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Ipilimumab, Pembrolizumab, or Nivolumab in Combination with BBI608 in Patients with Advanced Cancers Treated at MD Anderson Cancer Center
SIMPLE SUMMARY: BBI608 is an investigational reactive oxygen species generator that affects several molecular and oncogenic pathways, including the STAT3 pathway, and may overcome resistance to immune checkpoint inhibitors. We investigated BBI608 combined with immunotherapy (ipilimumab, pembrolizuma...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8909492/ https://www.ncbi.nlm.nih.gov/pubmed/35267638 http://dx.doi.org/10.3390/cancers14051330 |
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author | Vo, Henry Hiep Cartwright, Carrie Song, I-Wen Karp, Daniel D. Nogueras Gonzalez, Graciela M. Xie, Yuran Karol, Michael Hitron, Matthew Vining, David Tsimberidou, Apostolia-Maria |
author_facet | Vo, Henry Hiep Cartwright, Carrie Song, I-Wen Karp, Daniel D. Nogueras Gonzalez, Graciela M. Xie, Yuran Karol, Michael Hitron, Matthew Vining, David Tsimberidou, Apostolia-Maria |
author_sort | Vo, Henry Hiep |
collection | PubMed |
description | SIMPLE SUMMARY: BBI608 is an investigational reactive oxygen species generator that affects several molecular and oncogenic pathways, including the STAT3 pathway, and may overcome resistance to immune checkpoint inhibitors. We investigated BBI608 combined with immunotherapy (ipilimumab, pembrolizumab, or nivolumab) in patients with advanced cancer. Treatment was well tolerated overall. Only 2 of 12 patients had Grade 3 diarrhea. Five patients treated with BBI608/nivolumab had prolonged disease stabilization lasting for 12.1, 10.1, 8.0, 7.7 and 7.4 months. Four patients had prolonged overall survival (53.0, 48.7, 51.9 and 48.2 months). Prospective studies of BBI608 are warranted. ABSTRACT: Background: BBI608 is an investigational reactive oxygen species generator that affects several molecular pathways. We investigated BBI608 combined with immune checkpoint inhibitors in patients with advanced cancers. Methods: BBI608 (orally twice daily) was combined with ipilimumab (3 mg/kg IV every 3 weeks); pembrolizumab (2 mg/kg IV every 3 weeks); or nivolumab (3 mg/kg IV every 4 weeks). We assessed the safety, antitumor activity and the pharmacokinetic profile of BBI combined with immunotherapy. Results: From 1/2017 to 3/2017, 12 patients were treated (median age, 54 years; range, 31–78; 6 men). Treatment was overall well tolerated. No dose-limiting toxicity was observed. The most common adverse events were diarrhea (5 patients: grade (G)1–2, n = 3; G3, n = 2) and nausea (4 patients, all G1). Prolonged disease stabilization was noted in five patients treated with BBI608/nivolumab lasting for 12.1, 10.1, 8.0, 7.7 and 7.4 months. The median progression-free survival was 2.73 months. The median overall survival was 7.56 months. Four patients had prolonged overall survival (53.0, 48.7, 51.9 and 48.2 months). Conclusions: Checkpoint inhibitors combined with BBI608 were well tolerated. Several patients had prolonged disease stabilization and overall survival. Prospective studies to elucidate the mechanisms of response and resistance to BBI608 are warranted. |
format | Online Article Text |
id | pubmed-8909492 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-89094922022-03-11 Ipilimumab, Pembrolizumab, or Nivolumab in Combination with BBI608 in Patients with Advanced Cancers Treated at MD Anderson Cancer Center Vo, Henry Hiep Cartwright, Carrie Song, I-Wen Karp, Daniel D. Nogueras Gonzalez, Graciela M. Xie, Yuran Karol, Michael Hitron, Matthew Vining, David Tsimberidou, Apostolia-Maria Cancers (Basel) Article SIMPLE SUMMARY: BBI608 is an investigational reactive oxygen species generator that affects several molecular and oncogenic pathways, including the STAT3 pathway, and may overcome resistance to immune checkpoint inhibitors. We investigated BBI608 combined with immunotherapy (ipilimumab, pembrolizumab, or nivolumab) in patients with advanced cancer. Treatment was well tolerated overall. Only 2 of 12 patients had Grade 3 diarrhea. Five patients treated with BBI608/nivolumab had prolonged disease stabilization lasting for 12.1, 10.1, 8.0, 7.7 and 7.4 months. Four patients had prolonged overall survival (53.0, 48.7, 51.9 and 48.2 months). Prospective studies of BBI608 are warranted. ABSTRACT: Background: BBI608 is an investigational reactive oxygen species generator that affects several molecular pathways. We investigated BBI608 combined with immune checkpoint inhibitors in patients with advanced cancers. Methods: BBI608 (orally twice daily) was combined with ipilimumab (3 mg/kg IV every 3 weeks); pembrolizumab (2 mg/kg IV every 3 weeks); or nivolumab (3 mg/kg IV every 4 weeks). We assessed the safety, antitumor activity and the pharmacokinetic profile of BBI combined with immunotherapy. Results: From 1/2017 to 3/2017, 12 patients were treated (median age, 54 years; range, 31–78; 6 men). Treatment was overall well tolerated. No dose-limiting toxicity was observed. The most common adverse events were diarrhea (5 patients: grade (G)1–2, n = 3; G3, n = 2) and nausea (4 patients, all G1). Prolonged disease stabilization was noted in five patients treated with BBI608/nivolumab lasting for 12.1, 10.1, 8.0, 7.7 and 7.4 months. The median progression-free survival was 2.73 months. The median overall survival was 7.56 months. Four patients had prolonged overall survival (53.0, 48.7, 51.9 and 48.2 months). Conclusions: Checkpoint inhibitors combined with BBI608 were well tolerated. Several patients had prolonged disease stabilization and overall survival. Prospective studies to elucidate the mechanisms of response and resistance to BBI608 are warranted. MDPI 2022-03-04 /pmc/articles/PMC8909492/ /pubmed/35267638 http://dx.doi.org/10.3390/cancers14051330 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Vo, Henry Hiep Cartwright, Carrie Song, I-Wen Karp, Daniel D. Nogueras Gonzalez, Graciela M. Xie, Yuran Karol, Michael Hitron, Matthew Vining, David Tsimberidou, Apostolia-Maria Ipilimumab, Pembrolizumab, or Nivolumab in Combination with BBI608 in Patients with Advanced Cancers Treated at MD Anderson Cancer Center |
title | Ipilimumab, Pembrolizumab, or Nivolumab in Combination with BBI608 in Patients with Advanced Cancers Treated at MD Anderson Cancer Center |
title_full | Ipilimumab, Pembrolizumab, or Nivolumab in Combination with BBI608 in Patients with Advanced Cancers Treated at MD Anderson Cancer Center |
title_fullStr | Ipilimumab, Pembrolizumab, or Nivolumab in Combination with BBI608 in Patients with Advanced Cancers Treated at MD Anderson Cancer Center |
title_full_unstemmed | Ipilimumab, Pembrolizumab, or Nivolumab in Combination with BBI608 in Patients with Advanced Cancers Treated at MD Anderson Cancer Center |
title_short | Ipilimumab, Pembrolizumab, or Nivolumab in Combination with BBI608 in Patients with Advanced Cancers Treated at MD Anderson Cancer Center |
title_sort | ipilimumab, pembrolizumab, or nivolumab in combination with bbi608 in patients with advanced cancers treated at md anderson cancer center |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8909492/ https://www.ncbi.nlm.nih.gov/pubmed/35267638 http://dx.doi.org/10.3390/cancers14051330 |
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