A Phase I, Open-Label, Dose-Escalation Study of the OX40 Agonist Ivuxolimab in Patients with Locally Advanced or Metastatic Cancers

Authors

Adi Diab
Omid Hamid
John A Thompson
Willeke Ros
Ferry A L M Eskens
Toshihiko Doi
Siwen Hu-Lieskovan
Samuel J Klempner
Bishu Ganguly
Catherine Fleener
Xiao Wang
Tenshang Joh
Ken Liao
Shahram Salek-Ardakani
Carrie Turich Taylor
Jeffrey Chou
Anthony B El-Khoueiry

Publication Date

1-1-2022

Journal

Clinical Cancer Research

Abstract

PURPOSE: Stimulation of effector T cells is an appealing immunotherapeutic approach in oncology. OX40 (CD134) is a costimulatory receptor expressed on activated CD4

PATIENTS AND METHODS: Adult patients (

RESULTS: The most common all-causality adverse events were fatigue (46.2%), nausea (28.8%), and decreased appetite (25.0%). Of 31 treatment-related adverse events, 30 (96.8%) were grade ≤2. No dose-limiting toxicities occurred. Ivuxolimab exposure increased in a dose-proportionate manner from 0.3 to 10 mg/kg. Full peripheral blood target engagement occurred at ≥0.3 mg/kg. Three (5.8%) patients achieved a partial response, and disease control was achieved in 56% of patients. Increased CD4

CONCLUSIONS: Ivuxolimab was generally well tolerated with on-target immune activation at clinically relevant doses, showed preliminary antitumor activity, and may serve as a partner for combination studies.

Keywords

Antibodies, Monoclonal, Antineoplastic Agents, CD8-Positive T-Lymphocytes, Humans, Nausea, Neoplasms

DOI

10.1158/1078-0432.CCR-21-0845

PMID

34615725

PMCID

PMC9401502

PubMedCentral® Posted Date

10-6-2021

PubMedCentral® Full Text Version

Post-print

Published Open-Access

yes