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MAHOGANY: Margetuximab and Retifanlimab Combination Is Well-Tolerated in Patients with HER2-Positive, PD-L1–Positive, Metastatic Gastroesophageal Adenocarcinoma

2021 Year in Review - Gastrointestinal Cancer

MAHOGANY Cohort A clinical trial results reveal margetuximab and retifanlimab combination treatment led to tumor response with an acceptable safety profile.

Gastroesophageal adenocarcinoma (GEA) is commonly diagnosed at an advanced stage, giving patients a poor prognosis with a 5-year survival rate of approximately 15% to 25%.1 HER2 is overexpressed in approximately 10% to 30% of GEA cases, which may indicate an aggressive growth pattern although this is not entirely clear.1 Standard treatment for patients with metastatic GEA is multimodal and includes chemotherapy, radiation, targeted drug therapy, or immunotherapy.2,3 In HER2-positive metastatic GEA, trastuzumab, a monoclonal antibody, along with chemotherapy, is the first-line standard of care. Margetuximab is also an anti-HER2 monoclonal antibody that confers antitumor activity. It is an investigational drug in GEA. The MAHOGANY study is a 2-cohort study investigating the use of margetuximab and retifanlimab, an investigational humanized immunoglobulin G4 monoclonal antibody that binds to PD-1 to block interaction with PD-L1/2 in patients with unresectable metastatic/locally advanced GEA.

At the European Society for Medical Oncology Congress 2021, Catenacci and colleagues presented results from Cohort A of the MAHOGANY trial. Cohort A was designed to determine the safety and efficacy of margetuximab and retifanlimab in patients with HER2/3-positive, PD-L1–positive (combined positive score ≥1), and non–microsatellite instability-high patients. Cohort A’s primary end point was overall response rate.

There were 43 patients enrolled in the study with a median exposure of 4.2 months and a median follow-up duration of 4.6 months. First tumor reassessment was reached by 37 patients. Stable disease was found in 7 patients and 1 patient had a confirmed complete response. Confirmed partial responses were found in 11 patients, 1 patient had an unconfirmed complete response, and 11 patients had an unconfirmed partial response. Progressive disease was found in 6 patients; 5 of these 6 patients had progressive disease at first scan, and 1 had clinical progressive disease. Tumor shrinkage analysis determined 30 of 35 patients had ≥1 post-baseline target lesion measurements.

Margetuximab and retifanlimab were generally well-tolerated by the trial participants. Treatment-related adverse event (AE) evaluation found 8 AEs related to infusion, 6 patients reported diarrhea, and 6 patients experienced fatigue. One patient discontinued treatment because of renal dysfunction and 1 patient experienced immune-related renal dysfunction. Hypothyroidism developed in 4 patients. There were no grade ≥3 infusion-related reactions.

Margetuximab and retifanlimab in combination led to tumor response and was well-tolerated in patients with HER2-positive, PD-L1–positive, metastatic GEA in the MAHOGANY clinical trial.

Source: Catenacci DV, Park H, Shim BY, et al. Margetuximab (M) with retifanlimab (R) in HER2+, PD-L1+ 1st-line unresectable/metastatic gastroesophageal adenocarcinoma (GEA): MAHOGANY cohort A. Ann Oncol. 2021;32(suppl_5):S1040-S1075.

References

  1. Abdelhakeem A, Wang X, Rogers J, et al. Outcomes of advanced gastroesophageal cancer patients with equivocal HER2 expression with or without ERBB2 gene amplification. Oncology. 2020;98:884-888.
  2. Oo AM, Ahmed S. Overview of gastroesophageal junction cancers. Mini-invasive Surg. 2019;3:13.
  3. American Cancer Society. Treating esophageal cancer by stage. Updated May 21, 2021. www.cancer.org/cancer/esophagus-cancer/treating/by-stage.html. Accessed October 12, 2021.