• Written informed consent and HIPAA authorization for release of personal health information prior to registration. NOTE: HIPAA authorization may be included in the informed consent or obtained separately.

• Age ≥ 18 years at the time of consent.

• ECOG Performance Status (PS) of 0-1within 28 days prior to registration. NOTE: Within 0-3 days prior to the anticipated C1D1, ECOG PS must be 0-1.

• Tumor tissue must be obtained from a biopsy performed either (a) prior to registration or (b) prior to C1D1, as described below.

‣ Prior to registration: if a biopsy was performed prior to registration and no interval systemic anti-cancer treatment was administered between the biopsy collection and C1D1, part of that tissue is required for correlative analysis, and must be identified during screening and shipped after registration. In this situation, tissue from a new biopsy is not required.

⁃ Prior to C1D1: For all other subjects, a new biopsy prior to C1D1 is required (research biopsy per parallel biopsy protocol entitled: Exploration of tumor biology in patients with metastatic esophageal and gastric cancer, \[biorepository protocol for prospective tissue collection\]) to obtain tissue.

⁃ NOTE: If tissue cannot be obtained by either of the above approaches (e.g., clinically contraindicated), the subject is not eligible for trial participation.

• Willingness to provide tissue and blood samples for correlative research purposes and presence of a malignant lesion that is amenable to repeat biopsy while on study protocol (e.g., primary tumor that can be accessed by EGD).

⁃ -NOTE: Enrollment in parallel biopsy protocol, if open for enrollment, is required. Parallel biopsy protocol entitled: Exploration of tumor biology in patients with metastatic esophageal and gastric cancer (biorepository protocol for prospective tissue collection).

• PD-L1 results are required, if available. If PD-L1 testing has not been done, it should be ordered as standard of care prior to C1D1. PD-L1 testing must be performed by a CLIA certified lab using the Dako 22C3 antibody.

• Histologically or cytologically proven adenocarcinoma of the stomach or GEJ.

• Metastatic, recurrent, or locally advanced unresectable disease.

• Candidate for pembrolizumab, ramucirumab, and paclitaxel (or nab-paclitaxel)

• Demonstrate adequate organ function as defined in the table below. All screening labs to be obtained within 28 days prior to registration. NOTE: Labs must also be obtained within 10 days prior to C1D1 treatment.

‣ Absolute Neutrophil Count (ANC) ≥ 1,100/mm3

⁃ Hemoglobin (Hgb) ≥ 8.5 g/dL without transfusion or EPO dependency

⁃ Platelets ≥ 100,000 / mcL

⁃ Creatinine OR Calculated creatinine clearance (institutional standard for calculation of CrCl may be used) ≤ 1.5 x upper limit of normal (ULN) OR ≥ 60 mL/min for subject with creatinine levels \> 1.5 x institutional ULN

⁃ Total bilirubin ≤ 1.5 X ULN OR Direct bilirubin ≤ ULN for subjects with total bilirubin levels \> 1.5 ULN OR total bilirubin ≤ 2 x ULN if liver metastases are present (patients with Gilbert's syndrome are allowed)

⁃ Aspartate aminotransferase (AST) and Alanine aminotransferase (ALT) ≤ 2.5 X ULN OR ≤ 5 x ULN for subjects with liver metastases

⁃ Albumin \> 3.0 g/dL

• Females of childbearing potential must have a negative pregnancy test within 72 hours prior to registration. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required. NOTE: Females are considered of child bearing potential unless they are surgically sterile (have undergone a hysterectomy, bilateral tubal ligation, or bilateral oophorectomy) or they are naturally postmenopausal for at least 12 consecutive months

• Females of childbearing potential and males must be willing to abstain from heterosexual intercourse or to use 2 forms of effective methods of contraception from the time of informed consent (females)/prior to C1D1 (males) until 120 days after treatment discontinuation.

• Willingness to return to the enrolling institution for follow up