Dataset Information

Candidate Bevacizumab Biosimilar CT-P16 versus European Union Reference Bevacizumab in Patients with Metastatic or Recurrent Non-Small Cell Lung Cancer: A Randomized Controlled Trial.

ABSTRACT:

Background

CT-P16 is a candidate bevacizumab biosimilar.

Objective

This double-blind, multicenter, parallel-group, phase III study aimed to establish equivalent efficacy between CT-P16 and European Union-approved reference bevacizumab (EU-bevacizumab) in patients with metastatic or recurrent non-squamous non-small cell lung cancer (nsNSCLC).

Patients and methods

Patients with stage IV or recurrent nsNSCLC were randomized (1:1) to receive CT-P16 or EU-bevacizumab (15 mg/kg every 3 weeks; ≤ 6 cycles) with paclitaxel (200 mg/m²) and carboplatin (area under the curve 6.0; both for 4-6 cycles), as induction therapy. Patients with controlled disease after induction therapy continued with CT-P16 or EU-bevacizumab maintenance therapy. The primary endpoint was objective response rate (ORR) during the induction period. Time-to-event analyses, pharmacokinetics, safety, and immunogenicity were also evaluated. Results obtained after 1 year of follow-up are presented.

Results

Overall, 689 patients were randomized (CT-P16, N = 342; EU-bevacizumab, N = 347). ORR was 42.40% (95% confidence interval [CI] 37.16-47.64) and 42.07% (95% CI 36.88-47.27) for CT-P16 and EU-bevacizumab, respectively. The risk difference (0.40 [95% CI - 7.02 to 7.83]) and risk ratio (1.0136 [90% CI 0.8767-1.1719]) for ORR fell within predefined equivalence margins (- 12.5 to + 12.5%, and 0.7368 to 1.3572, respectively), demonstrating equivalence between CT-P16 and EU-bevacizumab. Median response duration, time to progression, progression-free survival, and overall survival were comparable between treatment groups. Safety profiles were similar: 96.2% (CT-P16) and 93.0% (EU-bevacizumab) of patients experienced treatment-emergent adverse events. Pharmacokinetics and immunogenicity were comparable between groups.

Conclusions

Equivalent efficacy and similar pharmacokinetics, safety, and immunogenicity support bioequivalence of CT-P16 and EU-bevacizumab in patients with nsNSCLC.

Trial registration number

NCT03676192.

SUBMITTER: Verschraegen C

PROVIDER: S-EPMC9649513 | biostudies-literature | 2022 Nov

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Candidate Bevacizumab Biosimilar CT-P16 versus European Union Reference Bevacizumab in Patients with Metastatic or Recurrent Non-Small Cell Lung Cancer: A Randomized Controlled Trial.

Verschraegen Claire C Andric Zoran Z Moiseenko Fedor F Makharadze Tamta T Shevnya Sergii S Oleksiienko Alona A Yañez Ruiz Eduardo E Kim SungHyun S Ahn KeumYoung K Park TaeHong T Park Sijin S Ju Hana H Ohe Yuichiro Y

BioDrugs : clinical immunotherapeutics, biopharmaceuticals and gene therapy 20220928 6

<h4>Background</h4>CT-P16 is a candidate bevacizumab biosimilar.<h4>Objective</h4>This double-blind, multicenter, parallel-group, phase III study aimed to establish equivalent efficacy between CT-P16 and European Union-approved reference bevacizumab (EU-bevacizumab) in patients with metastatic or recurrent non-squamous non-small cell lung cancer (nsNSCLC).<h4>Patients and methods</h4>Patients with stage IV or recurrent nsNSCLC were randomized (1:1) to receive CT-P16 or EU-bevacizumab (15 mg/kg e ...[more]

PMID: 36169807

Similar Datasets

Project description:PurposeTo compare pharmacokinetics, safety, tolerability, and immunogenicity between SB8, a bevacizumab biosimilar, and the European Union (EU) and United States (US) reference products (bevacizumab-EU, bevacizumab-US).MethodsIn this randomized, double-blind, parallel-group, and single-dose study, healthy volunteers were randomized to receive a 3 mg/kg dose of SB8, bevacizumab-EU, or bevacizumab-US via intravenous infusion. Primary endpoints were area under the concentration-time curve from time zero to infinity (AUCinf) and to the last quantifiable concentration (AUClast), and maximum observed serum concentration (Cmax). Bioequivalence was achieved if 90% confidence intervals (CIs) for the ratios of the geometric least squares means (LSMeans) of primary endpoints were within the predefined bioequivalence margins of 80.00-125.00%. Safety and immunogenicity were also investigated.ResultsThe 90% CIs for the geometric LSMean ratios of AUCinf, AUClast and Cmax were all within the prespecified bioequivalence margins. Geometric LSMean ratios for SB8/bevacizumab-EU, SB8/bevacizumab-US and bevacizumab-EU/bevacizumab-US were 88.01%, 88.48% and 100.54% for AUCinf, 88.65%, 89.08% and 100.49% for AUClast and 99.59%, 101.15% and 101.56% for Cmax, respectively. Incidence of treatment-emergent adverse events (TEAEs) across treatment groups was comparable (SB8: 50.0%, bevacizumab-EU: 37.5%, bevacizumab-US: 53.8%). Most TEAEs were mild and considered as not related to the study drug. No deaths or treatment discontinuations due to adverse events occurred. Incidence of anti-drug antibodies was also comparable between all groups and no neutralizing antibodies were detected.ConclusionThis study demonstrated pharmacokinetic bioequivalence and similar safety and immunogenicity profiles of SB8 to both reference products, bevacizumab-EU and bevacizumab-US, and of bevacizumab-EU to bevacizumab-US. CLINICALTRIALS.Gov identifierNCT02453672 (submitted date); EudraCT number: 2015-001,026-41.

Project description:BackgroundBevacizumab-awwb (MVASI®) was the first U.S. Food and Drug Administration-approved biosimilar to Avastin® (reference product [RP]) for the treatment of several different types of cancers, including metastatic colorectal cancer (mCRC), an indication approved based on extrapolation.ObjectivesEvaluate treatment outcomes in mCRC patients who received first-line (1L) bevacizumab-awwb at treatment initiation or as continuing bevacizumab therapy (switched from RP).DesignA retrospective chart review study.MethodsAdult patients who had a confirmed diagnosis of mCRC (initial presentation of CRC on or after 01 January 2018) and initiated 1L bevacizumab-awwb between 19 July 2019 and 30 April 2020 were identified from the ConcertAI Oncology Dataset. A chart review was conducted to evaluate patient baseline clinical characteristics and effectiveness and tolerability outcomes during the follow-up. Study measures were reported stratified by prior use of RP: (1) naïve patients and (2) switchers (patients who switched to bevacizumab-awwb from RP without advancing the line of therapy).ResultsAt the end of study period, naïve patients (n = 129) had a median 1L progression-free survival (PFS) of 8.6 months [95% confidence interval (CI), 7.6-9.9] and a 12-month overall survival (OS) probability of 71.4% (95% CI, 61.0-79.5%). Switchers (n = 105) had a median 1L PFS of 14.1 months (95% CI, 12.1-15.8) and a 12-month OS probability of 87.6% (95% CI, 79.1-92.8%). During treatment with bevacizumab-awwb, 20 events of interest (EOIs) were reported in 18 naïve patients (14.0%) and 4 EOIs reported in 4 switchers (3.8%), of which the most commonly reported events were thromboembolic and hemorrhagic events. Most EOIs resulted in emergency department visit and/or treatment hold/discontinuation/switch. None of the EOIs resulted in death.ConclusionIn this real-world cohort of mCRC patients who were treated 1L with a bevacizumab biosimilar (bevacizumab-awwb), the clinical effectiveness and tolerability data were as expected and consistent with previously published findings from real-world studies of bevacizumab RP in mCRC patients.

Project description:BackgroundBCD-021 is a bevacizumab biosimilar which was shown to be equivalent to reference bevacizumab in a wide panel of physicochemical studies as well as preclinical studies in vitro and in vivo. International multicenter phase III clinical trial was conducted to compare efficacy and safety of BCD-021 and reference bevacizumab in combination with paclitaxel and carboplatin in a first-line treatment of inoperable or advanced non-squamous non-small-cell lung cancer (NSCLC).MethodsPatients with no previous treatment for advanced non-squamous NSCLC were randomly assigned 3:2 to BCD-021 or reference bevacizumab and were treated with bevacizumab + paclitaxel + carboplatin. Therapy continued for 6 cycles (every 3 weeks), until progression of the disease or unbearable toxicity. The primary study endpoint was the overall response rate. The study goal was to prove the equivalent efficacy of BCD-021 and reference bevacizumab. Equivalence margins for 95% CI for the difference in the overall response rates were set at [-18%; 18%], for 90% CI for the ratio of overall response rate were set at [67%; 150%].ResultsIn total 357 patients were enrolled in the study, 212 in the BCD-021 group and 145 in the reference bevacizumab group. The ORR was 34.63% in the BCD-022 group and 33.82% in the reference bevacizumab group. Limits of 95% CI for the difference in overall response rates between the groups were [-9.47%; 11.09%]. Limits of 90% CI for the ratio of overall response rate between the groups were [79.6%; 131.73%]. For both approaches CI lied within predetermined equivalence margins. Profile of adverse events (AEs) was similar between the groups (any AEs were reported in 86.89% of patients in BCD-021 group and 89.05% of patients in reference group). No unexpected adverse reactions were reported throughout the study. No statistically significant differences regarding anti-drug antibody occurrence rate was found between BCD-022 (n=4; 1.96%) and comparator (n=5; 3.65%). Both drug products showed low occurrence rate and short life of anti-bevacizumab antibodies. Pharmacokinetics assessment after 1st and 6th study drug injection also demonstrated equivalent PK parameters by all outcome measures.ConclusionsThus, the results of this study demonstrated therapeutic equivalence of bevacizumab biosimilar BCD-021 and referent bevacizumab drug.Trial registrationThe trial was registered with ClinicalTrials.gov (Study Number NCT01763645, date of registration 09/01/2013).

Project description:This 78-week (18-month) study conducted in 479 postmenopausal women with osteoporosis evaluated the efficacy, pharmacodynamics, pharmacokinetics, safety, and immunogenicity of candidate biosimilar CT-P41 relative to US reference denosumab. CT-P41 had equivalent efficacy and pharmacodynamics to US-denosumab, with similar pharmacokinetics and comparable safety and immunogenicity profiles.PurposeTo demonstrate equivalence of candidate biosimilar CT-P41 and US reference denosumab (US-denosumab) in postmenopausal women with osteoporosis.MethodsThis 78-week (18-month), double-blind, randomized, active-controlled Phase 3 study (NCT04757376) comprised two treatment periods (TPs). In TPI, patients (N = 479) were randomized 1:1 to 60 mg subcutaneous CT-P41 or US-denosumab. At Week 52, those who had received CT-P41 in TPI continued to do so. Those who had received US-denosumab were randomized (1:1) to continue treatment or switch to CT-P41 in TPII. The primary efficacy endpoint was percent change from baseline in lumbar spine bone mineral density at Week 52. Efficacy equivalence was concluded if associated 95% confidence intervals (CI) for least squares (LS) mean group differences fell within ± 1.503%. The primary pharmacodynamic (PD) endpoint was area under the effect curve for serum carboxy-terminal cross-linking telopeptide of type I collagen through the first 26 weeks, with an equivalence margin of 80-125% (for 95% CIs associated with geometric LS mean ratios).ResultsEquivalence was demonstrated for CT-P41 and US-denosumab with respect to primary efficacy (LS mean difference [95% CI]: - 0.139 [- 0.826, 0.548] in the full analysis set and - 0.280 [- 0.973, 0.414] in the per-protocol set) and PD (geometric LS mean ratio [95% CI]: 94.94 [90.75, 99.32]) endpoints. Secondary efficacy, PD, pharmacokinetics, and safety results were comparable among all groups up to Week 78, including after transitioning to CT-P41 from US-denosumab.ConclusionsCT-P41 was equivalent to US-denosumab in women with postmenopausal osteoporosis, with respect to primary efficacy and PD endpoints.

Dataset Information

Candidate Bevacizumab Biosimilar CT-P16 versus European Union Reference Bevacizumab in Patients with Metastatic or Recurrent Non-Small Cell Lung Cancer: A Randomized Controlled Trial.

Background

Objective

Patients and methods

Results

Conclusions

Trial registration number

Publications

Candidate Bevacizumab Biosimilar CT-P16 versus European Union Reference Bevacizumab in Patients with Metastatic or Recurrent Non-Small Cell Lung Cancer: A Randomized Controlled Trial.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets