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Margetuximab/Pembrolizumab for Previously Treated Patients With HER2-Positive Advanced Gastroesophageal Adenocarcinoma


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In a phase Ib/II trial reported in The Lancet Oncology, Daniel V.T. Catenacci, MD, and colleagues found that the combination of margetuximab and the anti–PD-1 therapy pembrolizumab showed evidence of activity in patients with previously treated HER2-positive gastroesophageal adenocarcinoma.

Daniel V.T. Catenacci, MD

Daniel V.T. Catenacci, MD

As stated by the investigators, margetuximab is a novel Fc-engineered anti-HER2 monoclonal antibody that is designed to more effectively potentiate innate immunity compared with trastuzumab.

Study Details

The study enrolled 95 patients with unresectable locally advanced or metastatic HER2-positive, PD-L1­–unselected disease. Patients had experienced progression after at least one previous line of therapy with trastuzumab plus chemotherapy in the locally advanced unresectable or metastatic setting. In the dose-escalation phase, 3 patients received intravenous margetuximab at 10 mg/kg plus pembrolizumab at 200 mg every 3 weeks, and 6 received the recommended phase II dose of margetuximab at 15 mg/kg plus pembrolizumab every 3 weeks. An additional 86 patients enrolled in the phase II expansion cohort received the recommended phase II dose.

Responses

Median follow-up was 19.9 months. Among 92 evaluable patients who received the phase II dose, objective response was observed in 17 (18%), with disease control achieved in 49 (53%). Median duration of response was 12.09 months. Median progression-free survival was 2.73 months and median overall survival was 12.48 months. Objective response was observed in 11 (33%) of 33 patients with PD-L1–positive tumors.

KEY POINTS

  • Objective response was observed in 18% of patients.
  • Median duration of response was 12 months.

Adverse Events

No dose-limiting toxicities were observed in the dose-escalation phase. Among all 95 patients, treatment-related grade 3 or 4 adverse events occurred in 20%, with the most common being anemia (4%) and infusion-related reactions (3%). Serious treatment-related adverse events were reported in 9% of patients, and included autoimmune hepatitis in two and pneumonitis, hyponatremia, diabetic ketoacidosis, hypotension, infusion-related reaction, and dehydration in one patient each. Adverse events led to death in three patients, due to esophageal hemorrhage, peritonitis, and acute respiratory failure; none of the deaths was considered treatment-related.

The investigators concluded, “These findings serve as proof of concept of synergistic antitumour activity with the combination of an Fc-optimised anti-HER2 agent (margetuximab) along with anti–PD-1 checkpoint blockade (pembrolizumab).”

Dr. Catenacci, of the University of Chicago Medical Center, is the corresponding author for The Lancet Oncology article.

Disclosure: The study was funded by MacroGenics. For full disclosures of the study authors, visit thelancet.com.

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.
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