Final Results of Urelumab, an Anti-CD137 Agonist Monoclonal Antibody, in Combination With Cetuximab or Nivolumab in Patients With Advanced Solid Tumors

Authors

Nikhil I Khushalani
Patrick A Ott
Robert L Ferris
Tina Cascone
Dirk Schadendorf
Dung T Le
Manish R Sharma
Fabrice Barlesi
William Sharfman
Jason J Luke
Ignacio Melero
Deanne Lathers
Jaclyn Neely
Satyendra Suryawanshi
Abanti Sanyal
James L Holloway
Rasika Suryawanshi
Scott Ely
Neil H Segal

Publication Date

3-7-2024

Journal

The Journal for ImmunoTherapy of Cancer

Abstract

BACKGROUND: Resistance to immune checkpoint inhibitors and targeted treatments for cancer is common; thus, novel immunotherapy agents are needed. Urelumab is a monoclonal antibody agonist that binds to CD137 receptors expressed on T cells. Here, we report two studies that evaluated urelumab in combination with cetuximab or nivolumab in patients with select, advanced solid tumors.

METHODS: CA186-018: Patients with metastatic colorectal cancer or metastatic squamous cell carcinoma of the head and neck (SCCHN) were treated in a dose-evaluation phase with urelumab 0.1 mg/kg (urelumab-0.1) every 3 weeks (Q3W)+cetuximab 250 mg/m

RESULTS: CA186-018: 66 patients received study treatment. The most frequent treatment-related adverse events (TRAEs) were fatigue (75%; n=3) with urelumab-0.1+cetuximab-250 and dermatitis (45%; n=28) with urelumab-8+cetuximab-250. Three patients (5%) discontinued due to TRAE(s) (with urelumab-8+cetuximab-250). One patient with SCCHN had a partial response (objective response rate (ORR) 5%, with urelumab-8+cetuximab-250).CA186-107: 134 patients received study treatment. Fatigue was the most common TRAE (32%; n=2 with urelumab-3+nivolumab-3; n=1 with urelumab-8+nivolumab-3; n=40 with urelumab-8+nivolumab-240). Nine patients (7%) discontinued due to TRAE(s) (n=1 with urelumab-3+nivolumab-3; n=8 with urelumab-8+nivolumab-240). Patients with melanoma naive to anti-PD-1 therapy exhibited the highest ORR (49%; n=21 with urelumab-8+nivolumab-240). Intratumoral gene expression in immune-related pathways (CD3, CD8, CXCL9, GZMB) increased on treatment with urelumab+nivolumab.

CONCLUSIONS: Although the addition of urelumab at these doses was tolerable, preliminary response rates did not indicate an evident additive benefit. Nevertheless, the positive pharmacodynamics effects observed with urelumab and the high response rate in treatment-naive patients with melanoma warrant further investigation of other anti-CD137 agonist agents for treatment of cancer.

Keywords

Humans, Nivolumab, Cetuximab, Melanoma, Carcinoma, Non-Small-Cell Lung, Lung Neoplasms, Antibodies, Monoclonal, Squamous Cell Carcinoma of Head and Neck, Head and Neck Neoplasms

Comments

Trial Registration: NCT02110082; and NCT02253992.

Supplementary Materials

PMID: 38458639