2. Academic Validation
  3. First-In-Human Phase I Study of the OX40 Agonist MOXR0916 in Patients with Advanced Solid Tumors

First-In-Human Phase I Study of the OX40 Agonist MOXR0916 in Patients with Advanced Solid Tumors

  • Clin Cancer Res. 2022 Aug 15;28(16):3452-3463. doi: 10.1158/1078-0432.CCR-21-4020.
Tae Won Kim 1,  Howard A Burris 2,  Maria J de Miguel Luken 3,  Michael J Pishvaian 4,  Yung-Jue Bang 5,  Michael Gordon 6,  Ahmad Awada 7,  D Ross Camidge 8,  F Stephen Hodi 9,  Grant A McArthur 10,  Wilson H Miller 11,  Andres Cervantes 12,  Laura Q Chow 13,  Alexander M Lesokhin 14 15,  Annemie Rutten 16,  Mario Sznol 17,  Deepali Rishipathak 18,  Shang-Chiung Chen 18,  Eric Stefanich 18,  Tony Pourmohamad 18,  Maria Anderson 18,  Jeong Kim 18,  Mahrukh Huseni 18,  Ina Rhee 18,  Lillian L Siu 19
Affiliations

Affiliations

  • 1 Asan Medical Center, University of Ulsan, Seoul, Korea.
  • 2 Sarah Cannon Research Institute, Nashville, Tennessee.
  • 3 START-CIOCC, Hosp. HM Sanchinarro, Madrid, Spain.
  • 4 Johns Hopkins University School of Medicine, Washington, DC.
  • 5 Seoul National University College of Medicine, Seoul, Korea.
  • 6 HonorHealth Research Institute, Scottsdale, Arizona.
  • 7 Jules Bordet Institute, Brussels, Belgium.
  • 8 University of Colorado Anschutz Medical Campus, Aurora, Colorado.
  • 9 Dana-Farber Cancer Institute, Boston, Massachusetts.
  • 10 Sir Peter MacCallum Department of Oncology, University of Melbourne, Victoria, Australia.
  • 11 Jewish General Hospital and Segal Cancer Centre, McGill University, Montréal, Canada.
  • 12 Biomedical Research Institute INCLIVA, University of Valencia, Valencia Spain.
  • 13 University of Washington, Seattle, Washington.
  • 14 Memorial Sloan Kettering Cancer Center, New York, New York.
  • 15 Weill Cornell Medical College, New York, New York.
  • 16 GasthuisZusters Antwerpen Sint-Augustinus, Antwerp, Belgium.
  • 17 Yale School of Medicine, New Haven, Connecticut.
  • 18 Genentech, Inc., South San Francisco, California.
  • 19 Princess Margaret Cancer Centre, University Health Network, Toronto, Ontario, Canada.
PMID: 35699599 DOI: 10.1158/1078-0432.CCR-21-4020
Abstract

Purpose: OX40, a receptor transiently expressed by T cells upon antigen recognition, is associated with costimulation of effector T cells and impairment of regulatory T-cell function. This first-in-human study evaluated MOXR0916, a humanized effector-competent agonist IgG1 monoclonal anti-OX40 antibody.

Patients and methods: Eligible patients with locally advanced or metastatic refractory solid tumors were treated with MOXR0916 intravenously once every 3 weeks (Q3W). A 3+3 dose-escalation stage (0.2-1,200 mg; n = 34) was followed by expansion cohorts at 300 mg (n = 138) for patients with melanoma, renal cell carcinoma, non-small cell lung carcinoma, urothelial carcinoma, and triple-negative breast Cancer.

Results: MOXR0916 was well tolerated with no dose-limiting toxicities observed. An MTD was not reached. Most patients (95%) experienced at least one adverse event (AE); 56% of AEs, mostly grade 1-2, were related to MOXR0916. Most common treatment-related AEs included fatigue (17%), diarrhea (8%), myalgia (7%), nausea (6%), decreased appetite (6%), and infusion-related reaction (5%). Pharmacokinetic (PK) parameters were dose proportional between 80 and 1,200 mg and supported Q3W administration. The recommended expansion dose based on PK and OX40 receptor saturation was 300 mg Q3W. Immune activation and upregulation of PD-L1 was observed in a subset of paired tumor biopsies. One renal cell carcinoma patient experienced a confirmed partial response. Overall, 33% of patients achieved stable disease.

Conclusions: Although objective responses were rarely observed with MOXR0916 monotherapy, the favorable safety profile and evidence of tumor immune activation in a subset of patients support further investigation in combination with complementary agents such as PD-1/PD-L1 antagonists.

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