicities along with BSC.; BSC is defined as treatment administered with the intent to maximize Quality of life without a specific antineoplastic regimen and is based on investigator's discretion. BSC was administered once every 3 weeks.
Intervention MeSH terms: Paclitaxel; Irinotecan; Avelumab
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 371.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Avelumab; Gastric cancer; Gastroesophageal junction adenocarcinoma

Summary:

      The purpose of this study was to demonstrate superiority of treatment with avelumab plus best
      supportive care (BSC) versus physician's choice (chosen from a pre-specified list of
      therapeutic options) plus BSC.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Male or female subjects aged greater than or equal to (>=) 18 years

          -  Subjects with histologically confirmed recurrent unresectable, recurrent locally
             advanced or metastatic adenocarcinoma of the stomach or gastroesophageal junction
             (GEJ)

          -  Availability of a formalin-fixed, paraffin-embedded (FFPE) block containing tumor
             tissue

          -  Subjects must have received 2 prior courses of systemic treatment for unresectable,
             recurrent, locally advanced or metastatic gastric cancer, and must have progressed
             after the second line

          -  Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 to 1 at trial
             entry

          -  Adequate hematological, hepatic and renal functions defined by the protocol

          -  Negative blood pregnancy test at Screening for women of childbearing potential.

          -  Highly effective contraception for both male and female subjects if the risk of
             conception exists

        Other protocol defined inclusion criteria could apply

        Exclusion Criteria:

          -  Prior therapy with any antibody or drug targeting T-cell coregulatory proteins

          -  Concurrent anticancer treatment

          -  Major surgery

          -  Subjects receiving immunosuppressive agents (such as steroids) for any reason should
             be tapered off these drugs before initiation of the trial treatment (with the
             exception of subjects with adrenal insufficiency, who may continue corticosteroids at
             physiologic replacement dose, equivalent to less than [<] 10 mg prednisone daily).

          -  All subjects with brain metastases, except those meeting the following criteria: a.
             Brain metastases have been treated locally, and b. No ongoing neurological symptoms
             that are related to the brain localization of the disease (sequelae that are a
             consequence of the treatment of the brain metastases are acceptable)

          -  Previous malignant disease (other than gastric cancer) within the last 5 years with
             the exception of basal or squamous cell carcinoma of the skin or carcinoma in situ
             (bladder,cervical, colorectal, breast)

          -  Prior organ transplantation, including allogeneic stem-cell transplantation
             Significant acute or chronic infections

          -  Active autoimmune disease that might deteriorate when receiving an immunostimulatory
             agent

          -  Known severe hypersensitivity reactions to monoclonal antibodies, any history of
             anaphylaxis, or uncontrolled asthma (that is, 3 or more features of partially
             controlled asthma)

          -  Persisting toxicity of grade >2 related to prior therapy except neuropathy and
             alopecia

          -  Neuropathy Grade greater than or equal (>=) 3.

          -  Pregnancy or lactation

          -  Known alcohol or drug abuse

          -  History of uncontrolled intercurrent illness including hypertension, active infection,
             diabetes

          -  Clinically significant (i.e., active) cardiovascular disease

          -  All other significant diseases might impair the subject's tolerance of trial treatment

          -  Any psychiatric condition that would prohibit the understanding or rendering of
             informed consent and that would limit compliance with study requirements

          -  Vaccination within 4 weeks of the first dose of avelumab and while on trial is
             prohibited except for administration of inactivated vaccines

          -  Legal incapacity or limited legal capacity

          -  Subjects will be excluded from the treatment with irinotecan or paclitaxel monotherapy
             if administration of their chemotherapy would be inconsistent with the current local
             labeling (for example, in regard to contraindications, warnings/precautions, or
             special provisions) for that chemotherapy. Investigators should check updated labeling
             via relevant websites before randomization

          -  Subjects should start treatment administration within 28 days after signing the
             informed consent form (ICF). Treatment administration will start within 4 days after
             the randomization call