FDA Approves Multi-Dose Vial of Trastuzumab Biosimilar

The FDA has approved a 420 mg multi-dose vial of trastuzumab-dttb (Ontruzant), a biosimilar referencing trastuzumab (Herceptin).

The FDA has approved a 420 mg multi-dose vial of trastuzumab-dttb (Ontruzant), a biosimilar referencing trastuzumab (Herceptin), according to Samsung Bioepis, the agent’s developer.1

Trastuzumab-dttb was already approved as a 150 mg single-dose vial by the FDA in January 2019 across all eligible indications, including adjuvant treatment of HER2-overexpressing breast cancer, metastatic breast cancer, and metastatic gastric cancer or gastroesophageal junction adenocarcinoma in patients who have not received prior treatment for metastatic disease.

The European Commission approved the biosimilar in November 2017. 

The biosimilar is indicated for adjuvant treatment of HER2-overexpressing node-positive or node-negative (ER/PR-negative or with one high-risk feature) breast cancer, including:

  • As part of a treatment regimen containing doxorubicin (Lipodox), cyclophosphamide, and either paclitaxel (Abraxane) or docetaxel (Taxotere).

  • With docetaxel and carboplatin (Paraplatin).

  • As a single agent following multi-modality anthracycline-based therapy.

Trastuzumab-dttb is also indicated in combination with paclitaxel for the first line treatment of HER2-overexpressing metastatic breast cancer or as a single agent for treatment of HER2-overexpressing breast cancer in patients who have received 1 or more chemotherapy regimens for metastatic disease. 

Additionally, trastuzumab-dttb is indicated in combination with cisplatin and capecitabine (Xeloda) or 5-fluorouracil (Fluoroplex) for the treatment of patients with HER2 overexpressing metastatic gastric gastroesophageal junction adenocarcinoma, who have not received prior treatment for metastatic disease. 

All eligible patients selected for therapy should be chosen based on an FDA-approved diagnostic for a trastuzumab product.

The most common adverse reactions for trastuzumab products in breast cancer treatment include fever, nausea, vomiting, infusion reactions, diarrhea, infections, increased cough, headache, fatigue, dyspnea, rash, neutropenia, anemia, and myalgia.

For metastatic breast cancer, common adverse reactions were neutropenia, diarrhea, fatigue, anemia, stomatitis, weight loss, upper respiratory tract infections, fever, thrombocytopenia, mucosal inflammation, nasopharyngitis, and dysgeusia. 

The approval was based on data sets from 7 clinical trials, which demonstrated similarity in survival outcomes and safety between the biosimilar and reference trastuzumab in patients with HER2-positive adjuvant and metastatic breast cancer, as well as HER2-positive metastatic gastric cancer.

Phase III data on the biosimilar were published in January 2018, in which trastuzumab-dttb inducted a rate of breast pathologic complete response similar to that of trastuzumab in patients with HER2-positive breast cancer, and also demonstrated comparable safety outcomes.2

Overall, 800 patients were randomized to 8 cycles of the biosimilar (n = 402) or trastuzumab (n = 398) from April 2014 to August 2015 concurrently with 4 cycles of docetaxel followed by 4 cycles of fluorouracil, epirubicin (Ellence), and cyclophosphamide. The subjects then underwent surgery, followed by 10 cycles of adjuvant trastuzumab-dttb or trastuzumab. 

No relevant differences were observed between the 2 arms in the mean values for the relative dose-intensity of both investigational and noninvestigational products. 


1. Samsung Bioepis Announces FDA Approval of 420 mg Multi-dose Vial of ONTRUZANT (trastuzumab-dttb) [news release]. Incheon, Korea. Published March 24, 2020. businesswire.com/news/home/20200324005274/en/. Accessed March 24, 2020. 

2. 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. doi:10.1200/JCO.2017.74.0126.