A phase I/II study of MCS110 with BRAF/MEK inhibition in patients with melanoma after progression on BRAF/MEK inhibition
Abstract Background: Prognosis for patients with metastatic melanoma has been improved dramatically with the development of BRAF/MEK directed therapy and immune checkpoint inhibition. However, resistance to therapy remains a challenge, particularly with BRAF/MEK targeted therapy which often has a li...
Ausführliche Beschreibung
Gespeichert in:
| Autor*in: |
Buchbinder, Elizabeth I. [verfasserIn] |
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| Format: |
E-Artikel |
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| Sprache: |
Englisch |
| Erschienen: |
2023 |
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| Schlagwörter: |
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| Anmerkung: |
© The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature 2023. Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law. |
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| Übergeordnetes Werk: |
Enthalten in: Investigational new drugs - Dordrecht [u.a.] : Springer Science + Business Media B.V, 1983, 41(2023), 3 vom: 25. Apr., Seite 365-370 |
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| Übergeordnetes Werk: |
volume:41 ; year:2023 ; number:3 ; day:25 ; month:04 ; pages:365-370 |
| Links: |
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| DOI / URN: |
10.1007/s10637-023-01364-5 |
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SPR052009181 |
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| 100 | 1 | |a Buchbinder, Elizabeth I. |e verfasserin |4 aut | |
| 245 | 1 | 2 | |a A phase I/II study of MCS110 with BRAF/MEK inhibition in patients with melanoma after progression on BRAF/MEK inhibition |
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| 520 | |a Abstract Background: Prognosis for patients with metastatic melanoma has been improved dramatically with the development of BRAF/MEK directed therapy and immune checkpoint inhibition. However, resistance to therapy remains a challenge, particularly with BRAF/MEK targeted therapy which often has a limited duration of efficacy. Pre-clinical data suggest that adding CSF1 inhibition to BRAF/MEK targeted therapy may reduce resistance and increase efficacy. Methods: We performed a phase I/II study to determine the safety and efficacy of CSF1 inhibition with MCS110 in combination with BRAF/MEK inhibition with dabrafenib/trametinib in patients with BRAF V600E/K mutant metastatic melanoma. The trial was terminated early due to a decision by the study sponsor to cease further development of MCS110. Results: Between September 2018 to July 2019 six patients were enrolled on the study. Patients were evenly split between female (50%) and male (50%) with a median age of 59.5 yrs. (26–71). Five patients experienced grade 3 toxicities that were possibly related to one of the therapies, there were no grade 4 or grade 5 events. One patient had a partial response (PR) by RECIST 1.1, one patient had stable disease (SD), 3 patients had disease progression (PD). Median progression free survival was 2.3 months (90% CI: 1.3 mos to not reached). Conclusion: MCS110 in combination with dabrafenib and trametinib was reasonably well tolerated in a small melanoma population. One response was observed in this small sample of patients suggesting this combination might be worthy of further exploration. | ||
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| 700 | 1 | |a Giobbie-Hurder, Anita |4 aut | |
| 700 | 1 | |a Ott, Patrick A. |4 aut | |
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10.1007/s10637-023-01364-5 doi (DE-627)SPR052009181 (SPR)s10637-023-01364-5-e DE-627 ger DE-627 rakwb eng Buchbinder, Elizabeth I. verfasserin aut A phase I/II study of MCS110 with BRAF/MEK inhibition in patients with melanoma after progression on BRAF/MEK inhibition 2023 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature 2023. Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law. Abstract Background: Prognosis for patients with metastatic melanoma has been improved dramatically with the development of BRAF/MEK directed therapy and immune checkpoint inhibition. However, resistance to therapy remains a challenge, particularly with BRAF/MEK targeted therapy which often has a limited duration of efficacy. Pre-clinical data suggest that adding CSF1 inhibition to BRAF/MEK targeted therapy may reduce resistance and increase efficacy. Methods: We performed a phase I/II study to determine the safety and efficacy of CSF1 inhibition with MCS110 in combination with BRAF/MEK inhibition with dabrafenib/trametinib in patients with BRAF V600E/K mutant metastatic melanoma. The trial was terminated early due to a decision by the study sponsor to cease further development of MCS110. Results: Between September 2018 to July 2019 six patients were enrolled on the study. Patients were evenly split between female (50%) and male (50%) with a median age of 59.5 yrs. (26–71). Five patients experienced grade 3 toxicities that were possibly related to one of the therapies, there were no grade 4 or grade 5 events. One patient had a partial response (PR) by RECIST 1.1, one patient had stable disease (SD), 3 patients had disease progression (PD). Median progression free survival was 2.3 months (90% CI: 1.3 mos to not reached). Conclusion: MCS110 in combination with dabrafenib and trametinib was reasonably well tolerated in a small melanoma population. One response was observed in this small sample of patients suggesting this combination might be worthy of further exploration. Melanoma (dpeaa)DE-He213 CSF1R inhibition (dpeaa)DE-He213 BRAF inhibition (dpeaa)DE-He213 MEK inhibition (dpeaa)DE-He213 Giobbie-Hurder, Anita aut Ott, Patrick A. aut Enthalten in Investigational new drugs Dordrecht [u.a.] : Springer Science + Business Media B.V, 1983 41(2023), 3 vom: 25. Apr., Seite 365-370 (DE-627)320481492 (DE-600)2009846-7 1573-0646 nnns volume:41 year:2023 number:3 day:25 month:04 pages:365-370 https://dx.doi.org/10.1007/s10637-023-01364-5 lizenzpflichtig Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_32 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_90 GBV_ILN_95 GBV_ILN_100 GBV_ILN_101 GBV_ILN_105 GBV_ILN_110 GBV_ILN_120 GBV_ILN_138 GBV_ILN_150 GBV_ILN_151 GBV_ILN_152 GBV_ILN_161 GBV_ILN_170 GBV_ILN_171 GBV_ILN_187 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_250 GBV_ILN_281 GBV_ILN_285 GBV_ILN_293 GBV_ILN_370 GBV_ILN_602 GBV_ILN_636 GBV_ILN_702 GBV_ILN_711 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2007 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2031 GBV_ILN_2034 GBV_ILN_2037 GBV_ILN_2038 GBV_ILN_2039 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2057 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2065 GBV_ILN_2068 GBV_ILN_2088 GBV_ILN_2093 GBV_ILN_2106 GBV_ILN_2107 GBV_ILN_2108 GBV_ILN_2110 GBV_ILN_2111 GBV_ILN_2112 GBV_ILN_2113 GBV_ILN_2118 GBV_ILN_2122 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2144 GBV_ILN_2147 GBV_ILN_2148 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2188 GBV_ILN_2190 GBV_ILN_2232 GBV_ILN_2336 GBV_ILN_2446 GBV_ILN_2470 GBV_ILN_2472 GBV_ILN_2507 GBV_ILN_2522 GBV_ILN_2548 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4046 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4242 GBV_ILN_4246 GBV_ILN_4249 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4326 GBV_ILN_4328 GBV_ILN_4333 GBV_ILN_4334 GBV_ILN_4335 GBV_ILN_4336 GBV_ILN_4338 GBV_ILN_4393 GBV_ILN_4700 AR 41 2023 3 25 04 365-370 |
| spelling |
10.1007/s10637-023-01364-5 doi (DE-627)SPR052009181 (SPR)s10637-023-01364-5-e DE-627 ger DE-627 rakwb eng Buchbinder, Elizabeth I. verfasserin aut A phase I/II study of MCS110 with BRAF/MEK inhibition in patients with melanoma after progression on BRAF/MEK inhibition 2023 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature 2023. Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law. Abstract Background: Prognosis for patients with metastatic melanoma has been improved dramatically with the development of BRAF/MEK directed therapy and immune checkpoint inhibition. However, resistance to therapy remains a challenge, particularly with BRAF/MEK targeted therapy which often has a limited duration of efficacy. Pre-clinical data suggest that adding CSF1 inhibition to BRAF/MEK targeted therapy may reduce resistance and increase efficacy. Methods: We performed a phase I/II study to determine the safety and efficacy of CSF1 inhibition with MCS110 in combination with BRAF/MEK inhibition with dabrafenib/trametinib in patients with BRAF V600E/K mutant metastatic melanoma. The trial was terminated early due to a decision by the study sponsor to cease further development of MCS110. Results: Between September 2018 to July 2019 six patients were enrolled on the study. Patients were evenly split between female (50%) and male (50%) with a median age of 59.5 yrs. (26–71). Five patients experienced grade 3 toxicities that were possibly related to one of the therapies, there were no grade 4 or grade 5 events. One patient had a partial response (PR) by RECIST 1.1, one patient had stable disease (SD), 3 patients had disease progression (PD). Median progression free survival was 2.3 months (90% CI: 1.3 mos to not reached). Conclusion: MCS110 in combination with dabrafenib and trametinib was reasonably well tolerated in a small melanoma population. One response was observed in this small sample of patients suggesting this combination might be worthy of further exploration. Melanoma (dpeaa)DE-He213 CSF1R inhibition (dpeaa)DE-He213 BRAF inhibition (dpeaa)DE-He213 MEK inhibition (dpeaa)DE-He213 Giobbie-Hurder, Anita aut Ott, Patrick A. aut Enthalten in Investigational new drugs Dordrecht [u.a.] : Springer Science + Business Media B.V, 1983 41(2023), 3 vom: 25. Apr., Seite 365-370 (DE-627)320481492 (DE-600)2009846-7 1573-0646 nnns volume:41 year:2023 number:3 day:25 month:04 pages:365-370 https://dx.doi.org/10.1007/s10637-023-01364-5 lizenzpflichtig Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_32 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_90 GBV_ILN_95 GBV_ILN_100 GBV_ILN_101 GBV_ILN_105 GBV_ILN_110 GBV_ILN_120 GBV_ILN_138 GBV_ILN_150 GBV_ILN_151 GBV_ILN_152 GBV_ILN_161 GBV_ILN_170 GBV_ILN_171 GBV_ILN_187 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_250 GBV_ILN_281 GBV_ILN_285 GBV_ILN_293 GBV_ILN_370 GBV_ILN_602 GBV_ILN_636 GBV_ILN_702 GBV_ILN_711 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2007 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2031 GBV_ILN_2034 GBV_ILN_2037 GBV_ILN_2038 GBV_ILN_2039 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2057 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2065 GBV_ILN_2068 GBV_ILN_2088 GBV_ILN_2093 GBV_ILN_2106 GBV_ILN_2107 GBV_ILN_2108 GBV_ILN_2110 GBV_ILN_2111 GBV_ILN_2112 GBV_ILN_2113 GBV_ILN_2118 GBV_ILN_2122 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2144 GBV_ILN_2147 GBV_ILN_2148 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2188 GBV_ILN_2190 GBV_ILN_2232 GBV_ILN_2336 GBV_ILN_2446 GBV_ILN_2470 GBV_ILN_2472 GBV_ILN_2507 GBV_ILN_2522 GBV_ILN_2548 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4046 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4242 GBV_ILN_4246 GBV_ILN_4249 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4326 GBV_ILN_4328 GBV_ILN_4333 GBV_ILN_4334 GBV_ILN_4335 GBV_ILN_4336 GBV_ILN_4338 GBV_ILN_4393 GBV_ILN_4700 AR 41 2023 3 25 04 365-370 |
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10.1007/s10637-023-01364-5 doi (DE-627)SPR052009181 (SPR)s10637-023-01364-5-e DE-627 ger DE-627 rakwb eng Buchbinder, Elizabeth I. verfasserin aut A phase I/II study of MCS110 with BRAF/MEK inhibition in patients with melanoma after progression on BRAF/MEK inhibition 2023 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature 2023. Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law. Abstract Background: Prognosis for patients with metastatic melanoma has been improved dramatically with the development of BRAF/MEK directed therapy and immune checkpoint inhibition. However, resistance to therapy remains a challenge, particularly with BRAF/MEK targeted therapy which often has a limited duration of efficacy. Pre-clinical data suggest that adding CSF1 inhibition to BRAF/MEK targeted therapy may reduce resistance and increase efficacy. Methods: We performed a phase I/II study to determine the safety and efficacy of CSF1 inhibition with MCS110 in combination with BRAF/MEK inhibition with dabrafenib/trametinib in patients with BRAF V600E/K mutant metastatic melanoma. The trial was terminated early due to a decision by the study sponsor to cease further development of MCS110. Results: Between September 2018 to July 2019 six patients were enrolled on the study. Patients were evenly split between female (50%) and male (50%) with a median age of 59.5 yrs. (26–71). Five patients experienced grade 3 toxicities that were possibly related to one of the therapies, there were no grade 4 or grade 5 events. One patient had a partial response (PR) by RECIST 1.1, one patient had stable disease (SD), 3 patients had disease progression (PD). Median progression free survival was 2.3 months (90% CI: 1.3 mos to not reached). Conclusion: MCS110 in combination with dabrafenib and trametinib was reasonably well tolerated in a small melanoma population. One response was observed in this small sample of patients suggesting this combination might be worthy of further exploration. Melanoma (dpeaa)DE-He213 CSF1R inhibition (dpeaa)DE-He213 BRAF inhibition (dpeaa)DE-He213 MEK inhibition (dpeaa)DE-He213 Giobbie-Hurder, Anita aut Ott, Patrick A. aut Enthalten in Investigational new drugs Dordrecht [u.a.] : Springer Science + Business Media B.V, 1983 41(2023), 3 vom: 25. Apr., Seite 365-370 (DE-627)320481492 (DE-600)2009846-7 1573-0646 nnns volume:41 year:2023 number:3 day:25 month:04 pages:365-370 https://dx.doi.org/10.1007/s10637-023-01364-5 lizenzpflichtig Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_32 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_90 GBV_ILN_95 GBV_ILN_100 GBV_ILN_101 GBV_ILN_105 GBV_ILN_110 GBV_ILN_120 GBV_ILN_138 GBV_ILN_150 GBV_ILN_151 GBV_ILN_152 GBV_ILN_161 GBV_ILN_170 GBV_ILN_171 GBV_ILN_187 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_250 GBV_ILN_281 GBV_ILN_285 GBV_ILN_293 GBV_ILN_370 GBV_ILN_602 GBV_ILN_636 GBV_ILN_702 GBV_ILN_711 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2007 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2031 GBV_ILN_2034 GBV_ILN_2037 GBV_ILN_2038 GBV_ILN_2039 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2057 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2065 GBV_ILN_2068 GBV_ILN_2088 GBV_ILN_2093 GBV_ILN_2106 GBV_ILN_2107 GBV_ILN_2108 GBV_ILN_2110 GBV_ILN_2111 GBV_ILN_2112 GBV_ILN_2113 GBV_ILN_2118 GBV_ILN_2122 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2144 GBV_ILN_2147 GBV_ILN_2148 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2188 GBV_ILN_2190 GBV_ILN_2232 GBV_ILN_2336 GBV_ILN_2446 GBV_ILN_2470 GBV_ILN_2472 GBV_ILN_2507 GBV_ILN_2522 GBV_ILN_2548 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4046 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4242 GBV_ILN_4246 GBV_ILN_4249 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4326 GBV_ILN_4328 GBV_ILN_4333 GBV_ILN_4334 GBV_ILN_4335 GBV_ILN_4336 GBV_ILN_4338 GBV_ILN_4393 GBV_ILN_4700 AR 41 2023 3 25 04 365-370 |
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10.1007/s10637-023-01364-5 doi (DE-627)SPR052009181 (SPR)s10637-023-01364-5-e DE-627 ger DE-627 rakwb eng Buchbinder, Elizabeth I. verfasserin aut A phase I/II study of MCS110 with BRAF/MEK inhibition in patients with melanoma after progression on BRAF/MEK inhibition 2023 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature 2023. Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law. Abstract Background: Prognosis for patients with metastatic melanoma has been improved dramatically with the development of BRAF/MEK directed therapy and immune checkpoint inhibition. However, resistance to therapy remains a challenge, particularly with BRAF/MEK targeted therapy which often has a limited duration of efficacy. Pre-clinical data suggest that adding CSF1 inhibition to BRAF/MEK targeted therapy may reduce resistance and increase efficacy. Methods: We performed a phase I/II study to determine the safety and efficacy of CSF1 inhibition with MCS110 in combination with BRAF/MEK inhibition with dabrafenib/trametinib in patients with BRAF V600E/K mutant metastatic melanoma. The trial was terminated early due to a decision by the study sponsor to cease further development of MCS110. Results: Between September 2018 to July 2019 six patients were enrolled on the study. Patients were evenly split between female (50%) and male (50%) with a median age of 59.5 yrs. (26–71). Five patients experienced grade 3 toxicities that were possibly related to one of the therapies, there were no grade 4 or grade 5 events. One patient had a partial response (PR) by RECIST 1.1, one patient had stable disease (SD), 3 patients had disease progression (PD). Median progression free survival was 2.3 months (90% CI: 1.3 mos to not reached). Conclusion: MCS110 in combination with dabrafenib and trametinib was reasonably well tolerated in a small melanoma population. One response was observed in this small sample of patients suggesting this combination might be worthy of further exploration. Melanoma (dpeaa)DE-He213 CSF1R inhibition (dpeaa)DE-He213 BRAF inhibition (dpeaa)DE-He213 MEK inhibition (dpeaa)DE-He213 Giobbie-Hurder, Anita aut Ott, Patrick A. aut Enthalten in Investigational new drugs Dordrecht [u.a.] : Springer Science + Business Media B.V, 1983 41(2023), 3 vom: 25. Apr., Seite 365-370 (DE-627)320481492 (DE-600)2009846-7 1573-0646 nnns volume:41 year:2023 number:3 day:25 month:04 pages:365-370 https://dx.doi.org/10.1007/s10637-023-01364-5 lizenzpflichtig Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_32 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_90 GBV_ILN_95 GBV_ILN_100 GBV_ILN_101 GBV_ILN_105 GBV_ILN_110 GBV_ILN_120 GBV_ILN_138 GBV_ILN_150 GBV_ILN_151 GBV_ILN_152 GBV_ILN_161 GBV_ILN_170 GBV_ILN_171 GBV_ILN_187 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_250 GBV_ILN_281 GBV_ILN_285 GBV_ILN_293 GBV_ILN_370 GBV_ILN_602 GBV_ILN_636 GBV_ILN_702 GBV_ILN_711 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2007 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2031 GBV_ILN_2034 GBV_ILN_2037 GBV_ILN_2038 GBV_ILN_2039 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2057 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2065 GBV_ILN_2068 GBV_ILN_2088 GBV_ILN_2093 GBV_ILN_2106 GBV_ILN_2107 GBV_ILN_2108 GBV_ILN_2110 GBV_ILN_2111 GBV_ILN_2112 GBV_ILN_2113 GBV_ILN_2118 GBV_ILN_2122 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2144 GBV_ILN_2147 GBV_ILN_2148 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2188 GBV_ILN_2190 GBV_ILN_2232 GBV_ILN_2336 GBV_ILN_2446 GBV_ILN_2470 GBV_ILN_2472 GBV_ILN_2507 GBV_ILN_2522 GBV_ILN_2548 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4046 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4242 GBV_ILN_4246 GBV_ILN_4249 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4326 GBV_ILN_4328 GBV_ILN_4333 GBV_ILN_4334 GBV_ILN_4335 GBV_ILN_4336 GBV_ILN_4338 GBV_ILN_4393 GBV_ILN_4700 AR 41 2023 3 25 04 365-370 |
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10.1007/s10637-023-01364-5 doi (DE-627)SPR052009181 (SPR)s10637-023-01364-5-e DE-627 ger DE-627 rakwb eng Buchbinder, Elizabeth I. verfasserin aut A phase I/II study of MCS110 with BRAF/MEK inhibition in patients with melanoma after progression on BRAF/MEK inhibition 2023 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature 2023. Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law. Abstract Background: Prognosis for patients with metastatic melanoma has been improved dramatically with the development of BRAF/MEK directed therapy and immune checkpoint inhibition. However, resistance to therapy remains a challenge, particularly with BRAF/MEK targeted therapy which often has a limited duration of efficacy. Pre-clinical data suggest that adding CSF1 inhibition to BRAF/MEK targeted therapy may reduce resistance and increase efficacy. Methods: We performed a phase I/II study to determine the safety and efficacy of CSF1 inhibition with MCS110 in combination with BRAF/MEK inhibition with dabrafenib/trametinib in patients with BRAF V600E/K mutant metastatic melanoma. The trial was terminated early due to a decision by the study sponsor to cease further development of MCS110. Results: Between September 2018 to July 2019 six patients were enrolled on the study. Patients were evenly split between female (50%) and male (50%) with a median age of 59.5 yrs. (26–71). Five patients experienced grade 3 toxicities that were possibly related to one of the therapies, there were no grade 4 or grade 5 events. One patient had a partial response (PR) by RECIST 1.1, one patient had stable disease (SD), 3 patients had disease progression (PD). Median progression free survival was 2.3 months (90% CI: 1.3 mos to not reached). Conclusion: MCS110 in combination with dabrafenib and trametinib was reasonably well tolerated in a small melanoma population. One response was observed in this small sample of patients suggesting this combination might be worthy of further exploration. Melanoma (dpeaa)DE-He213 CSF1R inhibition (dpeaa)DE-He213 BRAF inhibition (dpeaa)DE-He213 MEK inhibition (dpeaa)DE-He213 Giobbie-Hurder, Anita aut Ott, Patrick A. aut Enthalten in Investigational new drugs Dordrecht [u.a.] : Springer Science + Business Media B.V, 1983 41(2023), 3 vom: 25. Apr., Seite 365-370 (DE-627)320481492 (DE-600)2009846-7 1573-0646 nnns volume:41 year:2023 number:3 day:25 month:04 pages:365-370 https://dx.doi.org/10.1007/s10637-023-01364-5 lizenzpflichtig Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_32 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_90 GBV_ILN_95 GBV_ILN_100 GBV_ILN_101 GBV_ILN_105 GBV_ILN_110 GBV_ILN_120 GBV_ILN_138 GBV_ILN_150 GBV_ILN_151 GBV_ILN_152 GBV_ILN_161 GBV_ILN_170 GBV_ILN_171 GBV_ILN_187 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_250 GBV_ILN_281 GBV_ILN_285 GBV_ILN_293 GBV_ILN_370 GBV_ILN_602 GBV_ILN_636 GBV_ILN_702 GBV_ILN_711 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2007 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2031 GBV_ILN_2034 GBV_ILN_2037 GBV_ILN_2038 GBV_ILN_2039 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2057 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2065 GBV_ILN_2068 GBV_ILN_2088 GBV_ILN_2093 GBV_ILN_2106 GBV_ILN_2107 GBV_ILN_2108 GBV_ILN_2110 GBV_ILN_2111 GBV_ILN_2112 GBV_ILN_2113 GBV_ILN_2118 GBV_ILN_2122 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2144 GBV_ILN_2147 GBV_ILN_2148 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2188 GBV_ILN_2190 GBV_ILN_2232 GBV_ILN_2336 GBV_ILN_2446 GBV_ILN_2470 GBV_ILN_2472 GBV_ILN_2507 GBV_ILN_2522 GBV_ILN_2548 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4046 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4242 GBV_ILN_4246 GBV_ILN_4249 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4326 GBV_ILN_4328 GBV_ILN_4333 GBV_ILN_4334 GBV_ILN_4335 GBV_ILN_4336 GBV_ILN_4338 GBV_ILN_4393 GBV_ILN_4700 AR 41 2023 3 25 04 365-370 |
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Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.</subfield></datafield><datafield tag="520" ind1=" " ind2=" "><subfield code="a">Abstract Background: Prognosis for patients with metastatic melanoma has been improved dramatically with the development of BRAF/MEK directed therapy and immune checkpoint inhibition. However, resistance to therapy remains a challenge, particularly with BRAF/MEK targeted therapy which often has a limited duration of efficacy. Pre-clinical data suggest that adding CSF1 inhibition to BRAF/MEK targeted therapy may reduce resistance and increase efficacy. Methods: We performed a phase I/II study to determine the safety and efficacy of CSF1 inhibition with MCS110 in combination with BRAF/MEK inhibition with dabrafenib/trametinib in patients with BRAF V600E/K mutant metastatic melanoma. The trial was terminated early due to a decision by the study sponsor to cease further development of MCS110. Results: Between September 2018 to July 2019 six patients were enrolled on the study. Patients were evenly split between female (50%) and male (50%) with a median age of 59.5 yrs. (26–71). Five patients experienced grade 3 toxicities that were possibly related to one of the therapies, there were no grade 4 or grade 5 events. One patient had a partial response (PR) by RECIST 1.1, one patient had stable disease (SD), 3 patients had disease progression (PD). Median progression free survival was 2.3 months (90% CI: 1.3 mos to not reached). Conclusion: MCS110 in combination with dabrafenib and trametinib was reasonably well tolerated in a small melanoma population. 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Buchbinder, Elizabeth I. |
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Buchbinder, Elizabeth I. misc Melanoma misc CSF1R inhibition misc BRAF inhibition misc MEK inhibition A phase I/II study of MCS110 with BRAF/MEK inhibition in patients with melanoma after progression on BRAF/MEK inhibition |
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A phase I/II study of MCS110 with BRAF/MEK inhibition in patients with melanoma after progression on BRAF/MEK inhibition Melanoma (dpeaa)DE-He213 CSF1R inhibition (dpeaa)DE-He213 BRAF inhibition (dpeaa)DE-He213 MEK inhibition (dpeaa)DE-He213 |
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phase i/ii study of mcs110 with braf/mek inhibition in patients with melanoma after progression on braf/mek inhibition |
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A phase I/II study of MCS110 with BRAF/MEK inhibition in patients with melanoma after progression on BRAF/MEK inhibition |
| abstract |
Abstract Background: Prognosis for patients with metastatic melanoma has been improved dramatically with the development of BRAF/MEK directed therapy and immune checkpoint inhibition. However, resistance to therapy remains a challenge, particularly with BRAF/MEK targeted therapy which often has a limited duration of efficacy. Pre-clinical data suggest that adding CSF1 inhibition to BRAF/MEK targeted therapy may reduce resistance and increase efficacy. Methods: We performed a phase I/II study to determine the safety and efficacy of CSF1 inhibition with MCS110 in combination with BRAF/MEK inhibition with dabrafenib/trametinib in patients with BRAF V600E/K mutant metastatic melanoma. The trial was terminated early due to a decision by the study sponsor to cease further development of MCS110. Results: Between September 2018 to July 2019 six patients were enrolled on the study. Patients were evenly split between female (50%) and male (50%) with a median age of 59.5 yrs. (26–71). Five patients experienced grade 3 toxicities that were possibly related to one of the therapies, there were no grade 4 or grade 5 events. One patient had a partial response (PR) by RECIST 1.1, one patient had stable disease (SD), 3 patients had disease progression (PD). Median progression free survival was 2.3 months (90% CI: 1.3 mos to not reached). Conclusion: MCS110 in combination with dabrafenib and trametinib was reasonably well tolerated in a small melanoma population. One response was observed in this small sample of patients suggesting this combination might be worthy of further exploration. © The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature 2023. Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law. |
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Abstract Background: Prognosis for patients with metastatic melanoma has been improved dramatically with the development of BRAF/MEK directed therapy and immune checkpoint inhibition. However, resistance to therapy remains a challenge, particularly with BRAF/MEK targeted therapy which often has a limited duration of efficacy. Pre-clinical data suggest that adding CSF1 inhibition to BRAF/MEK targeted therapy may reduce resistance and increase efficacy. Methods: We performed a phase I/II study to determine the safety and efficacy of CSF1 inhibition with MCS110 in combination with BRAF/MEK inhibition with dabrafenib/trametinib in patients with BRAF V600E/K mutant metastatic melanoma. The trial was terminated early due to a decision by the study sponsor to cease further development of MCS110. Results: Between September 2018 to July 2019 six patients were enrolled on the study. Patients were evenly split between female (50%) and male (50%) with a median age of 59.5 yrs. (26–71). Five patients experienced grade 3 toxicities that were possibly related to one of the therapies, there were no grade 4 or grade 5 events. One patient had a partial response (PR) by RECIST 1.1, one patient had stable disease (SD), 3 patients had disease progression (PD). Median progression free survival was 2.3 months (90% CI: 1.3 mos to not reached). Conclusion: MCS110 in combination with dabrafenib and trametinib was reasonably well tolerated in a small melanoma population. One response was observed in this small sample of patients suggesting this combination might be worthy of further exploration. © The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature 2023. Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law. |
| abstract_unstemmed |
Abstract Background: Prognosis for patients with metastatic melanoma has been improved dramatically with the development of BRAF/MEK directed therapy and immune checkpoint inhibition. However, resistance to therapy remains a challenge, particularly with BRAF/MEK targeted therapy which often has a limited duration of efficacy. Pre-clinical data suggest that adding CSF1 inhibition to BRAF/MEK targeted therapy may reduce resistance and increase efficacy. Methods: We performed a phase I/II study to determine the safety and efficacy of CSF1 inhibition with MCS110 in combination with BRAF/MEK inhibition with dabrafenib/trametinib in patients with BRAF V600E/K mutant metastatic melanoma. The trial was terminated early due to a decision by the study sponsor to cease further development of MCS110. Results: Between September 2018 to July 2019 six patients were enrolled on the study. Patients were evenly split between female (50%) and male (50%) with a median age of 59.5 yrs. (26–71). Five patients experienced grade 3 toxicities that were possibly related to one of the therapies, there were no grade 4 or grade 5 events. One patient had a partial response (PR) by RECIST 1.1, one patient had stable disease (SD), 3 patients had disease progression (PD). Median progression free survival was 2.3 months (90% CI: 1.3 mos to not reached). Conclusion: MCS110 in combination with dabrafenib and trametinib was reasonably well tolerated in a small melanoma population. One response was observed in this small sample of patients suggesting this combination might be worthy of further exploration. © The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature 2023. Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law. |
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A phase I/II study of MCS110 with BRAF/MEK inhibition in patients with melanoma after progression on BRAF/MEK inhibition |
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Giobbie-Hurder, Anita Ott, Patrick A. |
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| score |
7.399106 |