A phase 1/2 trial of ibrutinib in combination with pembrolizumab in patients with mismatch repair proficient metastatic colorectal cancer
BACKGROUND: MMR proficient (pMMR) colorectal cancer (CRC) is usually unresponsive to immunotherapy. Recent data suggest that ibrutinib may enhance the anti-tumour activity of anti-PD-1 immunotherapy. In this study, we evaluated the safety and efficacy of ibrutinib plus pembrolizumab in refractory metastatic CRC.
METHODS: This was a phase 1/2 study in patients with refractory metastatic pMMR CRC. The primary endpoints for phases 1 and 2 were maximum tolerated dose (MTD) and disease control rate, respectively. The secondary endpoints were safety, progression-free survival (PFS) and overall survival (OS).
RESULTS: A total of 40 patients were enrolled. No dose-limiting toxicity was observed, and MTD was not identified. The highest tested dose of ibrutinib, 560 mg once daily, was combined with a fixed dose of pembrolizumab 200 mg every 3 weeks for the phase 2 portion. The most common grade 3/4 treatment-related adverse events were anaemia (21%), fatigue (8%) and elevated alkaline phosphatase (8%). Among 31 evaluable patients, 8 (26%) achieved stable disease, and no objective response was observed. The median PFS and OS were 1.4 and 6.6 months, respectively.
CONCLUSION: Ibrutinib 560 mg daily plus pembrolizumab 200 mg every 3 weeks appears to be well tolerated with limited anti-cancer activity in metastatic CRC. CLINICALTRIALS.
GOV IDENTIFIER: NCT03332498.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2021 |
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| Erschienen: |
2021 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:124 |
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| Enthalten in: |
British journal of cancer - 124(2021), 11 vom: 07. Mai, Seite 1803-1808 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Kim, Dae Won [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 15.12.2021 Date Revised 08.04.2022 published: Print-Electronic ClinicalTrials.gov: NCT03332498 Citation Status MEDLINE |
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| doi: |
10.1038/s41416-021-01368-z |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM323835295 |
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| 100 | 1 | |a Kim, Dae Won |e verfasserin |4 aut | |
| 245 | 1 | 2 | |a A phase 1/2 trial of ibrutinib in combination with pembrolizumab in patients with mismatch repair proficient metastatic colorectal cancer |
| 264 | 1 | |c 2021 | |
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| 500 | |a Date Completed 15.12.2021 | ||
| 500 | |a Date Revised 08.04.2022 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a ClinicalTrials.gov: NCT03332498 | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a BACKGROUND: MMR proficient (pMMR) colorectal cancer (CRC) is usually unresponsive to immunotherapy. Recent data suggest that ibrutinib may enhance the anti-tumour activity of anti-PD-1 immunotherapy. In this study, we evaluated the safety and efficacy of ibrutinib plus pembrolizumab in refractory metastatic CRC | ||
| 520 | |a METHODS: This was a phase 1/2 study in patients with refractory metastatic pMMR CRC. The primary endpoints for phases 1 and 2 were maximum tolerated dose (MTD) and disease control rate, respectively. The secondary endpoints were safety, progression-free survival (PFS) and overall survival (OS) | ||
| 520 | |a RESULTS: A total of 40 patients were enrolled. No dose-limiting toxicity was observed, and MTD was not identified. The highest tested dose of ibrutinib, 560 mg once daily, was combined with a fixed dose of pembrolizumab 200 mg every 3 weeks for the phase 2 portion. The most common grade 3/4 treatment-related adverse events were anaemia (21%), fatigue (8%) and elevated alkaline phosphatase (8%). Among 31 evaluable patients, 8 (26%) achieved stable disease, and no objective response was observed. The median PFS and OS were 1.4 and 6.6 months, respectively | ||
| 520 | |a CONCLUSION: Ibrutinib 560 mg daily plus pembrolizumab 200 mg every 3 weeks appears to be well tolerated with limited anti-cancer activity in metastatic CRC. CLINICALTRIALS | ||
| 520 | |a GOV IDENTIFIER: NCT03332498 | ||
| 650 | 4 | |a Clinical Trial, Phase I | |
| 650 | 4 | |a Clinical Trial, Phase II | |
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 7 | |a Antibodies, Monoclonal, Humanized |2 NLM | |
| 650 | 7 | |a Piperidines |2 NLM | |
| 650 | 7 | |a ibrutinib |2 NLM | |
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| 700 | 1 | |a Tan, Elaine |e verfasserin |4 aut | |
| 700 | 1 | |a Zhou, Jun-Min |e verfasserin |4 aut | |
| 700 | 1 | |a Schell, Michael J |e verfasserin |4 aut | |
| 700 | 1 | |a Martinez, Maria |e verfasserin |4 aut | |
| 700 | 1 | |a Yu, James |e verfasserin |4 aut | |
| 700 | 1 | |a Carballido, Estrella |e verfasserin |4 aut | |
| 700 | 1 | |a Mehta, Rutika |e verfasserin |4 aut | |
| 700 | 1 | |a Strosberg, Jonathan |e verfasserin |4 aut | |
| 700 | 1 | |a Imanirad, Iman |e verfasserin |4 aut | |
| 700 | 1 | |a Kim, Richard D |e verfasserin |4 aut | |
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