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Cited by 43Cancer Immunotherapy and BiomarkersPharmaceutical studies and practicesMonoclonal and Polyclonal Antibodies Research

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Population pharmacokinetics, exposure-safety, and immunogenicity of atezolizumab in pediatric and young adult patients with cancer

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Shemesh, Colby S., Chanu, Pascal, Jamsen, Kris, Wada, Russ, Rossato, Gianluca, Donaldson, Francis, Garg, Amit, Winter, Helen, Ruppel, Jane, Wang, Xin, Bruno, Rene, Jin, Jin, Girish, Sandhya·2019·Journal for ImmunoTherapy of Cancer
DOI 10.1186/s40425-019-0791-xPMC PMC6868826
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Abstract

BACKGROUND: The iMATRIX-atezolizumab study was a phase I/II, multicenter, open-label study designed to assess the safety and pharmacokinetics of atezolizumab in pediatric and young adult patients. We describe the pharmacokinetics (PK), exposure-safety, and immunogenicity of atezolizumab in pediatric and young adults with metastatic solid tumors or hematologic malignancies enrolled in this study. METHODS: Patients aged < 18 years (n = 69) received a weight-adjusted dose of atezolizumab (15 mg/kg every 3 weeks [q3w]; maximum 1200 mg); those aged ≥ 18 years (n = 18) received a flat dose (1200 mg q3w). A prior two-compartment intravenous infusion input adult population-PK (popPK) model of atezolizumab was used as a basis to model pediatric data. RESULTS: A total of 431 atezolizumab serum concentrations from 87 relapse-refractory pediatric and young adult patients enrolled in the iMATRIX-atezolizumab study were used for the popPK analysis. The dataset comprised predominantly patients aged < 18 years, including two infants aged < 2 years, with a wide body weight and age range. The clearance and volume of distribution estimates of atezolizumab were 0.217 L/day and 3.01 L, respectively. Atezolizumab geometric mean trough exposures were ~ 20% lower in pediatric patients versus young adults; this was not clinically meaningful as both groups achieved the target concentration (6 μg/mL). Safety was similar between pediatric and young adult patients with no exposure-safety relationship observed. Limited responses (4/87) precluded an exposure-response assessment on outcomes. A comparable rate (13% vs 11%) of atezolizumab anti-drug antibodies was seen in pediatric and young adult patients. CONCLUSIONS: These findings demonstrate a similar exposure-safety profile of atezolizumab in pediatric and young adult patients, supportive of weight-based dosing in pediatric patients. TRIAL REGISTRATION: NCT02541604.

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  • The safe dose of atezolizumab was confirmed in pediatric and young adult patients, supportive of weight-based dosing in pediatric patients.

    “The safe dose of atezolizumab was confirmed in pediatric and young adult patients, supportive of weight-based dosing in pediatric patients [89].”

    From Advances on immunotherapy for osteosarcoma (2024) · cites this paper as [89]

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Metadata

Authors
Shemesh, C. S., Chanu, P., Jamsen, K., Wada, R., Rossato, G., Donaldson, F., Garg, A., Winter, H., Ruppel, J., Wang, X., Bruno, R., Jin, J., & Girish, S.
Affiliations
  • Genentech (US)
  • Roche (France) (FR)
  • Certara (United States) (US)
  • F. Hoffmann-La Roche AG (CH)
  • Roche (United Kingdom) (GB)
Corresponding author
Shemesh, Colby S.
ORCID
Venue
Journal for ImmunoTherapy of Cancer
Publisher
BMJ
Published
2019-11-21
Volume
7
Issue
1
Pages
314-314
ISSN
2051-1426 (ISSN-L)
DOI
10.1186/s40425-019-0791-x
PMC
PMC6868826
OpenAlex
W2990202983
Cited by
43
References
6
Citations by year
2026: 2 · 2025: 6 · 2024: 4 · 2023: 8 · 2022: 8 · 2021: 9 · 2020: 6
FWCI
2.40
Type
journal article
Language
en
Open access
Licence
Locations
  • Journal for ImmunoTherapy of Cancer (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
Funders
  • Genentech (.)
  • F. Hoffmann-La Roche (.)
Topics
  • Health Sciences › Medicine › Oncology › Cancer Immunotherapy and Biomarkers
  • Health Sciences › Medicine › Pediatrics, Perinatology and Child Health › Pharmaceutical studies and practices
  • Life Sciences › Immunology and Microbiology › Immunology › Monoclonal and Polyclonal Antibodies Research
Keywords
atezolizumab, population pharmacokinetics, childhood cancer, young adult cancer, immunogenicity, anti-drug antibodies, weight-based dosing, PD-L1 inhibitors, metastatic solid tumors, hematologic malignancies
MeSH terms
Progression-Free Survival, Adolescent, Adult, Antineoplastic Agents, Child, Child, Preschool, Female, Humans, Infant, Male, Models, Biological, Neoplasms, Treatment Outcome, Young Adult, Antibodies, Monoclonal, Humanized

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