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

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

  • Clin Cancer Res. 2022 Jan 1;28(1):71-83. doi: 10.1158/1078-0432.CCR-21-0845.
Adi Diab 1,  Omid Hamid 2,  John A Thompson 3,  Willeke Ros 4,  Ferry A L M Eskens 5,  Toshihiko Doi 6,  Siwen Hu-Lieskovan 7,  Samuel J Klempner 8,  Bishu Ganguly 9,  Catherine Fleener 9,  Xiao Wang 9,  Tenshang Joh 9,  Ken Liao 9,  Shahram Salek-Ardakani 9,  Carrie Turich Taylor 9,  Jeffrey Chou 9,  Anthony B El-Khoueiry 10
Affiliations

Affiliations

  • 1 Department of Melanoma Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas. [email protected].
  • 2 Immuno-Oncology and Cutaneous Malignancies, The Angeles Clinic and Research Institute, a Cedars-Sinai Affiliate, Los Angeles, California.
  • 3 Division of Medical Oncology, University of Washington School of Medicine/Seattle Cancer Care Alliance, Seattle, Washington.
  • 4 Department of Pharmacology, Netherlands Cancer Institute, Amsterdam, the Netherlands.
  • 5 Department of Medical Oncology, Erasmus MC Cancer Institute, Rotterdam, the Netherlands.
  • 6 Department of Gastrointestinal Oncology, National Cancer Center Hospital East, Kashiwa, Chiba, Japan.
  • 7 Division of Hematology-Oncology, Department of Medicine, University of California, Los Angeles (UCLA), Los Angeles, California.
  • 8 Department of Medicine, Massachusetts General Hospital Cancer Center, Boston, Massachusetts.
  • 9 Pfizer, New York, New York.
  • 10 Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, California.
PMID: 34615725 DOI: 10.1158/1078-0432.CCR-21-0845
Abstract

Purpose: Stimulation of effector T cells is an appealing immunotherapeutic approach in oncology. OX40 (CD134) is a costimulatory receptor expressed on activated CD4+ and CD8+ T cells. Induction of OX40 following antigen recognition results in enhanced T-cell activation, proliferation, and survival, and OX40 targeting shows therapeutic efficacy in preclinical studies. We report the monotherapy dose-escalation portion of a multicenter, phase I trial (NCT02315066) of ivuxolimab (PF-04518600), a fully human immunoglobulin G2 agonistic monoclonal antibody specific for human OX40.

Patients and methods: Adult patients (N = 52) with selected locally advanced or metastatic cancers received ivuxolimab 0.01 to 10 mg/kg. Primary endpoints were safety and tolerability. Secondary/exploratory endpoints included preliminary assessment of antitumor activity and biomarker analyses.

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+ central memory T-cell proliferation and activation, and clonal expansion of CD4+ and CD8+ T cells in peripheral blood were observed at 0.1 to 3.0 mg/kg. Increased immune cell infiltrate and OX40 expression were evident in on-treatment tumor biopsies.

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.

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