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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
- Source :
- Clinical Cancer Research, Clinical Cancer Research, American Association for Cancer Research, 2020, 26 (11), pp.2524-2534. ⟨10.1158/1078-0432.CCR-19-2973⟩, Clinical Cancer Research, 2020, 26 (11), pp.2524-2534. ⟨10.1158/1078-0432.CCR-19-2973⟩
- Publication Year :
- 2020
- Publisher :
- American Association for Cancer Research (AACR), 2020.
-
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.
- Subjects :
- 0301 basic medicine
Cancer Research
medicine.medical_specialty
[SDV]Life Sciences [q-bio]
Gastroenterology
03 medical and health sciences
0302 clinical medicine
Pharmacokinetics
immune system diseases
hemic and lymphatic diseases
Internal medicine
medicine
Adverse effect
CD20
biology
business.industry
medicine.disease
3. Good health
Lymphoma
030104 developmental biology
Oncology
Tolerability
030220 oncology & carcinogenesis
Pharmacodynamics
biology.protein
Rituximab
Refractory Follicular Lymphoma
business
medicine.drug
Subjects
Details
- ISSN :
- 15573265 and 10780432
- Volume :
- 26
- Database :
- OpenAIRE
- Journal :
- Clinical Cancer Research
- Accession number :
- edsair.doi.dedup.....e8032fdd9d848ad1659e448d964388ae