FDA Approves New Dose of Biosimilar Ontruzant

The FDA has approved a new 420-mg multi-dose vial of Ontruzant a biosimilar of trastuzumab, according to a press release from Samsung Bioepis.

The FDA has approved a new 420-mg multi-dose vial of Ontruzant (SB3; trastuzumab-dttb), a biosimilar of trastuzumab (Herceptin), according to a press release from Samsung Bioepis.1

The biosimilar product was first approved by the FDA in January 2019 as a 150-mg single-dose vial for indications including in the adjuvant treatment of HER2-overexpressing breast cancer, metastatic breast cancer, and metastatic gastric or gastroesophageal junction cancer. It was also previously approved by the European Commission in November 2017.2

In December 2019, the agent also became thefirst biosimilar prequalified by the World Health Organizationfor the treatment of breast cancer.

Of the trials supporting the approval, SB3 was studied in a randomized, double-blind phase III trial in comparison with reference trastuzumab as a neoadjuvant therapy in patients with HER2-positive early breast cancer (NCT02149524). In this study, SB3 demonstrated biosimilarity with trastuzumab in terms of breast pathologic complete response (bpCR) rate.3

The trial enrolled 875 patients with newly diagnosed, early or locally advanced HER2-positive breast cancer. Patients were randomized to receive neoadjuvant intravenous SB3 or reference trastuzumab for 8 cycles given concurrently with chemotherapy before surgery and then another 10 cycles of adjuvant SB3 or trastuzumab. Eight hundred patients who completed neoadjuvant therapy and surgery were included in the per-protocol set.

Characteristics and demographics were similar between the 2 arms at baseline with no statistical differences noted. The median age overall was 51 years (range, 22-65) and most patients had T2 disease (52.8%) and clinically involved lymph nodes (79.5%). The mean left ventricular ejection fraction (LVEF) level was 65.24% at baseline.

Patients were eligible if they had an ECOG performance status of 0 to 1, baseline LVEF level of ≥55%, and known hormone receptor status. Exclusion criteria for the trial included a history of prior invasive breast cancer or other malignancy, prior cancer treatment, serious cardiac or pulmonary illness, HIV or hepatitis B or C virus, and other comorbid conditions requiring concurrent therapy.

The primary end point was bpCR rate and secondary measures included total pathological complete response rate (tpCR), overall clinical response rate, event-free survival, and overall survival. The study also explored pharmacokinetics and immunogenicity.

With SB3, the bpCR rate was 51.7% compared with 42.0% with trastuzumab in the per-protocol population. The adjusted rate of bpCR, 1.259, came within the predefined equivalence margins of the 95% confidence interval, achieving the primary end point of the trial. Notably, bpCR rates were higher in patients with hormone receptor—negative tumors than in those with either estrogen receptor or progesterone receptor–positive tumors.

The rate of tpCR was 45.8% and 35.8% for SB3 and trastuzumab, respectively, and the overall response rates were 96.3% and 91.2%.

Overall survival and event-free survival data were not mature at the time of data cutoff but pharmacokinetics were also within the predefined equivalence margins for similarity between the 2 arms.

Adverse events (AEs) were seen in similar quantities between the 2 arms with 96.6% of patients in the SB3 arm experiencing toxicity versus 95.2% in the trastuzumab arm. Serious AEs were seen in 10.5% and 10.7% of patients in the SB3 and trastuzumab arms, respectively.

Treatment-emergent AEs of special interest included infusion-related reactions, which occurred in 8.2% of patients in the SB3 arm and in 10% of the reference trastuzumab arm, asymptomatic left ventricular systolic dysfunction (0.9% vs 0.7%, respectively), and congestive heart failure (0.5% vs 0%). One death occurred in the SB3 arm compared with 3 in the control arm.

More specifically, SB3 is approved for the adjuvant treatment of patients with HER2-overexpressing node-positive breast cancer or node-negative breast cancer with one high-risk feature either with doxorubicin, cyclophosphamide, and paclitaxel or docetaxel; with docetaxel and carboplatin; or as a single-agent following multi-modality therapy with an anthracycline.

It is also approved for use in combination with paclitaxel for patients with previously untreated HER2-overexpressing metastatic breast cancer and as a monotherapy for patients with previously treated HER2-overexpressing metastatic breast cancer. In the setting of HER2-overexpressing metastatic gastric or gastroesophageal junction adenocarcinoma, the biosimilar is approved for use with cisplatin and capecitabine or 5-fluorouracil in patients who have not received prior therapy in the metastatic setting. All patients are to be selected for therapy with an FDA-approved companion diagnostic for a trastuzumab product.1


  1. Samsung Bioepis Announces FDA Approval of 420 mg Multi-dose Vial of ONTRUZANT (trastuzumab-dttb) [press release]. Incheon, Korea: Samsung Bioepis Co., Ltd.; March 24, 2020.https://bwnews.pr/2UyWTBy. Accessed March 24, 2020.
  2. US FDA Approves ONTRUZANT (trastuzumab-dttb), Samsung Bioepis’ First Oncology Medicine in the United States [press release]. Incheon, Korea: Samsung Bioepis Co., Ltd.; January 20, 2019. https://bwnews.pr/2UszqSs. Accessed March 24, 2020.
  3. Pivot X, Bondarenko I, Nowecki Z, et al. Phase III, Randomized, Double-Blind Study Comparing the Efficacy, Safety, and Immunogenicity of SB3 (Trastuzumab Biosimilar) and Reference Trastuzumab in Patients Treated With Neoadjuvant Therapy for Human Epidermal Growth Factor Receptor 2—Positive Early Breast Cancer.J Clin Oncol.2018;36(10):968-974. doi: 10.1200/JCO.2017.74.0126.
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