Pembrolizumab Plus T-Cell Inducer Under Study in Triple-Negative Breast Cancer
Posted: Monday, January 11, 2021
GX-17, which works through increasing the amount of T cells in tumor microenvironments and peripheral blood, combined with pembrolizumab appears to be safe and well tolerated, based on the results of the phase Ib/II KEYNOTE-899 trial. The combination treatment produced significant increases in T-cell numbers in patients with triple-negative breast cancer. Joo Sohn, MD, of Severance Hospital in Seoul, Korea, and Young Hyuk Im, MD, of the Samsung Medical Center in Seoul, Korea, published their work in the Journal for ImmunoTherapy of Cancer.
This open-label study recruited 45 patients with refractory or recurrent triple-negative breast cancer that did not respond to three prior lines of standard chemotherapy. A total of 21 patients were pretreated with cyclophosphamide and were subsequently administered between 360 μg/kg and 1,440 μg/kg of GX-17 every 12 weeks plus pembrolizumab every 3 weeks. The remaining 24 patients did not receive cyclophosphamide pretreatment but were given 720 μg/kg to 1,440 μg/kg of GX-17 every 9 or 12 weeks, plus pembrolizumab every 3 weeks.
Treatment with GX-17 produced up to a sevenfold increase in absolute neutrophil counts among all dose levels, both with and without cyclophosphamide. A total of 33 patients were evaluable for objective response rate; an objective response was achieved in 0 of 3 in the 360-μg/kg group, 1 of 9 in the 720-μg/kg group, 2 of 9 in the 960-μg/kg group, and 4 of 12 in the 1,200-μg/kg group. Of note, four of the six patients who received 1,200 μg/kg of GX-17 plus cyclophosphamide achieved stable disease, making the 1,200-μg/kg the maximum tolerated dose. Tumor assessment among the 1,440-μg/kg group is ongoing.
Grade 1 or 2 treatment-related adverse events were noted among 97.8% of patients, with 15.6% experiencing grade 3 events and 2.2% experiencing grade 4 events. Common treatment-emergent adverse events included injection-site reaction (75.6%), rash (40.0%), and pyrexia (40.0%), which were all reported to be manageable.
Disclosure: For full author disclosures, visit jitc.bmj.com.