First-in-human phase I/II, open-label study of the anti-OX40 agonist INCAGN01949 in patients with advanced solid tumors

• DOI: 10.1136/jitc-2021-004235
• Publication Date: 2022-10-31T15:06:42Z
• Authors: Elizabeth J Davis; Juan Martin-Liberal; Rebecca Kristeleit; Daniel C Cho; Sarah P Blagden; Dominik Berthold; Dana B Cardin; Maria Vieito; Rowan E Miller; Prashanth Hari Dass; Angela Orcurto; Kristen Spencer; John E Janik; Jason Clark; Thomas Condamine; Jennifer Pulini; Xuejun Chen; Janice M Mehnert
• Keywords: Tolerability; Pharmacodynamics

Background OX40 is a costimulatory receptor upregulated on antigen-activated T cells and constitutively expressed regulatory (Tregs). INCAGN01949, fully human immunoglobulin G1κ anti-OX40 agonist monoclonal antibody, was designed to promote tumor-specific immunity by effector T-cell activation Fcγ receptor-mediated Treg depletion. This first-in-human study conducted determine the safety, tolerability, preliminary efficacy of INCAGN01949. Methods Phase I/II, open-label, non-randomized, dose-escalation dose-expansion in patients with advanced or metastatic solid tumors. Patients received INCAGN01949 monotherapy (7–1400 mg) 14-day cycles while deriving benefit. Safety measures, clinical activity, pharmacokinetics, pharmacodynamic effects were assessed summarized descriptive statistics. Results Eighty-seven enrolled; most common tumor types colorectal (17.2%), ovarian (8.0%), non-small cell lung (6.9%) cancers. median three (range 1–9) prior therapies, including immunotherapy 24 (27.6%). Maximum tolerated dose not reached; one patient (1.1%) receiving 350 mg reported dose-limiting toxicity grade 3 colitis. Treatment-related adverse events 45 (51.7%), fatigue (16 (18.4%)), rash (6 (6.9%)), diarrhea (6.9%)) being frequent. One gallbladder cancer achieved partial response (duration 6.3 months), 23 (26.4%) stable disease (lasting >6 months patient). occupancy maintained over 90% among all doses ≥200 mg, no treatment-emergent antidrug antibodies detected across levels. Pharmacodynamic results demonstrated that treatment did enhance proliferation peripheral blood reduce circulating Tregs, analyses biopsies demonstrate any consistent increase infiltration function, decrease infiltrating Tregs. Conclusion No safety concerns observed However, responses post-therapy limited. Studies evaluating combination other therapies are needed further evaluate potential agonism as therapeutic approach Trial registration number NCT02923349 .