Phase 1 Study of INBRX-105, a TNFRSF9 (4-1BB) and PD-L1 Bispecific Antibody, in Patients With Select Solid Tumors.
Publication Title
Cancer Res Commun
Document Type
Article
Publication Date
1-27-2026
Keywords
oregon; chiles
Abstract
PURPOSE: INBRX-105, a tetravalent, PD-L1-targeted TNFRSF9 (4-1BB) agonist, demonstrated preclinical antitumor activity. This first-in-human study evaluated INBRX-105 in solid tumors.
PATIENTS AND METHODS: This open-label, 4-part, phase 1 study evaluated INBRX-105 alone or with pembrolizumab in adults with locally advanced/metastatic, unresectable solid tumors (NCT03809624). INBRX-105 was administered intravenously Q2W or Q4W in parts 1 (single-agent dose escalation; 0.001-3.0 mg/kg) and 2 (single-agent expansion) or Q3W in parts 3 (combination dose escalation; INBRX-105 0.03-1.0 mg/kg) and 4 (combination expansion). Part 2 enrolled patients with checkpoint inhibitor-relapsed/refractory (CPI-R/R) tumors. Part 4 enrolled patients with CPI-R/R or CPI-naive disease. The primary endpoint was safety and tolerability of INBRX-105. Preliminary clinical response was a secondary endpoint.
RESULTS: Of 160 patients assessed, 81 received monotherapy (median age, 65.0 years; female, 50.6%), and 79 combination therapy (median age, 64.0 years; female, 38.0%). The INBRX-105 maximum tolerated dose was 0.3 mg/kg Q3W. Head and neck squamous cell carcinoma (n=61) and non-small cell lung cancer (n=25) were the most common tumor types. The most common any-grade INBRX-105-related adverse events (AEs) were fatigue (monotherapy, 35.8%; combination, 17.7%), increased aspartate aminotransferase (25.9%; 15.2%), and nausea (19.8%; 17.7%). INBRX-105-related hepatic AEs occurred in 41 patients (monotherapy, n=25 [grade ≥3, n=11]; combination, n=16 [grade ≥3, n=6]). In all patients, the objective response rate was 8.8% (monotherapy, 3.7%; combination, 13.9% [CPI naive, 30.0%; CPI R/R, 8.6%]); disease control rate was 43.1%.
CONCLUSIONS: The low response rates and hepatic safety signals observed do not support further clinical development of INBRX-105.
Area of Special Interest
Cancer
Specialty/Research Institute
Earle A. Chiles Research Institute
Specialty/Research Institute
Oncology
DOI
10.1158/2767-9764.CRC-25-0577
