Shares of MacroGenics, Inc. are falling in pre-market trading after the company announced late Friday that it has shuttered a Phase II study of its investigational drug enoblituzumab as part of a combination therapy for head and neck cancer following seven reported deaths.
The Rockville, Maryland-based company said the Phase II CP-MGA271-06 study was closed on July 7 following an internal review of safety data that included seven deaths. The clinical trial was evaluating enoblituzumab, an investigational anti-B7-H3 monoclonal antibody, in combination with either the anti-PD-1 antibodies retifanlimab or tebotelimab as a first-line treatment for patients with recurrent or metastatic squamous cell carcinoma of the head and neck (SCCHN). Merck's Keytruda and Bristol Myer Squibb's Opdivo, both checkpoint inhibitors, have been approved in the first line for this type of cancer.
Scott Koenig, president and CEO of MacroGenics, said the company's top concern is the safety of patients enrolled in its clinical studies.
"We were surprised by the emergence of these events in first-line SCCHN patients, as we had not observed any such events in an earlier, smaller study in patients with later-line SCCHN disease who were treated with enoblituzumab in combination with an anti-PD-1 antibody," Koenig said in a statement. "Similar safety events have not been reported in patients treated with MGC018, our B7-H3-targeted ADC molecule, and the decision to close the CP-MGA271-06 study does not impact our ongoing MGC018 study activities. We'd like to thank all patients, their families and caregivers who participated in the CP-MGA271-06 study."
MGC018 is being assessed in a Phase II/III study for SCCHN, as well as non-small cell lung cancer, melanoma and metastatic castration-resistant prostate cancer. Like enoblituzumab, MGC081 targets B7-H3, an antigen with broad expression across multiple solid tumor types.
In its July 8 announcement, MacroGenics said investigators determined six of the seven deaths in the Phase II study were "secondary to disease progression and/or unrelated to the study treatment." The remaining death, however, was believed to be related to the medications used in the trial.
The company noted fatal tumor-related hemorrhages and airway obstruction are known risks in patients with SCCHN. Still, MacroGenics said the incidence of fatal events seen in this study "that were potentially hemorrhagic in origin" was higher than reported for this patient population in the medical literature.
MacroGenics said it will continue to assess the study's data so far to fully understand what happened. The company noted that no hemorrhagic events or coagulopathies (bleeding disorders) were seen in the nonclinical toxicology studies of enoblituzumab. Also, MacroGenics said any fatal hemorrhages reported in earlier studies of enoblituzumab in multiple tumor types were less than 1%.
