Phase 1/2 study of INCAGN01876, an anti-glucocorticoid-induced tumor necrosis factor receptor agonist monoclonal antibody, plus immunotherapy for advanced cancers
The Oncologist, 2026
Hamid O., Forget F., Johnson M., George T., Bourayou N., Ioannidis S., Zhou F., Yang H., Dong Z., Gutierrez M.
| Disease area | Application area | Sample type | Products |
|---|---|---|---|
Oncology Immunotherapy | Pathophysiology | Plasma |  Olink Target 96 |
Abstract
Background
Modulating tumor-mediated immunosuppression with immunotherapies is an effective therapeutic approach for solid tumors. INCAGN01876 is a humanized IgG1 anti-glucocorticoid-induced tumor necrosis factor receptor (GITR) monoclonal antibody. This phase 1/2 trial evaluated INCAGN01876 plus nivolumab and/or ipilimumab for advanced malignancies.
Methods
In phase 1 (dose escalation), patients received various INCAGN01876 plus nivolumab and/or ipilimumab regimens. In phase 2 (dose expansion), patients with select tumors received INCAGN01876 plus ipilimumab (treatment group [TG] C2) or INCAGN01876 plus nivolumab (TGF). Primary endpoints: safety (phase 1), objective response rate (ORR; phase 2).
Results
Overall, 145 patients were enrolled: 51 and 94 in phases 1 and 2, respectively (TGC2, n = 8; TGF, n = 86 [squamous cell carcinoma of the head and neck, SCCHN, n = 46]). Four patients had dose-limiting toxicities; maximum tolerated dose was not reached; INCAGN01876 300 mg Q2W was selected as the recommended phase 2 dose based on safety with nivolumab and/or ipilimumab and safety and pharmacokinetic/pharmacodynamic monotherapy data from the INCAGN 1876-101 phase 1 study. INCAGN01876-related treatment-emergent adverse events (TEAEs) occurred in 62.8% of patients (most commonly pruritus, 16.6%); grade ≥3, 13.8%. Immune-related TEAEs occurred in 31.0% of patients (most frequently pruritus, 11.7%) most were (75.6%) grade 1/2 events. Antitumor activity was observed in TGF cohorts with SCCHN or cervical cancer (ORR 23.9% and 16.7%, respectively).
Conclusion
INCAGN01876 plus nivolumab and/or ipilimumab was generally well tolerated, with a safety profile consistent with previous reports. This observation, along with encouraging antitumor activity in SCCHN and cervical cancer, supports development of INCAGN01876 combined with immune checkpoint inhibitors.