2. Academic Validation
  3. First-in-Human Study of Utomilumab, a 4-1BB/CD137 Agonist, in Combination with Rituximab in Patients with Follicular and Other CD20+ Non-Hodgkin Lymphomas

First-in-Human Study of Utomilumab, a 4-1BB/CD137 Agonist, in Combination with Rituximab in Patients with Follicular and Other CD20+ Non-Hodgkin Lymphomas

  • Clin Cancer Res. 2020 Jun 1;26(11):2524-2534. doi: 10.1158/1078-0432.CCR-19-2973.
Ajay K Gopal 1,  Ronald Levy 2,  Roch Houot 3 4 5,  Sandip P Patel 6,  Leslie Popplewell 7,  Caron Jacobson 8,  Xinmeng J Mu 9,  Shibing Deng 9,  Keith A Ching 9,  Ying Chen 9,  Craig B Davis 9,  Bo Huang 10,  Kolette D Fly 10,  Aron Thall 9,  Adrian Woolfson 11,  Nancy L Bartlett 12
Affiliations

Affiliations

  • 1 University of Washington, Fred Hutchinson Cancer Research Center, Seattle Cancer Care Alliance, Seattle, Washington. [email protected].
  • 2 Stanford Cancer Center, Stanford, California.
  • 3 1 CHU Rennes, Service Hématologie Clinique Rennes, France.
  • 4 University of Rennes, EFS, Microenvironment, Cell Differentiation, Immunology and Cancer Rennes, France.
  • 5 INSERM 0203, Unité d'Investigation Clinique, Rennes, France.
  • 6 University of California at San Diego Moores Cancer Center, San Diego, California.
  • 7 City of Hope National Medical Center, Duarte, California.
  • 8 Dana-Farber Cancer Institute, Boston, Massachusetts.
  • 9 Pfizer Oncology, San Diego, California.
  • 10 Pfizer Oncology, Groton, Connecticut.
  • 11 Pfizer Oncology, New York, New York.
  • 12 Washington University School of Medicine, Siteman Cancer Center, St Louis, Missouri.
PMID: 32144134 DOI: 10.1158/1078-0432.CCR-19-2973
Abstract

Purpose: In this phase I study (NCT01307267), we evaluated safety, pharmacokinetics, clinical activity, and pharmacodynamics of treatment with utomilumab plus rituximab in patients with relapsed/refractory follicular lymphoma (FL) and other CD20+ non-Hodgkin lymphomas (NHL).

Patients and methods: Primary objectives were to assess treatment safety and tolerability for estimating the MTD, using a modified time-to-event continual reassessment method, and selecting the recommended phase II dose (RP2D).

Results: Sixty-seven patients received utomilumab (0.03-10.0 mg/kg every 4 weeks) and rituximab (375 mg/m2 weekly) in the dose-escalation groups or utomilumab (1.2 mg/kg every 4 weeks) plus rituximab in the dose-expansion cohort. No patient experienced dose-limiting toxicity. The MTD for utomilumab in combination with rituximab was not reached and estimated to be ≥10 mg/kg every 4 weeks. The majority of the utomilumab treatment-related adverse events (AE) were grade 1 to 2; the most common AE was fatigue (16.4%). The pharmacokinetics of utomilumab in combination with rituximab was linear in the 0.03 to 10 mg/kg dose range. A low incidence (1.5%) of treatment-induced antidrug Antibodies against utomilumab was observed. The objective response rate was 21.2% (95% CI, 12.1%-33.0%) in all patients with NHL, including four complete and 10 partial responses. Analysis of paired biopsies from a relapsed/refractory FL patient with complete response showed increased T-cell infiltration and cytotoxic activity in tumors. Biomarker correlations with outcomes suggested that clinical benefit may be contingent on patient immune function.

Conclusions: Utomilumab in combination with rituximab demonstrated clinical activity and a favorable safety profile in patients with CD20+ NHLs.

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