EMERGE : A Randomized Phase II Study of the Antibody-Drug Conjugate Glembatumumab Vedotin in Advanced Glycoprotein NMB-Expressing Breast Cancer
© 2015 by American Society of Clinical Oncology..
PURPOSE: Glycoprotein NMB (gpNMB), a negative prognostic marker, is overexpressed in multiple tumor types. Glembatumumab vedotin is a gpNMB-specific monoclonal antibody conjugated to the potent cytotoxin monomethyl auristatin E. This phase II study investigated the activity of glembatumumab vedotin in advanced breast cancer by gpNMB expression.
PATIENTS AND METHODS: Patients (n = 124) with refractory breast cancer that expressed gpNMB in ≥ 5% of epithelial or stromal cells by central immunohistochemistry were stratified by gpNMB expression (tumor, low stromal intensity, high stromal intensity) and were randomly assigned 2:1 to glembatumumab vedotin (n = 83) or investigator's choice (IC) chemotherapy (n = 41). The study was powered to detect overall objective response rate (ORR) in the glembatumumab vedotin arm between 10% (null) and 22.5% (alternative hypothesis) with preplanned investigation of activity by gpNMB distribution and/or intensity (Stratum 1 to Stratum 3).
RESULTS: Glembatumumab vedotin was well tolerated as compared with IC chemotherapy (less hematologic toxicity; more rash, pruritus, neuropathy, and alopecia). ORR was 6% (five of 83) for glembatumumab vedotin versus 7% (three of 41) for IC, without significant intertreatment differences for predefined strata. Secondary end point revealed ORR of 12% (10 of 83) versus 12% (five of 41) overall, and 30% (seven of 23) versus 9% (one of 11) for gpNMB overexpression (≥ 25% of tumor cells). Unplanned analysis showed ORR of 18% (five of 28) versus 0% (0 of 11) in patients with triple-negative breast cancer (TNBC), and 40% (four of 10) versus 0% (zero of six) in gpNMB-overexpressing TNBC.
CONCLUSION: Glembatumumab vedotin is well tolerated in heavily pretreated patients with breast cancer. Although the primary end point in advanced gpNMB-expressing breast cancer was not met for all enrolled patients (median tumor gpNMB expression, 5%), activity may be enhanced in patients with gpNMB-overexpressing tumors and/or TNBC. A pivotal phase II trial (METRIC [Metastatic Triple-Negative Breast Cancer]) is underway.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2015 |
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| Erschienen: |
2015 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:33 |
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| Enthalten in: |
Journal of clinical oncology : official journal of the American Society of Clinical Oncology - 33(2015), 14 vom: 10. Mai, Seite 1609-19 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Yardley, Denise A [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 20.07.2015 Date Revised 16.11.2017 published: Print-Electronic ClinicalTrials.gov: NCT01156753 Citation Status MEDLINE |
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| doi: |
10.1200/JCO.2014.56.2959 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM247799564 |
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| 041 | |a eng | ||
| 100 | 1 | |a Yardley, Denise A |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a EMERGE |b A Randomized Phase II Study of the Antibody-Drug Conjugate Glembatumumab Vedotin in Advanced Glycoprotein NMB-Expressing Breast Cancer |
| 264 | 1 | |c 2015 | |
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a ƒaComputermedien |b c |2 rdamedia | ||
| 338 | |a ƒa Online-Ressource |b cr |2 rdacarrier | ||
| 500 | |a Date Completed 20.07.2015 | ||
| 500 | |a Date Revised 16.11.2017 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a ClinicalTrials.gov: NCT01156753 | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a © 2015 by American Society of Clinical Oncology. | ||
| 520 | |a PURPOSE: Glycoprotein NMB (gpNMB), a negative prognostic marker, is overexpressed in multiple tumor types. Glembatumumab vedotin is a gpNMB-specific monoclonal antibody conjugated to the potent cytotoxin monomethyl auristatin E. This phase II study investigated the activity of glembatumumab vedotin in advanced breast cancer by gpNMB expression | ||
| 520 | |a PATIENTS AND METHODS: Patients (n = 124) with refractory breast cancer that expressed gpNMB in ≥ 5% of epithelial or stromal cells by central immunohistochemistry were stratified by gpNMB expression (tumor, low stromal intensity, high stromal intensity) and were randomly assigned 2:1 to glembatumumab vedotin (n = 83) or investigator's choice (IC) chemotherapy (n = 41). The study was powered to detect overall objective response rate (ORR) in the glembatumumab vedotin arm between 10% (null) and 22.5% (alternative hypothesis) with preplanned investigation of activity by gpNMB distribution and/or intensity (Stratum 1 to Stratum 3) | ||
| 520 | |a RESULTS: Glembatumumab vedotin was well tolerated as compared with IC chemotherapy (less hematologic toxicity; more rash, pruritus, neuropathy, and alopecia). ORR was 6% (five of 83) for glembatumumab vedotin versus 7% (three of 41) for IC, without significant intertreatment differences for predefined strata. Secondary end point revealed ORR of 12% (10 of 83) versus 12% (five of 41) overall, and 30% (seven of 23) versus 9% (one of 11) for gpNMB overexpression (≥ 25% of tumor cells). Unplanned analysis showed ORR of 18% (five of 28) versus 0% (0 of 11) in patients with triple-negative breast cancer (TNBC), and 40% (four of 10) versus 0% (zero of six) in gpNMB-overexpressing TNBC | ||
| 520 | |a CONCLUSION: Glembatumumab vedotin is well tolerated in heavily pretreated patients with breast cancer. Although the primary end point in advanced gpNMB-expressing breast cancer was not met for all enrolled patients (median tumor gpNMB expression, 5%), activity may be enhanced in patients with gpNMB-overexpressing tumors and/or TNBC. A pivotal phase II trial (METRIC [Metastatic Triple-Negative Breast Cancer]) is underway | ||
| 650 | 4 | |a Clinical Trial, Phase II | |
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Randomized Controlled Trial | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 7 | |a Antibodies, Monoclonal |2 NLM | |
| 650 | 7 | |a Antineoplastic Agents |2 NLM | |
| 650 | 7 | |a Biomarkers, Tumor |2 NLM | |
| 650 | 7 | |a GPNMB protein, human |2 NLM | |
| 650 | 7 | |a Immunoconjugates |2 NLM | |
| 650 | 7 | |a Membrane Glycoproteins |2 NLM | |
| 650 | 7 | |a glembatumumab vedotin |2 NLM | |
| 650 | 7 | |a 1568H6A58U |2 NLM | |
| 700 | 1 | |a Weaver, Robert |e verfasserin |4 aut | |
| 700 | 1 | |a Melisko, Michelle E |e verfasserin |4 aut | |
| 700 | 1 | |a Saleh, Mansoor N |e verfasserin |4 aut | |
| 700 | 1 | |a Arena, Francis P |e verfasserin |4 aut | |
| 700 | 1 | |a Forero, Andres |e verfasserin |4 aut | |
| 700 | 1 | |a Cigler, Tessa |e verfasserin |4 aut | |
| 700 | 1 | |a Stopeck, Alison |e verfasserin |4 aut | |
| 700 | 1 | |a Citrin, Dennis |e verfasserin |4 aut | |
| 700 | 1 | |a Oliff, Ira |e verfasserin |4 aut | |
| 700 | 1 | |a Bechhold, Rebecca |e verfasserin |4 aut | |
| 700 | 1 | |a Loutfi, Randa |e verfasserin |4 aut | |
| 700 | 1 | |a Garcia, Agustin A |e verfasserin |4 aut | |
| 700 | 1 | |a Cruickshank, Scott |e verfasserin |4 aut | |
| 700 | 1 | |a Crowley, Elizabeth |e verfasserin |4 aut | |
| 700 | 1 | |a Green, Jennifer |e verfasserin |4 aut | |
| 700 | 1 | |a Hawthorne, Thomas |e verfasserin |4 aut | |
| 700 | 1 | |a Yellin, Michael J |e verfasserin |4 aut | |
| 700 | 1 | |a Davis, Thomas A |e verfasserin |4 aut | |
| 700 | 1 | |a Vahdat, Linda T |e verfasserin |4 aut | |
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