Phase 2
Completed N=95
Combination Margetuximab and Pembrolizumab for Advanced, Metastatic HER2(+) Gastric or Gastroesophageal Junction Cancer
Gastric Cancer · Stomach Cancer · Esophageal Cancer
Source: ClinicalTrials.gov NCT02689284 ↗
Enrolled (actual)
95
Serious AEs
42.1%
Results posted
Aug 2022
Primary outcomePrimary: Number of Patients With Dose Limiting Toxicities — 0; 0 Participants
Summary
This main purpose of this clinical study is to learn about the safety and activity of margetuximab and pembrolizumab combination treatment in patients with HER2+ gastric and gastroesophageal junction cancer.
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Number of Patients With Dose Limiting Toxicities |
0; 0 | — |
| PRIMARY Number of Patients With Adverse Events (AEs) and Serious Adverse Events (SAEs). |
3; 86 | — |
| PRIMARY Number of Patients With a Complete Response (CR) or Partial Response (PR) to Treatment |
0; 18 | — |
| PRIMARY Number of Patients With a Complete Response (CR) or Partial Response (PR) to Treatment Using irRC Criteria |
0; 19 | — |
| PRIMARY Duration of Response |
12.1 | — |
| SECONDARY Overall Survival (OS) |
7.0; 12.7 | — |
| SECONDARY Progression Free Survival (PFS) |
1.4; 2.7 | — |
| SECONDARY Change From Baseline in Pharmacodynamic Markers in Whole Blood |
— | — |
| SECONDARY Analysis of HER2 Tumor Cell Membrane Expression in Biopsy Specimens Before and After Treatment |
— | — |
| SECONDARY Number of Patients Who Develop Treatment-emergent Anti-drug Antibodies to Margetuximab (Immunogenicity) |
1; 4 | — |
| SECONDARY Maximum Concentration of Margetuximab at Steady State |
197; 318 | — |
| SECONDARY Area Under the Concentration Time Curve at Steady State (AUC ss) |
1710; 2720 | — |
| SECONDARY Clearance |
0.381; 0.329 | — |
| SECONDARY Volume of Distribution at Steady State |
7.7; 6.37 | — |
| SECONDARY Terminal Half-life |
17.2; 16.2 | — |
Eligibility Criteria
Inclusion Criteria
- Signed written informed consent.
- Age ≥ 18 years old (or minimum age based upon local regulations)
- Unresectable locally advanced or metastatic histologically proven HER2+ gastroesophageal junction (GEJ) or gastric cancer. Gastric Cancer Expansion Phase will include only gastric cancer patients with 3+ HER2 positivity.
- HER2+ as 3+ (as defined in AJCC staging manual 8th edition) 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.
Exclusion Criteria
- 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.
- History of (non-infectious) pneumonitis that required steroids or presence of active pneumonitis
- Clinically-significant gastrointestinal disorders, such as perforation, gastrointestinal bleeding, or diverticulitis.
- Evidence of active viral, bacterial, or systemic fungal infection.
Data sourced from ClinicalTrials.gov (NCT02689284). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication. Informational only — not medical advice.