A Study of TRK-950 When Used in Combination with Ramucirumab and Paclitaxel in Patients with Gastric Cancer

Inclusion Criteria:

• Histologically or cytologically confirmed metastatic, or locally advanced andunresectable gastric or GEJ adenocarcinoma.

• The patient is eligible to receive Ramucirumab + Paclitaxel.

• Documented objective radiographic or clinical disease progression (e.g., any new orworsening malignant effusion documented by ultrasound examination) which may beconfirmed by pathologic criteria (histology and/or cytology) if appropriate, duringor after treatment. The prior treatment must meet one of the following criteria withthe following treatment history:

1. First treatment for metastatic disease or locally advanced disease withoutexperiencing adjuvant / neo-adjuvant treatment, which progressed duringtreatment or within 4 months after the last dose of treatment

2. Adjuvant / neo-adjuvant treatment which progressed more than 6 months after thelast dose of treatment and first treatment for metastatic disease or locallyadvanced disease, which progressed during the treatment or within 4 monthsafter the last dose of treatment

3. Adjuvant / neo-adjuvant treatment which progressed during treatment or within 6months after the last dose of treatment

4. Adjuvant / neo-adjuvant treatment which progressed during treatment or within 6months after the last dose of treatment and first treatment for metastaticdisease or locally advanced disease, which progressed during treatment orwithin 4 months after the last dose of treatment

• Presence of primary or metastatic disease, measurable per RECIST v1.1 on CT scan.

• Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1.

• Life expectancy of at least 3 months.

• Age ≥ 18 years in the US and Japan, and ≥ 19 years of age in Korea.

• Signed, written IRB-approved informed consent.

• Adequate organ function from specimens collected within 14 days prior to Day 1.

• For men and women of child-producing potential, the use of effective contraceptivemethods during the study and for 6 months after the last dose of TRK-950.

• All patients must sign a pre-screening consent to assess tumor tissue to determineeligibility. Tumor tissue must be evaluable for CAPRIN-1 staining at a CLIAcertified laboratory and meet or exceed the cutoff value (30% at ≥ 2+ staining) asdefined in the expression level requirements.

Exclusion Criteria:

• Prior history of treatment with ramucirumab or paclitaxel.

• HER2 positive gastric or GEJ adenocarcinoma.

• Major surgery within 28 days prior to randomization.

• Baseline corrected QT (QTc) interval of > 470 msec for females and > 450 msec formales calculated using Fridericia's formula.

• New York Heart Association (NYHA) Class II - IV symptomatic congestive heartfailure, or symptomatic or poorly controlled cardiac arrhythmia.

• The patient has experienced any arterial thrombotic event, including myocardialinfarction, unstable angina, cerebrovascular accident, or transient ischemic attack,within 3 months prior to randomization.

• The patient has a history of (non-infectious) pneumonitis that required steroids orhas current pneumonitis.

• Clinically symptomatic venous thromboembolism or current treatment withanti-coagulants. (Patients receiving prophylactic and low-dose anticoagulationtherapy are eligible provided that the coagulation parameter defined in theInclusion Criterion 9 is met.)

• Uncontrolled arterial hypertension ≥ 150 mmHg (systolic) or ≥ 90 mmHg (diastolic)despite standard medical management.

• Active, uncontrolled bacterial, viral, or fungal infections, requiring systemictherapy.

• Pregnant or nursing women.

• Treatment with radiation therapy within 2 weeks, or treatment with chemotherapy,immunotherapy, targeted therapy, or investigational therapy within 4 weeks prior torandomization (within 2 weeks for Oral FU (S1 and capecitabine)).

• The patient has significant bleeding disorders, vasculitis, or had a significantbleeding episode from the gastrointestinal tract within 3 months prior torandomization.

• Clinically significant ascites, paracentesis in the last 3 months, or undergoesregular paracentesis procedures.

• History of gastrointestinal perforation and/or fistulae within 6 months prior torandomization.

• The patient has a serious or non-healing wound, peptic ulcer, or bone fracturewithin 28 days prior to randomization.

• The patient has a bowel obstruction, history or presence of inflammatory enteropathyor extensive intestinal resection (e.g., hemicolectomy or extensive small intestineresection with chronic diarrhea), Crohn's disease, ulcerative colitis, or chronicdiarrhea.

• Known active infection with HIV, hepatitis B or hepatitis C. Patients with a historyof hepatitis B or C are allowed if HBV DNA or Hep C RNA are undetectable.

• The patient is currently enrolled in a clinical trial involving an investigationalproduct or non-approved use of a drug, or concurrently enrolled in any other type ofmedical research judged not to be scientifically or medically compatible with thisstudy. Patients who have recently discontinued dosing of study drug are eligible toparticipate as long as the final dose of study drug was ≥ 28 days from randomizationfor participation in this study. Patients participating in surveys or observationalstudies are eligible to participate in this study.