A Phase 1b/2, Open Label, Dose Escalation Study of Margetuximab in Combination With Pembrolizumab in Patients With Relapsed/Refractory Advanced HER2+ Gastroesophageal Junction or Gastric Cancer
This goal of this clinical research study is to learn about the safety and activity of margetuximab and pembrolizumab combination treatment in patients with HER2+ gastric and gastroesophageal junction cancer.
Cancer (Oncology) - Esophageal,
Cancer (Oncology) - Stomach,
Cancer (Oncology) - Gastroesophageal Junction,
Phillip Gold, MD
Swedish Cancer Institute
|Ages Eligible for Study:
||18 Years and older
|Genders Eligible for Study:
|Accepts Healthy Volunteers:
- Signed written informed consent.
- Age ≥ 18 years old.
- Unresectable locally advanced or metastatic histologically proven HER2+ gastroesophageal junction (GEJ) or gastric adenocarcinoma.
- HER2+ as 3+ by IHC or in-situ hybridation (ISH) amplified.
- Have received prior treatment with trastuzumab.
- Have received treatment with at least one or more lines of cytotoxic chemotherapy in the metastatic setting.
- Resolution of chemotherapy, immunotherapy or radiation-related toxicities.
- Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
- Life expectancy ≥ 12 weeks.
- Measurable disease as per RECIST 1.1 criteria.
- Archival or newly obtained tissue sample of a tumor lesion.
Adequate organ function as determined by following laboratory parameters:
- Heme: Plt Ct ≥ 100 x 103/µL, ANC ≥ 1.5 x 103/µL, and Hemoglobin ≥ 9 g/dL
- Chemistry: ALT/AST ≤ 3.0 x ULN, TBili ≤1.5 x ULN, and Cr < 2 mg/dL
- 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.
- Male patients with partners of childbearing potential must use barrier contraception.
- Patients with symptomatic central nervous system (CNS) metastases.
- Patients with any history of known or suspected autoimmune disease with the specific exceptions of vitiligo, atopic dermatitis, or psoriasis not requiring systemic treatment.
- History of prior allogeneic bone marrow, stem-cell or solid organ transplantation.
- Treatment with any systemic anti-neoplastic therapy, or investigational therapy within the 3 weeks prior to the initiation of study drug.
- Treatment with radiation therapy within 3 weeks prior to the initiation of study drug administration.
- 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.
- History of clinically-significant cardiovascular disease.
- Clinically-significant pulmonary compromise, including a requirement for supplemental oxygen use to maintain adequate oxygenation.
- Presence of active pneumonitis
- Clinically-significant gastrointestinal disorders, such as perforation, gastrointestinal bleeding, or diverticulitis.
- Evidence of active viral, bacterial, or systemic fungal infection.
- Known positive testing for human immunodeficiency virus (HIV)or history of acquired immune deficiency syndrome (AIDS).
- Known history of or positive test for hepatitis B or hepatitis C infection.
- Second primary invasive malignancy that has not been in remission for greater than 2 years.
- Known hypersensitivity to recombinant proteins, polysorbate 80 or any excipient contained in the drug or vehicle formulation for margetuximab or pembrolizumab.
- Female patient who is breastfeeding.