Combination Margetuximab and Pembrolizumab for Advanced, Metastatic HER2(+) Gastric or Gastroesophageal Junction Cancer

Detailed Description: Both margetuximab and pembrolizumab are monoclonal antibodies used in
combination to treat HER2+ gastric and gastroesophageal junction cancer. This study has two
parts: Dose Escalation and Dose Expansion. The Dose Escalation phase of the study will
evaluate safety of escalating doses of the combination treatment. The Dose Expansion phase
will evaluate safety and activity of the combination once the final dose and schedule are
defined.

Inclusion Criteria:

1. Signed written informed consent.

2. Age ≥ 18 years old.

3. Unresectable locally advanced or metastatic histologically proven HER2+
gastroesophageal junction (GEJ) or gastric adenocarcinoma.

4. HER2+ as 3+ by IHC or in-situ hybridation (ISH) amplified.

5. Have received prior treatment with trastuzumab.

6. Have received treatment with at least one or more lines of cytotoxic chemotherapy in
the metastatic setting.

7. Resolution of chemotherapy, immunotherapy or radiation-related toxicities.

8. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.

9. Life expectancy ≥ 12 weeks.

10. Measurable disease as per RECIST 1.1 criteria.

11. Archival or newly obtained tissue sample of a tumor lesion.

12. Adequate organ function as determined by following laboratory parameters:

1. Heme: Plt Ct ≥ 100 x 103/µL, ANC ≥ 1.5 x 103/µL, and Hemoglobin ≥ 9 g/dL

2. Chemistry: ALT/AST ≤ 3.0 x ULN, TBili ≤1.5 x ULN, and Cr < 2 mg/dL

13. Female patients of childbearing potential must have a negative pregnancy test and
agree to use two forms of acceptable contraceptive measures from the time of consent
through 120 days after discontinuation of study drug administration.

14. Male patients with partners of childbearing potential must use barrier contraception.

Exclusion Criteria:

1. Patients with symptomatic central nervous system (CNS) metastases.

2. Patients with any history of known or suspected autoimmune disease with the specific
exceptions of vitiligo, atopic dermatitis, or psoriasis not requiring systemic
treatment.

3. History of prior allogeneic bone marrow, stem-cell or solid organ transplantation.

4. Treatment with any systemic anti-neoplastic therapy, or investigational therapy within
the 3 weeks prior to the initiation of study drug.

5. Treatment with radiation therapy within 3 weeks prior to the initiation of study drug
administration.

6. Treatment with corticosteroids (≥10 mg per day prednisone or equivalent) or other
immune suppressive drugs within the 14 days prior to the initiation of study drug
administration.

7. History of clinically-significant cardiovascular disease.

8. Clinically-significant pulmonary compromise, including a requirement for supplemental
oxygen use to maintain adequate oxygenation.

9. Presence of active pneumonitis

10. Clinically-significant gastrointestinal disorders, such as perforation,
gastrointestinal bleeding, or diverticulitis.

11. Evidence of active viral, bacterial, or systemic fungal infection.

12. Known positive testing for human immunodeficiency virus (HIV)or history of acquired
immune deficiency syndrome (AIDS).

13. Known history of or positive test for hepatitis B or hepatitis C infection.

14. Second primary invasive malignancy that has not been in remission for greater than 2
years.

15. Known hypersensitivity to recombinant proteins, polysorbate 80 or any excipient
contained in the drug or vehicle formulation for margetuximab or pembrolizumab.

16. Female patient who is breastfeeding.