TROIKA‐1: A double‐blind, randomized, parallel group, study aimed to demonstrate the equivalent pharmacokinetic profile of HD201, a potential biosimilar candidate to trastuzumab, versus EU‐Herceptin<sup>®</sup> and US‐Herceptin<sup>®</sup> in healthy male subjects

Demarchi, Martin; Coliat, Pierre; Mclendon, Kristi; Hii, Jocelyn; Feyaerts, Peggy; Ang, Felicia; Jaison, Litha; Deforce, Filip; Derde, Marie-Paule; Kim, Michael Jinwoo; Park, Lisa Soyeon; Detappe, Alexandre; Pivot, Xavier

doi:10.1002/prp2.839

Cited by 4 publications

(7 citation statements)

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“…The clinical demonstration of PK equivalence in healthy participants between HD201 and referent trastuzumab sourced from the US and European Union was established. 5 Additional PK assessment for patients who are receiving iterative cycles of trastuzumab is required and was part of the TROIKA study. 3 Assessment of C trough at cycles 5 and/or 8 established equivalence, which is relevant because a C trough value higher than the threshold of biological activity is the key PK parameter for consideration.…”

Section: Discussionmentioning

confidence: 99%

“…During development, to justify the changes in the manufacturing process in addition to the previously reported phase I study in healthy participants, a second phase I study that demonstrated pharmacokinetic equivalence was conducted. 4,5 The aim of the present TROIKA study represents the ultimate step and is designed to show similar efficacy and safety between HD201 and referent trastuzumab in patients with ERBB2-positive early breast cancer. The primary objective was to demonstrate the equivalent clinical efficacy in terms of the total pathological complete response (tpCR) rate assessed at the time of surgery.…”

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confidence: 99%

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Efficacy of HD201 vs Referent Trastuzumab in Patients With ERBB2-Positive Breast Cancer Treated in the Neoadjuvant Setting

Pivot

Георгиевич

Shamrai³

et al. 2022

JAMA Oncol

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IMPORTANCEThe drug HD201 is a biosimilar candidate for breast cancer treatment as the reference trastuzumab.OBJECTIVE To compare the efficacy of HD201 with referent trastuzumab.DESIGN, SETTING, AND PARTICIPANTS This randomized clinical trial (TROIKA) included 502 women with ERBB2-positive early breast cancer treated with either HD201 or referent trastuzumab. It was conducted across 70 centers in 12 countries, including Western and Eastern Europe and Asian countries. Randomization was stratified by tumor hormone receptor status, clinical stage, and geographic region of recruitment. This analysis was conducted on February 12, 2021, after the completion of the adjuvant phase at a median of 31 months (IQR, 28-33 months) of follow-up.INTERVENTIONS Patients with ERBB2-positive early breast cancer were randomly assigned to receive HD201 or referent trastuzumab in the neoadjuvant setting for 8 cycles, concurrently with 4 cycles of docetaxel, which was followed by 4 cycles of epirubicin and cyclophosphamide. Patients then underwent surgery, which was followed by treatment with 10 cycles of adjuvant HD201 or referent trastuzumab. MAIN OUTCOME AND MEASURESThe primary end point was the total pathological complete response (tpCR) assessed after neoadjuvant treatment. Equivalence was concluded if the 95% CI of the absolute difference in tpCR between arms in the per-protocol set was within the margin of more or less than 15%. Other objectives included the breast pathological complete response, overall response, event-free and overall survival, safety, pharmacokinetics, and immunogenicity.RESULTS A total of 502 female patients (mean [range] age, 53 [26-82] years) were randomized to receive either HD201 or referent trastuzumab, and 474 (94.2%) were eligible for inclusion in the per-protocol set. The baseline characteristics were well balanced between the 2 arms; 195 tumors (38.8%) were hormone receptor-negative , and 213 patients (42.4%) had clinical stage III disease. The tpCR rates were 45% and 48.7% for HD201 and referent trastuzumab, respectively. The difference between the 2 groups was not significant at −3.8% (95% CI, −12.8% to 5.4%) and fell within the predefined equivalence margins. The ratio of the tpCR rates between the 2 arms was 0.92 (95% CI, 0.76 to 1.12). A total of 433 patients (86.1%) presented with 2232 treatment-emergent adverse events of special interest for trastuzumab during the entire treatment period, with 220 (88.0%) and 213 (84.5%) patients in the HD201 and referent trastuzumab groups, respectively. CONCLUSIONS AND RELEVANCEThe results of this randomized clinical trial found that HD201 demonstrated equivalence to referent trastuzumab in terms of efficacy for the end point of tpCR, with a similar safety profile.

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Section: Discussionmentioning

confidence: 99%

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confidence: 99%

Efficacy of HD201 vs Referent Trastuzumab in Patients With ERBB2-Positive Breast Cancer Treated in the Neoadjuvant Setting

Pivot

Георгиевич

Shamrai³

et al. 2022

JAMA Oncol

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“…Demarchi et al [ 61 ] also conducted a phase I study in healthy individuals to demonstrate pharmacokinetic equivalence. The main objective was to demonstrate the equivalence of HD201, EU-Herceptin ® , and US-Herceptin ® .…”

Section: Resultsmentioning

confidence: 99%

Systematic Review on the Use of Biosimilars of Trastuzumab in HER2+ Breast Cancer

Triantafyllidi

Triantafillidis

2022

Biomedicines

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Trastuzumab is a monoclonal antibody used in the treatment of breast cancer in cases where the tumor overexpresses the HER2 receptor, a cell membrane receptor activated by the epidermal growth factor. Intravenous and subcutaneous administration of trastuzumab have comparable clinical and pharmacological characteristics, but trastuzumab biosimilars are currently only available in intravenous form. Trastuzumab biosimilars are ultimately preferred by a proportion of patients, especially in cases where co-administration of other chemotherapeutic agents, such as trastuzumab and tucatinib, a small molecule of tyrosine kinase inhibitor, is required in patients with HER-positive metastatic breast cancer. Oncologists should be well-aware of the advantages of intravenously administered trastuzumab biosimilars over subcutaneous administration, certainly also taking into account the patient’s preferences. Further cost-effectiveness analyses will be very important, along with expectations regarding successful concomitant subcutaneous administration of trastuzumab with other anticancer drugs, such as pertuzumab. This systematic review describes and analyzes the so-far published studies concerning the use of the available trastuzumab biosimilars in HER-positive early and metastatic breast cancer in terms of efficacy, safety, and cost–benefit ratio. An attempt was also made to draw some conclusions and to comment on future needs and perspectives.

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Section: Discussionmentioning

confidence: 99%

“…This is consistent with previous studies, and these data support the continued development of the test drug as a biological drug candidate similar to the reference drug (Table S4). [11][12][13][14][15][16][17][18][19][20] Immunogenicity analysis showed that all time points in the reference group and other time points in the test group were negative for ADA except for one weak positive case in the test group before administration. The results are similar to those of other biosimilar studies, suggesting that these two drugs have low immunogenicity (see Table S4).…”

Section: Discussionmentioning

confidence: 99%

A Randomized, Single‐dose, Phase I Clinical Comparison of a Trastuzumab Biosimilar With a Reference Trastuzumab Formulation in Healthy Chinese Male Volunteers

Jia

Zhao

et al. 2022

Clinical Pharm in Drug Dev

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The test drug, a recombinant humanized monoclonal antibody, is a biosimilar candidate for the reference drug. The purpose of this study was to evaluate the bioequivalence of these two drugs. The study was divided into two parts, a pre‐study and a formal trial. The pre‐study included two subjects who were each given a single intravenous infusion of 6 mg/kg test drug. The formal trial was designed to be a randomized, double‐blind, parallel controlled trial in which 70 subjects were randomly assigned 1:1 to receive either test or reference drug as a single 6 mg/kg intravenous infusion. In the pre‐study, the immunogenicity was negative in both subjects and the safety of the test drug was considered to be good. The two groups in the formal trial had similar demographic characteristics. The 90% confidence interval of geometric mean ratios of area under the serum concentration‐time curve from the time 0 to the time of last quantifiable concentration, area under the serum concentration‐curve from time 0 to infinity, and maximum observed serum concentration between the test group and the reference group fell between 80% and 125% and the bioequivalence was recognized. There was no significant difference in the positive rate of antidrug antibodies. The treatment‐emergent adverse events in the test group were similar to those in the reference group. This study showed that the test drug has similar pharmacokinetics, immunogenicity, and safety to the reference drug in healthy male subjects.

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TROIKA‐1: A double‐blind, randomized, parallel group, study aimed to demonstrate the equivalent pharmacokinetic profile of HD201, a potential biosimilar candidate to trastuzumab, versus EU‐Herceptin^® and US‐Herceptin^® in healthy male subjects

Abstract: This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

Cited by 4 publications

References 13 publications

Efficacy of HD201 vs Referent Trastuzumab in Patients With ERBB2-Positive Breast Cancer Treated in the Neoadjuvant Setting

Efficacy of HD201 vs Referent Trastuzumab in Patients With ERBB2-Positive Breast Cancer Treated in the Neoadjuvant Setting

Systematic Review on the Use of Biosimilars of Trastuzumab in HER2+ Breast Cancer

A Randomized, Single‐dose, Phase I Clinical Comparison of a Trastuzumab Biosimilar With a Reference Trastuzumab Formulation in Healthy Chinese Male Volunteers

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TROIKA‐1: A double‐blind, randomized, parallel group, study aimed to demonstrate the equivalent pharmacokinetic profile of HD201, a potential biosimilar candidate to trastuzumab, versus EU‐Herceptin® and US‐Herceptin® in healthy male subjects

Abstract: This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

Cited by 4 publications

References 13 publications

Efficacy of HD201 vs Referent Trastuzumab in Patients With ERBB2-Positive Breast Cancer Treated in the Neoadjuvant Setting

Efficacy of HD201 vs Referent Trastuzumab in Patients With ERBB2-Positive Breast Cancer Treated in the Neoadjuvant Setting

Systematic Review on the Use of Biosimilars of Trastuzumab in HER2+ Breast Cancer

A Randomized, Single‐dose, Phase I Clinical Comparison of a Trastuzumab Biosimilar With a Reference Trastuzumab Formulation in Healthy Chinese Male Volunteers

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TROIKA‐1: A double‐blind, randomized, parallel group, study aimed to demonstrate the equivalent pharmacokinetic profile of HD201, a potential biosimilar candidate to trastuzumab, versus EU‐Herceptin^® and US‐Herceptin^® in healthy male subjects