Trastuzumab (HERCEPTIN®)

Agent Description

Trastuzumab is a humanized IgG1 kappa monoclonal antibody that selectively binds with high affinity to the extracellular domain of the human epidermal growth factor receptor 2 protein, HER2. Trastuzumab is produced by recombinant DNA technology in a mammalian cell (Chinese Hamster Ovary) culture containing the antibiotic gentamicin. Gentamicin is not detectable in the final product.

Trastuzumab is a sterile, white to pale yellow, preservative-free lyophilized powder for intravenous administration. Each multi-use vial contains 440 mg trastuzumab, 400 mg α,α-trehalose dihydrate, 9.9 mg L-histidine HCl, 6.4 mg L-histidine, and 1.8 mg polysorbate 20, USP. Reconstitution with 20 mL of the appropriate diluent (BWFI or SWFI) yields a solution containing 21 mg/mL trastuzumab at a pH of approximately 6.

Mechanism of Action

The HER2 (or c-erbB2) proto-oncogene encodes a transmembrane receptor protein of 185 kDa, which is structurally related to the epidermal growth factor receptor. Trastuzumab has been shown, in both in vitro assays and in animals, to inhibit the proliferation of human tumor cells that overexpress HER2.

Trastuzumab is a mediator of antibody-dependent cellular cytotoxicity (ADCC). In vitro, trastuzumab-mediated ADCC has been shown to be preferentially exerted on HER2 overexpressing cancer cells compared with cancer cells that do not overexpress HER2.

Classification

Antineoplastic agent; a recombinant DNA-derived humanized anti-HER2 monoclonal antibody.

Molecular Targets

HER2/neu

Monograph

Approved Indications:

Trastuzumab is indicated for adjuvant treatment of HER2 overexpressing node positive or node negative (ER/PR negative or with one high risk feature) breast cancer
- as part of a treatment regimen consisting of doxorubicin, cyclophosphamide, and either paclitaxel or docetaxel
- with docetaxel and carboplatin
- as a single agent following multi-modality anthracycline based therapy
Trastuzumab is indicated in combination with paclitaxel for first-line treatment of HER2-overexpressing metastatic breast cancer
Trastuzumab is indicated as a single agent for treatment of HER2-overexpressing breast cancer in patients who have received one or more chemotherapy regimens for metastatic disease
Trastuzumab is indicated, in combination with cisplatin and capecitabine or 5-fluorouracil, for the treatment of patients with HER2 overexpressing metastatic gastric or gastroesophageal junction adenocarcinoma who have not received prior treatment for metastatic disease.

Package insert: https://www.gene.com/download/pdf/herceptin_prescribing.pdf

Studies of Interest

In general, study proposals listed below will NOT be supported:

Use of trastuzumab without pertuzumab
Combinations with bevacizumab
HER2 normal/low studies
Novel combinations in the absence of Phase I data
Short duration trials in early breast cancer of less than 52 weeks total treatment duration

Information collaborator would like included in investigator proposals

N/A

Genentech supports non-clinical research proposals through a separate mechanism. Please visit https://www.gene.com/gene/reagents-program/reagents-program.jsp if you wish to submit a request for a Genentech agent for non-clinical work.