1. Patients must have a history of histologically or cytologically confirmed AGC and must

have experienced documented objective radiographic or pathologic disease progression

during or after first-line therapy for their disease.

2. HER2-positive tumor (primary tumor or metastatic lesion), defined as either IHC 3+ alone

or IHC 2+ in combination with ISH+, prospectively confirmed by a Sponsor-designated

central laboratory prior to enrollment. ISH positivity is defined as a ratio of ≥2.0 for the

number of HER2 gene copies to the number of signals for CEP17.

a) Archival tumor samples obtained from primary or metastatic sites (original diagnostic

specimens) are preferred.

b) The block or slides should include a representative part of the tumor with an invasive

tumor area for central confirmation of HER2 status.

i. If formalin-fixed paraffin-embedded (FFPE) tissue blocks (or partial block)

are unavailable due to country or site regulations, a minimum of 8 freshly cut

unstained slides MUST be available for central review of HER2 status and up to

5 additional slides for mandatory biomarker research, if sufficient tissue is available.

3. Patients must have received at least one prior chemotherapy regimen for AGC; prior

therapy does not need to have included HER2-directed therapy.

4. Adjuvant or neoadjuvant chemotherapy or chemoradiation therapy for AGC is allowed.

Patients whose AGC progresses or recurs in less than 6 months after completion of their

adjuvant or neoadjuvant therapy are allowed to participate. In these cases, the adjuvant or

neoadjuvant therapy will count as one prior therapy.

General inclusion criteria

Age ≥ 18 years

7. ECOG performance status of 0 or 1.

8. Life expectancy of at least 12 weeks from the first dose of study treatment

9. Adequate organ function as determined by the following laboratory results, within 14 days

prior to randomization

a) Neutrophils ≥ 1500 cells/mm3

b) Platelets ≥ 100,000 cells/mm3

c) Hemoglobin ≥ 9.0 g/dL; patients may receive red blood cell transfusions to attain this

concentration

d) Serum creatinine ≤ 1.5 times the upper limit of normal (ULN)

e) INR < 1.5 and aPTT < 1.5 × ULN (unless on therapeutic anticoagulation medication)

f) Serum AST or ALT < 2.5 × ULN; if bone metastases are present and alkaline

phosphatase > 2.5 × ULN, AST and ALT must be < 1.5 × ULN

g) Serum alkaline phosphatase may be > 2.5 × ULN only if bone metastases are present

and both AST and ALT < 1.5 × ULN

h) Serum total bilirubin < 1.5 × ULN. Patients with increased total bilirubin > 1.5 × ULN

due to Gilbert’s syndrome are allowed if the direct (conjugated) bilirubin level is within

normal limits.

10. Willingness and ability to comply with scheduled visits, treatment plans, laboratory tests,

and other study procedures, specifically including protocol specified pharmacokinetic

(PK) sampling.

Pregnancy test if the patient is of childbearing potential (including premenopausal women

who have had a tubal ligation)

a) A serum ß-human chorionic gonadotropin (ß-HCG) pregnancy test must be performed

at screening for women of childbearing potential, and for all women not meeting the

definition of postmenopausal (≥ 12 months of amenorrhea) and who have not

undergone surgical sterilization with a hysterectomy and/or bilateral oophorectomy.

Patients with a negative serum pregnancy test but a positive urine pregnancy test are

not eligible.

b) Subsequent tests will be urine pregnancy tests. Any positive urine pregnancy test

result must be confirmed by a serum ß-HCG test.

c) For all other women, documentation must be present in medical history confirming that

the patient is not of childbearing potential.

12. Women of childbearing potential and men with partners of childbearing potential must be

willing to use a highly effective, non-hormonal form of contraception or two effective forms

of contraception by the patient and/or partner and continue its use for the duration of study

treatment and for 6 months after the last dose of study treatment.