Abstract 4883
Background
HLX01, the first-ever China (CN)-manufactured rituximab (RTX) biosimilar, was approved by National Medicinal Products Administration (NMPA) for the treatment of diffuse large B-cell lymphoma (DLBCL) on 22 February 2019, and was concurrently developed as a novel drug to treat rheumatoid arthritis (RA) in CN since the indication has not been approved. The objective of this study was to develop a reliable population pharmacokinetic (PopPK) model of rituximab in patients with RA, the most appropriate patient population for PK evaluation, and validate HLX01 and CN-RTX PK data in patients with DLBCL.
Methods
A PK model for HLX01 and the EU-RTX from a randomised, double-blind phase 1/2 study (NCT03355872) in 196 RA patients (serum sample n = 4289) was developed using non-linear mixed-effect modeling (NONMEM®) with the first-order conditional estimation with interaction (FOCEI) method. PK and PK-pharmacodynamic relationship were characterised with various covariates (ie. demographics, pathphysiologic/disease conditions etc) which were examined by using forward addition (p < 0.01) / backward elimination (p < 0.001). The final model was evaluated using Bayesian bootstrap and visual predictive check (VPC). A total of 1000 simulations were tested using the observed covariates. The final model was validated using PK samples of HLX01 and CN-RTX from a randomised, double-blind phase 3 registrational study (NCT02787239) in 110 patients with CD20+ DLBCL.
Results
A two-compartment model with first-order elimination provided the best model fit. The estimated clearance (CL), central volume (Vc), peripheral compartment volume (Vp) and clearance of distribution from the central to the peripheral compartment (Q) were 27.32%, 16.56%, 21.61%, and 40.79%, respectively. The correlation between CL and Vc was 0.02239. The PopPK model of HLX01 and EU-RTX using RA patients adequately predicts the central tendency and variability of the HLX01 and CN-RTX in patients with DLBCL.
Conclusions
This PopPK model derived from RA patients can predict HLX01 and CN-RTX in patients DLBCL. HLX01 and EU-/CN-RTX had similar PK parameters and influential PK covariates. These results provided further evidence for PK similarity between HLX01 and RTXs in patients with RA or DLBCL.
Clinical trial identification
Two trials were listed in this abstract: 1. A Randomised, Double-blind, Phase 1/2 Study to Evaluate the PK, PD, Safety, and Efficacy Between HLX01 and Rituximab in Patients With Moderate to Severe Rheumatoid Arthritis and Inadequate Response to Treatment With DMARDs ClinicalTrials.gov Identifier: NCT03355872 2. Clinical Phase 3 Study to Compare the Efficacy and Safety of Rituximab Biosimilar HLX01 and Rituximab in Combination With CHOP, in Previously Untreated Subjects With CD20+ DLBCL ClinicalTrials.gov Identifier: NCT02787239.
Editorial acknowledgement
Legal entity responsible for the study
Shanghai Henlius Biotech, Inc.
Funding
Shanghai Henlius Biotech,Inc.
Disclosure
Y. Shi: Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College. Y. Dan: Full / Part-time employment: Shanghai Henlius Biotech,Inc. Y. Hong: Shareholder / Stockholder / Stock options, Full / Part-time employment: Shanghai Henlius Biotech, Inc. J. Guo: Full / Part-time employment: Shanghai Henlius Biotech, Inc. S. Zhao: Advisory / Consultancy: Certara Strategic Consulting China. X. Zeng: Research grant / Funding (institution): Peking Union Medical College Hospital. P. Hu: Research grant / Funding (institution): Peking Union Medical College Hospital. W. Jiang: Leadership role, Shareholder / Stockholder / Stock options, Full / Part-time employment, Officer / Board of Directors: I am an employee of Shanghai Henlius Biotech, Inc. S. Liu: Leadership role, Shareholder / Stockholder / Stock options, Full / Part-time employment, Officer / Board of Directors: Shanghai Henlius Biotech,Inc. X. Zhang: Leadership role, Shareholder / Stockholder / Stock options, Full / Part-time employment: Shanghai Henlius Biotech,Inc. A. Luk: Leadership role, Shareholder / Stockholder / Stock options, Full / Part-time employment, Officer / Board of Directors: Shanghai Henlius Biotech,Inc. K. Chai: Full / Part-time employment: Shanghai Henlius Biotech,Inc. E. Liu: Leadership role, Full / Part-time employment: I am an employee of Shanghai Henlius Biotech,Inc.
Resources from the same session
1269 - One-year follow-up results of eribulin for soft-tissue sarcoma including rare subtypes in a real-world observational study in Japan
Presenter: Shunji Takahashi
Session: Poster Display session 1
Resources:
Abstract
2868 - Prevalence of chemotherapy use and its impact on overall survival in patients with bone- and soft tissue sarcomas -A population-based analysis of 3746 patients
Presenter: Herbert Loong
Session: Poster Display session 1
Resources:
Abstract
3042 - Clinical course and therapeutic management of classical and endemic Kaposi’s Sarcoma (C/E KS)
Presenter: Lina Benajiba
Session: Poster Display session 1
Resources:
Abstract
3141 - The final outcomes of study on combined therapy of adult patients with localized synovial sarcoma
Presenter: Katarzyna Kozak
Session: Poster Display session 1
Resources:
Abstract
5449 - Real-world Outcomes of Patients with Locally Advanced or Metastatic Epithelioid Sarcoma
Presenter: Mrinal Gounder
Session: Poster Display session 1
Resources:
Abstract
4465 - SAKK 57/16 Nab-Paclitaxel And Gemcitabine in soft tissue sarcoma (NAPAGE): results from the phase I part of a phase I/II trial
Presenter: Antonia Digklia
Session: Poster Display session 1
Resources:
Abstract
5013 - Outcome of 98 patients with epithelioid sarcoma treated in curative intent: a retrospective study from the French Sarcoma Group (GSF-GETO)
Presenter: Maud Pedrono
Session: Poster Display session 1
Resources:
Abstract
5614 - Comparison of filgrastim and pegfilgrastim prophylaxis in sarcoma patients receiving highly myelosuppressive chemotherapy.
Presenter: Paolo Tarantino
Session: Poster Display session 1
Resources:
Abstract
1033 - Access to clinical trials for soft tissue sarcoma patients in Western and Eastern Europe
Presenter: Vasilii Ostafiichuk
Session: Poster Display session 1
Resources:
Abstract
4094 - Treatment outcomes for adult patients with localized osteosarcoma treated with chemotherapy without methotrexate
Presenter: Marília Silva
Session: Poster Display session 1
Resources:
Abstract