ArticleCPT: pharmacometrics & systems pharmacology2023
Copanlisib population pharmacokinetics from phase I-III studies and exposure-response relationships in combination with rituximab.
Article in CPT: pharmacometrics & systems pharmacology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
4 citing papers in PubMed.
- CHRONOS-4: phase 3 study of copanlisib plus rituximab-based immunochemotherapy in relapsed indolent B-cell lymphoma.Blood advances · 2024Trial
- Safety and Efficacy of Copanlisib in Combination with Nivolumab: A Phase Ib Study in Patients with Advanced Solid Tumors.Cancer research communications · 2025Article
- Copanlisib population pharmacokinetics from phase I-III studies and exposure-response relationships in combination with rituximab.CPT: pharmacometrics & systems pharmacology · 2023Article
- Role of pharmacometrics and systems pharmacology in facilitating efficient dose optimization in oncology.CPT: pharmacometrics & systems pharmacology · 2023Article
Corrections and comments
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Authors and funding
9 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Copanlisib dose selection was established under the maximum tolerated dose paradigm, and no dedicated dose-finding studies have investigated copanlisib dose selection when used in combination with rituximab. In CHRONOS-3, copanlisib plus rituximab demonstrated significantly improved progression-free survival versus placebo plus rituximab in patients with relapsed indolent non-Hodgkin lymphoma (iNHL). We conducted a comprehensive investigation of copanlisib population pharmacokinetics (PopPK) from a pooled analysis of 712 patients across nine copanlisib phase I-III studies and exposure-response (ER) relationships for efficacy and safety from the 1-year follow-up of CHRONOS-3. PopPK analyses examined the impact of demographic, laboratory, and comedication covariates on copanlisib between-patient PK variability. Individual static and time-varying exposure estimates were derived to investigate exposure-efficacy and exposure-safety relationships. Multivariate Cox proportional hazards and logistic regression analyses examined ER relationships with consideration of predefined potentially prognostic demographic-, laboratory-, and/or disease-related baseline covariates. Copanlisib PK were best described by a three-compartment model with first-order elimination. Individual identified covariates had modest effects on copanlisib PK and were generally in line with known copanlisib disposition properties. In CHRONOS-3, ER analyses showed a significant relationship between time-varying exposure estimates and progression-free survival, and no significant exposure-safety relationships. Thus, lower copanlisib doses may result in reduced efficacy but not necessarily improved safety or tolerability. These outcomes substantiate the current intermittent dosing regimen of copanlisib 60 mg on days 1, 8, and 15 of a 28-day cycle and support the observed clinical results of copanlisib in combination with rituximab in the iNHL population.
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