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.

Clinical Cancer Research : an Official Journal of the American Association for Cancer Research
Ajay K GopalNancy L Bartlett

Abstract

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). 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). 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...Continue Reading

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Citations

Jun 18, 2020·Cancers·Gaël Roué, Brigitte Sola
Dec 3, 2020·Vaccines·Robert PytlikPavel Klener
Jan 13, 2021·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Stephen M Ansell
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Jan 13, 2021·Cancers·Marc ArmengolGaël Roué
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Oct 9, 2021·Journal of Internal Medicine·Luca MazzarellaMats Jerkeman

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