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Trastuzumab emtansine - CAS 1018448-65-1 Catalog number: BADC-00023
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Trastuzumab emtansine is an antibody-drug conjugate (ADC) consisting of the recombinant anti-epidermal growth factor receptor 2 (HER2) monoclonal antibody trastuzumab conjugated to the maytansinoid DM1 via a nonreducible thioether linkage (MCC) with potential antineoplastic activity. The trastuzumab moiety of this ADC binds to HER2 on tumor cell surface surfaces. Upon internalization, the DM1 moiety is released and binds to tubulin, thereby disrupting microtubule assembly/disassembly dynamics and inhibiting cell division and the proliferation of cancer cells that overexpress HER2. Linkage of antibody and drug through a nonreducible linker has been reported to contribute to the improved efficacy and reduced toxicity of this ADC compared to similar ADCs constructed with reducible linkers.
Category
ADCs Cytotoxin with Linkers
Product Name
Trastuzumab emtansine
CAS
1018448-65-1
Catalog Number
BADC-00023
Molecular Formula
C6448H9948N1720O2012S44·(C47H62ClN4O13S)n
Ordering Information
| Catalog Number | Size | Price | Quantity |
|---|---|---|---|
| BADC-00023 | 5 mg | $1554 |
Description
Trastuzumab emtansine is an antibody-drug conjugate (ADC) consisting of the recombinant anti-epidermal growth factor receptor 2 (HER2) monoclonal antibody trastuzumab conjugated to the maytansinoid DM1 via a nonreducible thioether linkage (MCC) with potential antineoplastic activity. The trastuzumab moiety of this ADC binds to HER2 on tumor cell surface surfaces. Upon internalization, the DM1 moiety is released and binds to tubulin, thereby disrupting microtubule assembly/disassembly dynamics and inhibiting cell division and the proliferation of cancer cells that overexpress HER2. Linkage of antibody and drug through a nonreducible linker has been reported to contribute to the improved efficacy and reduced toxicity of this ADC compared to similar ADCs constructed with reducible linkers.
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.
Clinical Trial Information
| 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 |
Purity
>98%
Shipping
Room temperature
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).
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