Name: Trastuzumab emtansine
Brand: BOC Sciences
Price: 1554 USD
Availability: MadeToOrder

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In Vitro

In vitro study showed that the level of HER2 expression had no correlation with the sensitivity to EGFR-TKI, erlotinib but showed some correlation with HER2-inhibitor, ado-trastuzumab emtansine (T-DM1) in multiple EGFR-mutant lung cancer cell lines. In addition, HER2 expression was increased in persister cancer cells in 11-18 cell line harboring EGFR L858R or HCC827 cell line harboring EGFR exon 19 deletion after the exposure to erlotinib in vitro and in vivo. The combination of erlotinib and T-DM1 showed a superior inhibitory effect on cell proliferation compared with those of the erlotinib or T-DM1 alone in either 11-18 or HCC827 cells in vitro. The combination therapy also induced a significantly greater inhibitory effect on tumor growth in xenograft model in mice transplanted with either 11-18 or HCC827 cells compared with erlotinib alone or T-DM1 alone. No body weight loss was observed in these mice. These results suggested that the combination therapy with EGFR-TKI and T-DM1 might be a potentially promising strategy for treating lung cancer harboring EGFR mutations.

In Vivo

Trastuzumab emtansine (T-DM1) targets the epidermal growth factor receptor 2 (HER2), highly expressed in the most aggressive forms of breast cancer. Current standard of care in HER2-positive advanced or metastatic breast cancers has its limitations, particularly after progression on HER2-targeted approved therapies. T-DM1 showed a significant antitumor activity in vitro and in vivo, and in experimental models resistant to HER2-targeted agents. Phase I and II studies showed that the maximum tolerated dose for T-DM1 is 3.6 mg/kg given intravenously every three weeks. At this recommended dose, T-DM1 provided objective tumor responses and favourable safety profile. A phase II randomised study, evaluating T-DM1 in first line vs trastuzumab plus docetaxel, the current standard of care in advanced or metastatic breast cancers, showed improved tolerability and efficacy. Recently, the results of EMILIA, a phase III randomised study assessing, after prior treatment with trastuzumab and a taxane, the efficacy and the safety of T-DM1 vs lapatinib plus capecitabine, confirmed the therapeutic benefit. T-DM1 appears to be an effective therapeutic option to treat patients with HER2-positive metastatic breast cancer.

NCT Number	Condition Or Disease	Phase	Start Date	Sponsor	Status
NCT02675829	Solid Tumor Cancers	Phase 2	2021-07-20	Memorial Sloan Kettering Cancer Center	Recruiting
NCT04439110	Advanced Lymphoma	Phase 2	2021-07-06	National Cancer Institute (NCI)	Active, not recruiting
NCT00951665	Metastatic Breast Cancer	Phase 1, Phase 2	2016-06-24	Genentech, Inc.	Completed
NCT02658084	Breast Cancer	Phase 1, Phase 2	2019-04-17	University of Miami	Terminated (Terminated due to low accrual and toxicity concerns.)
NCT01983501	HER2 Positive Breast Cancers	Phase 1	2020-09-21	Seagen Inc.	Completed

1.Telangiectasia and Pulmonary Arterial Hypertension Following Treatment With Trastuzumab Emtansine: A Case Report.

Kwon Y1, Gomberg-Maitland M2, Pritzker M1, Thenappan T3. Chest. 2016 Apr;149(4):e103-5. doi: 10.1016/j.chest.2015.09.008.

Trastuzumab emtansine (T-DM1) is a Food and Drug Administration-approved novel agent for the treatment of HER-2 positive advanced breast cancer. We report a case of pulmonary arterial hypertension (PAH) that we attribute to the use of T-DM1. A 43-year-old woman with stage IV breast cancer presented with dyspnea on exertion. After excluding other secondary causes of pulmonary hypertension, a diagnosis of moderately severe PAH was made based on right heart catheterization. History revealed that the patient had been on T-DM1 before presentation. During T-DM1 treatment, the patient experienced hereditary hemorrhagic telangiectasia-like symptoms consisting of spider angiomata-skin lesions, epistaxis, and hematochezia, which resolved with discontinuation of T-DM1. Temporal associations of T-DM1 use with the development of PAH in the patient, and the reported association between hereditary hemorrhagic telangiectasia and PAH via genetic linkage, led us to suspect T-DM1 as the cause of PAH.

2.Phase 1b/2a study of trastuzumab emtansine (T-DM1), paclitaxel, and pertuzumab in HER2-positive metastatic breast cancer.

Krop IE1, Modi S2,3, LoRusso PM4, Pegram M5, Guardino E6, Althaus B6, Lu D6, Strasak A7, Elias A8. Breast Cancer Res. 2016 Mar 15;18(1):34. doi: 10.1186/s13058-016-0691-7.

BACKGROUND: In pre-clinical studies, the anti-tumor activity of T-DM1 was enhanced when combined with taxanes or pertuzumab. This phase 1b/2a study evaluated the safety/tolerability of T-DM1 + paclitaxel ± pertuzumab in HER2-positive advanced breast cancer.

3.Safety and Efficacy of Trastuzumab Emtansine in Advanced Human Epidermal Growth Factor Receptor 2-Positive Breast Cancer: a Meta-analysis.

Shen K1, Ma X1, Zhu C1, Wu X1, Jia H1. Sci Rep. 2016 Mar 16;6:23262. doi: 10.1038/srep23262.

Advanced or metastatic breast cancer is an incurable disease with high mortality rate worldwide and about 20% of breast cancers overexpress and amplify the human epidermal growth factor receptor 2 (HER2). Achievements in targeted therapy have benefited people during the past decades. Trastuzumab emtansine (T-DM1), a novel antibody-drug conjugate playing a powerful role in anti-tumor activity, not only blocks the HER2 signaling pathways, but also disturbs the microtubule dynamics. To access the efficacy and safety of T-DM1, we analyzed 9 clinical trials on T-DM1. Results showed that fatigue (0.604, 95% CI 0.551, 0.654), nausea (0.450, 95% CI 0.365, 0.537), increased transaminases (0.425, 95% CI 0.353, 0.500) and thrombocytopenia (0.383, 95% CI 0.322, 0.448) occurred more frequently in participants with single T-DM1. In controlled trials, increased transaminases (OR = 4.040, 95% CI 1.429, 11.427), thrombocytopenia (OR = 8.500, 95% CI 3.964, 18.

4.Trastuzumab emtansine (T-DM1) plus docetaxel with or without pertuzumab in patients with HER2-positive locally advanced or metastatic breast cancer: Results from a phase Ib/IIa study.

Martin M1, Fumoleau P2, Dewar JA3, Albanell J4, Limentani SA5, Campone M6, Chang JC7, Patre M8, Strasak A9, de Haas SL10, Xu J11, Garcia-Saenz JA12. Ann Oncol. 2016 Apr 6. pii: mdw157. [Epub ahead of print]

BACKGROUND: Trastuzumab emtansine (T-DM1) exhibited enhanced antitumor activity when combined with docetaxel or pertuzumab in preclinical studies. This phase Ib/IIa study assessed the feasibility of T-DM1+docetaxel in patients with human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer (MBC) and T-DM1+docetaxel±pertuzumab in patients with HER2-positive locally advanced breast cancer (LABC).