In a phase I/IIa study reported in JAMA Oncology, Lillian L. Siu, MD, FRCPC, FASCO, and colleagues found no evidence of activity of the glucocorticoid-induced tumor necrosis factor (TNF) receptor–related protein (GITR) agonist antibody BMS-986156 alone or in combination with nivolumab in patients with previously treated advanced solid tumors.
Lillian L. Siu, MD, FRCPC, FASCO
GITR is a T-cell co-stimulatory receptor identified as a therapeutic target. It has been hypothesized that agonistic GITR antibodies may exhibit synergistic activity with immune checkpoint inhibitors by activating co-stimulatory pathways in the tumor microenvironment.
Study Details
In the international study, 292 patients received either BMS-986156 alone (n = 34) or in combination with nivolumab (n = 258). BMS-986156 was given intravenously at a dose of 10, 30, 100, 240, or 800 mg every 2 weeks as monotherapy, or at 30, 100, 240, or 800 mg together with nivolumab at 240 mg every 2 weeks. Patients had to have received one or more standard treatment regimen in the advanced or metastatic setting. Prior immune checkpoint inhibitor therapy had been received by 32% of patients in the monotherapy cohort and 20% of patients in the combination cohort.
Follow-up ranged from 1.4 to 101.7 weeks. No grade ≥ 3 treatment-related adverse events were observed with BMS-986156 monotherapy. Grade or 4 treatment-related adverse events occurred in 24 patients (9.3%) receiving BMS-986156 plus nivolumab. A dose-limiting toxic effect (grade 4 elevated creatine phosphokinase) occurred in a patient receiving BMS-986156 800 mg plus nivolumab.
Effect on T Cells, Objective Responses
KEY POINTS
- No evidence of activity of BMS-986156 monotherapy was observed.
- The response rate with combination treatment did not suggest activity beyond that associated with nivolumab alone.
Peripheral T-cell and natural killer cell proliferation increased after administration of BMS-986156 with or without nivolumab. No significant modulation of intratumoral CD8-positive T cells or FoxP3-positive regulatory T cells was observed.
No objective responses were observed in patients receiving BMS-986156 alone. Response rates ranged from 0% to 11.1% across combination therapy groups. Some responses were observed in patients who had previously received immune checkpoint inhibitor therapy.
The investigators concluded, “Based on this cohort, BMS-986156 appears to have had a manageable safety profile, and BMS-986156 plus nivolumab demonstrated safety and efficacy comparable to historical data reported for nivolumab monotherapy…. [T]hus, no evidence of monotherapeutic clinical activity for GITR agonism was observed in this broad population. In addition, no clear signal has emerged to date demonstrating that GITR agonism may be an effective therapeutic strategy in a broad patient population.”
Dr. Siu, of Princess Margaret Cancer Centre, Toronto, is the corresponding author for the JAMA Oncology article.
Disclosure: This study was funded by Bristol-Myers Squibb. For full disclosures of the study authors, visit jamanetwork.com.
