Efficacy, pharmacokinetics, and safety of the biosimilar CT-P10 in comparison with rituximab in patients with previously untreated low-tumour-burden follicular lymphoma

a randomised, double-blind, parallel-group, phase 3 trial

Michinori Ogura, Juan Manuel Sancho, Seok Goo Cho, Hideyuki Nakazawa, Junji Suzumiya, Gayane Tumyan, Jinseok Kim, Anne Lennard, José Mariz, Nikolai Ilyin, Wojciech Jurczak, Aurelio Lopez Martinez, Olga Samoilova, Edvard Zhavrid, Eduardo Yañez Ruiz, Marek Trneny, Leslie Popplewell, Bertrand Coiffier, Christian Buske, Won Seog Kim & 4 others Sang Joon Lee, Sung Young Lee, Yun Ju Bae, Larry W. Kwak

Research output: Contribution to journalArticle

8 Citations (Scopus)

Abstract

Background: Studies in patients with rheumatoid arthritis and advanced follicular lymphoma have shown that CT-P10, a rituximab biosimilar, has equivalent or non-inferior efficacy and pharmacokinetics to rituximab. We aimed to assess the therapeutic equivalence of single-agent CT-P10 and rituximab in patients with newly diagnosed low-tumour burden follicular lymphoma. Methods: In this ongoing, randomised, double-blind, parallel-group, active-controlled, phase 3 trial, adult patients (≥18 years) with stage II–IV low-tumour-burden follicular lymphoma were randomly assigned (1:1) using an interactive web or voice response system stratified by region, stage, and age to CT-P10 or US-sourced rituximab. Patients received CT-P10 or rituximab (375 mg/m2 intravenous) on day 1 of four 7-day cycles (induction period). Patients who had disease control after the induction period continued to a maintenance period of CT-P10 or rituximab administered every 8 weeks for six cycles and, if completed, a second year of maintenance therapy of additional CT-P10 (every 8 weeks for six cycles) was offered. The study was partially unmasked after database lock (Feb 23, 2018) for all data up to 7 months (before cycle 3 of the maintenance period). The primary endpoint was the proportion of patients who achieved an overall response by 7 months in the intention-to-treat population. Efficacy equivalence was shown if the two-sided 90% CIs for the treatment difference in the proportion of responders between CT-P10 and rituximab was within the equivalence margin of 17%. This trial is registered with ClinicalTrials.gov, number NCT02260804. Findings: Between Nov 9, 2015, and Jan 4, 2018, 402 patients were assessed for eligibility, of whom 258 were randomly assigned: 130 to CT-P10 and 128 to rituximab. 108 (83%) of 130 patients assigned to CT-P10 and 104 (81%) of 128 assigned to rituximab achieved an overall response by month 7 (treatment difference estimate 1·8%; 90% CI −6·43 to 10·20). Therapeutic equivalence was shown (90% CIs were within the prespecified margin of 17%). The most common grade 3 or 4 treatment-emergent adverse events were decreased neutrophil count (two grade 3 in the CT-P10 group) and neutropenia (one in each group); all other grade 3 or 4 treatment-emergent adverse events occurred in one patient each. Six (5%) of 130 patients who received CT-P10 and three (2%) of 128 who received rituximab experienced at least one treatment-emergent serious adverse event. Interpretation: CT-P10 was equivalent to rituximab in terms of efficacy and was well tolerated. CT-P10 monotherapy is suggested as a new therapeutic option for patients with low-tumour-burden follicular lymphoma. Funding: Celltrion, Inc.

Original languageEnglish
Pages (from-to)e543-e553
JournalThe Lancet Haematology
Volume5
Issue number11
DOIs
Publication statusPublished - 2018 Nov 1

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Biosimilar Pharmaceuticals
Follicular Lymphoma
Tumor Burden
Pharmacokinetics
Safety
Therapeutics
Rituximab
Maintenance

All Science Journal Classification (ASJC) codes

  • Hematology

Cite this

Ogura, Michinori ; Sancho, Juan Manuel ; Cho, Seok Goo ; Nakazawa, Hideyuki ; Suzumiya, Junji ; Tumyan, Gayane ; Kim, Jinseok ; Lennard, Anne ; Mariz, José ; Ilyin, Nikolai ; Jurczak, Wojciech ; Lopez Martinez, Aurelio ; Samoilova, Olga ; Zhavrid, Edvard ; Yañez Ruiz, Eduardo ; Trneny, Marek ; Popplewell, Leslie ; Coiffier, Bertrand ; Buske, Christian ; Kim, Won Seog ; Lee, Sang Joon ; Lee, Sung Young ; Bae, Yun Ju ; Kwak, Larry W. / Efficacy, pharmacokinetics, and safety of the biosimilar CT-P10 in comparison with rituximab in patients with previously untreated low-tumour-burden follicular lymphoma : a randomised, double-blind, parallel-group, phase 3 trial. In: The Lancet Haematology. 2018 ; Vol. 5, No. 11. pp. e543-e553.
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title = "Efficacy, pharmacokinetics, and safety of the biosimilar CT-P10 in comparison with rituximab in patients with previously untreated low-tumour-burden follicular lymphoma: a randomised, double-blind, parallel-group, phase 3 trial",
abstract = "Background: Studies in patients with rheumatoid arthritis and advanced follicular lymphoma have shown that CT-P10, a rituximab biosimilar, has equivalent or non-inferior efficacy and pharmacokinetics to rituximab. We aimed to assess the therapeutic equivalence of single-agent CT-P10 and rituximab in patients with newly diagnosed low-tumour burden follicular lymphoma. Methods: In this ongoing, randomised, double-blind, parallel-group, active-controlled, phase 3 trial, adult patients (≥18 years) with stage II–IV low-tumour-burden follicular lymphoma were randomly assigned (1:1) using an interactive web or voice response system stratified by region, stage, and age to CT-P10 or US-sourced rituximab. Patients received CT-P10 or rituximab (375 mg/m2 intravenous) on day 1 of four 7-day cycles (induction period). Patients who had disease control after the induction period continued to a maintenance period of CT-P10 or rituximab administered every 8 weeks for six cycles and, if completed, a second year of maintenance therapy of additional CT-P10 (every 8 weeks for six cycles) was offered. The study was partially unmasked after database lock (Feb 23, 2018) for all data up to 7 months (before cycle 3 of the maintenance period). The primary endpoint was the proportion of patients who achieved an overall response by 7 months in the intention-to-treat population. Efficacy equivalence was shown if the two-sided 90{\%} CIs for the treatment difference in the proportion of responders between CT-P10 and rituximab was within the equivalence margin of 17{\%}. This trial is registered with ClinicalTrials.gov, number NCT02260804. Findings: Between Nov 9, 2015, and Jan 4, 2018, 402 patients were assessed for eligibility, of whom 258 were randomly assigned: 130 to CT-P10 and 128 to rituximab. 108 (83{\%}) of 130 patients assigned to CT-P10 and 104 (81{\%}) of 128 assigned to rituximab achieved an overall response by month 7 (treatment difference estimate 1·8{\%}; 90{\%} CI −6·43 to 10·20). Therapeutic equivalence was shown (90{\%} CIs were within the prespecified margin of 17{\%}). The most common grade 3 or 4 treatment-emergent adverse events were decreased neutrophil count (two grade 3 in the CT-P10 group) and neutropenia (one in each group); all other grade 3 or 4 treatment-emergent adverse events occurred in one patient each. Six (5{\%}) of 130 patients who received CT-P10 and three (2{\%}) of 128 who received rituximab experienced at least one treatment-emergent serious adverse event. Interpretation: CT-P10 was equivalent to rituximab in terms of efficacy and was well tolerated. CT-P10 monotherapy is suggested as a new therapeutic option for patients with low-tumour-burden follicular lymphoma. Funding: Celltrion, Inc.",
author = "Michinori Ogura and Sancho, {Juan Manuel} and Cho, {Seok Goo} and Hideyuki Nakazawa and Junji Suzumiya and Gayane Tumyan and Jinseok Kim and Anne Lennard and Jos{\'e} Mariz and Nikolai Ilyin and Wojciech Jurczak and {Lopez Martinez}, Aurelio and Olga Samoilova and Edvard Zhavrid and {Ya{\~n}ez Ruiz}, Eduardo and Marek Trneny and Leslie Popplewell and Bertrand Coiffier and Christian Buske and Kim, {Won Seog} and Lee, {Sang Joon} and Lee, {Sung Young} and Bae, {Yun Ju} and Kwak, {Larry W.}",
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Ogura, M, Sancho, JM, Cho, SG, Nakazawa, H, Suzumiya, J, Tumyan, G, Kim, J, Lennard, A, Mariz, J, Ilyin, N, Jurczak, W, Lopez Martinez, A, Samoilova, O, Zhavrid, E, Yañez Ruiz, E, Trneny, M, Popplewell, L, Coiffier, B, Buske, C, Kim, WS, Lee, SJ, Lee, SY, Bae, YJ & Kwak, LW 2018, 'Efficacy, pharmacokinetics, and safety of the biosimilar CT-P10 in comparison with rituximab in patients with previously untreated low-tumour-burden follicular lymphoma: a randomised, double-blind, parallel-group, phase 3 trial', The Lancet Haematology, vol. 5, no. 11, pp. e543-e553. https://doi.org/10.1016/S2352-3026(18)30157-1

Efficacy, pharmacokinetics, and safety of the biosimilar CT-P10 in comparison with rituximab in patients with previously untreated low-tumour-burden follicular lymphoma : a randomised, double-blind, parallel-group, phase 3 trial. / Ogura, Michinori; Sancho, Juan Manuel; Cho, Seok Goo; Nakazawa, Hideyuki; Suzumiya, Junji; Tumyan, Gayane; Kim, Jinseok; Lennard, Anne; Mariz, José; Ilyin, Nikolai; Jurczak, Wojciech; Lopez Martinez, Aurelio; Samoilova, Olga; Zhavrid, Edvard; Yañez Ruiz, Eduardo; Trneny, Marek; Popplewell, Leslie; Coiffier, Bertrand; Buske, Christian; Kim, Won Seog; Lee, Sang Joon; Lee, Sung Young; Bae, Yun Ju; Kwak, Larry W.

In: The Lancet Haematology, Vol. 5, No. 11, 01.11.2018, p. e543-e553.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Efficacy, pharmacokinetics, and safety of the biosimilar CT-P10 in comparison with rituximab in patients with previously untreated low-tumour-burden follicular lymphoma

T2 - a randomised, double-blind, parallel-group, phase 3 trial

AU - Ogura, Michinori

AU - Sancho, Juan Manuel

AU - Cho, Seok Goo

AU - Nakazawa, Hideyuki

AU - Suzumiya, Junji

AU - Tumyan, Gayane

AU - Kim, Jinseok

AU - Lennard, Anne

AU - Mariz, José

AU - Ilyin, Nikolai

AU - Jurczak, Wojciech

AU - Lopez Martinez, Aurelio

AU - Samoilova, Olga

AU - Zhavrid, Edvard

AU - Yañez Ruiz, Eduardo

AU - Trneny, Marek

AU - Popplewell, Leslie

AU - Coiffier, Bertrand

AU - Buske, Christian

AU - Kim, Won Seog

AU - Lee, Sang Joon

AU - Lee, Sung Young

AU - Bae, Yun Ju

AU - Kwak, Larry W.

PY - 2018/11/1

Y1 - 2018/11/1

N2 - Background: Studies in patients with rheumatoid arthritis and advanced follicular lymphoma have shown that CT-P10, a rituximab biosimilar, has equivalent or non-inferior efficacy and pharmacokinetics to rituximab. We aimed to assess the therapeutic equivalence of single-agent CT-P10 and rituximab in patients with newly diagnosed low-tumour burden follicular lymphoma. Methods: In this ongoing, randomised, double-blind, parallel-group, active-controlled, phase 3 trial, adult patients (≥18 years) with stage II–IV low-tumour-burden follicular lymphoma were randomly assigned (1:1) using an interactive web or voice response system stratified by region, stage, and age to CT-P10 or US-sourced rituximab. Patients received CT-P10 or rituximab (375 mg/m2 intravenous) on day 1 of four 7-day cycles (induction period). Patients who had disease control after the induction period continued to a maintenance period of CT-P10 or rituximab administered every 8 weeks for six cycles and, if completed, a second year of maintenance therapy of additional CT-P10 (every 8 weeks for six cycles) was offered. The study was partially unmasked after database lock (Feb 23, 2018) for all data up to 7 months (before cycle 3 of the maintenance period). The primary endpoint was the proportion of patients who achieved an overall response by 7 months in the intention-to-treat population. Efficacy equivalence was shown if the two-sided 90% CIs for the treatment difference in the proportion of responders between CT-P10 and rituximab was within the equivalence margin of 17%. This trial is registered with ClinicalTrials.gov, number NCT02260804. Findings: Between Nov 9, 2015, and Jan 4, 2018, 402 patients were assessed for eligibility, of whom 258 were randomly assigned: 130 to CT-P10 and 128 to rituximab. 108 (83%) of 130 patients assigned to CT-P10 and 104 (81%) of 128 assigned to rituximab achieved an overall response by month 7 (treatment difference estimate 1·8%; 90% CI −6·43 to 10·20). Therapeutic equivalence was shown (90% CIs were within the prespecified margin of 17%). The most common grade 3 or 4 treatment-emergent adverse events were decreased neutrophil count (two grade 3 in the CT-P10 group) and neutropenia (one in each group); all other grade 3 or 4 treatment-emergent adverse events occurred in one patient each. Six (5%) of 130 patients who received CT-P10 and three (2%) of 128 who received rituximab experienced at least one treatment-emergent serious adverse event. Interpretation: CT-P10 was equivalent to rituximab in terms of efficacy and was well tolerated. CT-P10 monotherapy is suggested as a new therapeutic option for patients with low-tumour-burden follicular lymphoma. Funding: Celltrion, Inc.

AB - Background: Studies in patients with rheumatoid arthritis and advanced follicular lymphoma have shown that CT-P10, a rituximab biosimilar, has equivalent or non-inferior efficacy and pharmacokinetics to rituximab. We aimed to assess the therapeutic equivalence of single-agent CT-P10 and rituximab in patients with newly diagnosed low-tumour burden follicular lymphoma. Methods: In this ongoing, randomised, double-blind, parallel-group, active-controlled, phase 3 trial, adult patients (≥18 years) with stage II–IV low-tumour-burden follicular lymphoma were randomly assigned (1:1) using an interactive web or voice response system stratified by region, stage, and age to CT-P10 or US-sourced rituximab. Patients received CT-P10 or rituximab (375 mg/m2 intravenous) on day 1 of four 7-day cycles (induction period). Patients who had disease control after the induction period continued to a maintenance period of CT-P10 or rituximab administered every 8 weeks for six cycles and, if completed, a second year of maintenance therapy of additional CT-P10 (every 8 weeks for six cycles) was offered. The study was partially unmasked after database lock (Feb 23, 2018) for all data up to 7 months (before cycle 3 of the maintenance period). The primary endpoint was the proportion of patients who achieved an overall response by 7 months in the intention-to-treat population. Efficacy equivalence was shown if the two-sided 90% CIs for the treatment difference in the proportion of responders between CT-P10 and rituximab was within the equivalence margin of 17%. This trial is registered with ClinicalTrials.gov, number NCT02260804. Findings: Between Nov 9, 2015, and Jan 4, 2018, 402 patients were assessed for eligibility, of whom 258 were randomly assigned: 130 to CT-P10 and 128 to rituximab. 108 (83%) of 130 patients assigned to CT-P10 and 104 (81%) of 128 assigned to rituximab achieved an overall response by month 7 (treatment difference estimate 1·8%; 90% CI −6·43 to 10·20). Therapeutic equivalence was shown (90% CIs were within the prespecified margin of 17%). The most common grade 3 or 4 treatment-emergent adverse events were decreased neutrophil count (two grade 3 in the CT-P10 group) and neutropenia (one in each group); all other grade 3 or 4 treatment-emergent adverse events occurred in one patient each. Six (5%) of 130 patients who received CT-P10 and three (2%) of 128 who received rituximab experienced at least one treatment-emergent serious adverse event. Interpretation: CT-P10 was equivalent to rituximab in terms of efficacy and was well tolerated. CT-P10 monotherapy is suggested as a new therapeutic option for patients with low-tumour-burden follicular lymphoma. Funding: Celltrion, Inc.

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U2 - 10.1016/S2352-3026(18)30157-1

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