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TIPS-04 A RANDOMIZED, MULTI-INSTITUTIONAL PILOT STUDY TO EVALUATE THE MOLECULAR AND CELLULAR RESPONSE TO TREATMENT WITH NIVOLUMAB WITH EITHER ADJUVANT IPILIMUMAB OR RELATLIMAB IN ADULT PATIENTS WITH SURGICALLY RESECTABLE MELANOMA BRAIN METASTASES: ONGOING TRIAL
BACKGROUND: Melanoma brain metastases (MBM) is a major cause of morbidity and mortality. The way melanoma malignant cells interact with the microenvironment in distal sites including the brain, plays a major role in tumorigenesis, metastasis, and tumor survival. Data supports the tumor microenvironm...
Autores principales: | , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Oxford University Press
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10402413/ http://dx.doi.org/10.1093/noajnl/vdad070.135 |
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author | Pina, Yolanda Chen, Ann Tran, Nam Etame, Arnold Liu, James Furlan, Andre Beer Mokhtari, Sepideh Peguero, Edwin Li, Jiannong Law, Vincent Khushalani, Nikhil Smalley, Inna Vogelbaum, Michael Yu, Michael Arrington, John Macaulay, Robert Tawbi, Hussein Smalley, Keiran Forsyth, Peter |
author_facet | Pina, Yolanda Chen, Ann Tran, Nam Etame, Arnold Liu, James Furlan, Andre Beer Mokhtari, Sepideh Peguero, Edwin Li, Jiannong Law, Vincent Khushalani, Nikhil Smalley, Inna Vogelbaum, Michael Yu, Michael Arrington, John Macaulay, Robert Tawbi, Hussein Smalley, Keiran Forsyth, Peter |
author_sort | Pina, Yolanda |
collection | PubMed |
description | BACKGROUND: Melanoma brain metastases (MBM) is a major cause of morbidity and mortality. The way melanoma malignant cells interact with the microenvironment in distal sites including the brain, plays a major role in tumorigenesis, metastasis, and tumor survival. Data supports the tumor microenvironment (TME) in MBM is different at the molecular/cellular level than the TME in other metastatic sites. Objectives: (1) to determine the safety and feasibility of presurgical administration of Nivolumab (Nivo) in combination with Ipilimumab (Ipi) or Opdualag (Nivo + Relatlimab [Rela]); and (2) to investigate the TME and estimate the immune cell population difference between the different treatment groups. METHODS: We are carrying a randomized open label pilot study with adult patients (n=24) with MBM with surgically resectable brain tumors, who have not received treatment with immune-checkpoint inhibitors for six months or with BRAF/MEK inhibitors for 1 month, and on ≤3 mg/day dexamethasone or equivalent/day. Patients will be treated with either Nivo+Ipi, Opdualag, or no treatment pre-surgery (NCT05704933). Following treatment, all subjects will undergo surgical resection of their brain tumors and systemic disease biopsy, if clinically indicated. Post-surgery, all subjects will receive stereotactic radiosurgery (SRS) or fractionated SRS (fSRS), followed by Nivo+Ipi x4 dosages and adjuvant Nivo for 1 year or until disease progression and/or intolerable adverse events. All subjects will be on levetiracetam 500 mg twice a day or equivalent medication throughout the duration of the study. A lumbar puncture for CSF collection will be performed if clinically indicated and CSF and blood collected at different time points. Collected tissue will be send for sc RNA-seq, TCR/BCR seq. A one-way ANOVA will be used to compare the cellular population differences between treatment arms. CNS clinical response will be defined using RANO-BM and i-RANO. Trial is open and actively recruiting. |
format | Online Article Text |
id | pubmed-10402413 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Oxford University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-104024132023-08-05 TIPS-04 A RANDOMIZED, MULTI-INSTITUTIONAL PILOT STUDY TO EVALUATE THE MOLECULAR AND CELLULAR RESPONSE TO TREATMENT WITH NIVOLUMAB WITH EITHER ADJUVANT IPILIMUMAB OR RELATLIMAB IN ADULT PATIENTS WITH SURGICALLY RESECTABLE MELANOMA BRAIN METASTASES: ONGOING TRIAL Pina, Yolanda Chen, Ann Tran, Nam Etame, Arnold Liu, James Furlan, Andre Beer Mokhtari, Sepideh Peguero, Edwin Li, Jiannong Law, Vincent Khushalani, Nikhil Smalley, Inna Vogelbaum, Michael Yu, Michael Arrington, John Macaulay, Robert Tawbi, Hussein Smalley, Keiran Forsyth, Peter Neurooncol Adv Final Category: Trials in Progress BACKGROUND: Melanoma brain metastases (MBM) is a major cause of morbidity and mortality. The way melanoma malignant cells interact with the microenvironment in distal sites including the brain, plays a major role in tumorigenesis, metastasis, and tumor survival. Data supports the tumor microenvironment (TME) in MBM is different at the molecular/cellular level than the TME in other metastatic sites. Objectives: (1) to determine the safety and feasibility of presurgical administration of Nivolumab (Nivo) in combination with Ipilimumab (Ipi) or Opdualag (Nivo + Relatlimab [Rela]); and (2) to investigate the TME and estimate the immune cell population difference between the different treatment groups. METHODS: We are carrying a randomized open label pilot study with adult patients (n=24) with MBM with surgically resectable brain tumors, who have not received treatment with immune-checkpoint inhibitors for six months or with BRAF/MEK inhibitors for 1 month, and on ≤3 mg/day dexamethasone or equivalent/day. Patients will be treated with either Nivo+Ipi, Opdualag, or no treatment pre-surgery (NCT05704933). Following treatment, all subjects will undergo surgical resection of their brain tumors and systemic disease biopsy, if clinically indicated. Post-surgery, all subjects will receive stereotactic radiosurgery (SRS) or fractionated SRS (fSRS), followed by Nivo+Ipi x4 dosages and adjuvant Nivo for 1 year or until disease progression and/or intolerable adverse events. All subjects will be on levetiracetam 500 mg twice a day or equivalent medication throughout the duration of the study. A lumbar puncture for CSF collection will be performed if clinically indicated and CSF and blood collected at different time points. Collected tissue will be send for sc RNA-seq, TCR/BCR seq. A one-way ANOVA will be used to compare the cellular population differences between treatment arms. CNS clinical response will be defined using RANO-BM and i-RANO. Trial is open and actively recruiting. Oxford University Press 2023-08-04 /pmc/articles/PMC10402413/ http://dx.doi.org/10.1093/noajnl/vdad070.135 Text en © The Author(s) 2023. Published by Oxford University Press, the Society for Neuro-Oncology and the European Association of Neuro-Oncology. https://creativecommons.org/licenses/by-nc/4.0/This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial License (https://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@oup.com |
spellingShingle | Final Category: Trials in Progress Pina, Yolanda Chen, Ann Tran, Nam Etame, Arnold Liu, James Furlan, Andre Beer Mokhtari, Sepideh Peguero, Edwin Li, Jiannong Law, Vincent Khushalani, Nikhil Smalley, Inna Vogelbaum, Michael Yu, Michael Arrington, John Macaulay, Robert Tawbi, Hussein Smalley, Keiran Forsyth, Peter TIPS-04 A RANDOMIZED, MULTI-INSTITUTIONAL PILOT STUDY TO EVALUATE THE MOLECULAR AND CELLULAR RESPONSE TO TREATMENT WITH NIVOLUMAB WITH EITHER ADJUVANT IPILIMUMAB OR RELATLIMAB IN ADULT PATIENTS WITH SURGICALLY RESECTABLE MELANOMA BRAIN METASTASES: ONGOING TRIAL |
title | TIPS-04 A RANDOMIZED, MULTI-INSTITUTIONAL PILOT STUDY TO EVALUATE THE MOLECULAR AND CELLULAR RESPONSE TO TREATMENT WITH NIVOLUMAB WITH EITHER ADJUVANT IPILIMUMAB OR RELATLIMAB IN ADULT PATIENTS WITH SURGICALLY RESECTABLE MELANOMA BRAIN METASTASES: ONGOING TRIAL |
title_full | TIPS-04 A RANDOMIZED, MULTI-INSTITUTIONAL PILOT STUDY TO EVALUATE THE MOLECULAR AND CELLULAR RESPONSE TO TREATMENT WITH NIVOLUMAB WITH EITHER ADJUVANT IPILIMUMAB OR RELATLIMAB IN ADULT PATIENTS WITH SURGICALLY RESECTABLE MELANOMA BRAIN METASTASES: ONGOING TRIAL |
title_fullStr | TIPS-04 A RANDOMIZED, MULTI-INSTITUTIONAL PILOT STUDY TO EVALUATE THE MOLECULAR AND CELLULAR RESPONSE TO TREATMENT WITH NIVOLUMAB WITH EITHER ADJUVANT IPILIMUMAB OR RELATLIMAB IN ADULT PATIENTS WITH SURGICALLY RESECTABLE MELANOMA BRAIN METASTASES: ONGOING TRIAL |
title_full_unstemmed | TIPS-04 A RANDOMIZED, MULTI-INSTITUTIONAL PILOT STUDY TO EVALUATE THE MOLECULAR AND CELLULAR RESPONSE TO TREATMENT WITH NIVOLUMAB WITH EITHER ADJUVANT IPILIMUMAB OR RELATLIMAB IN ADULT PATIENTS WITH SURGICALLY RESECTABLE MELANOMA BRAIN METASTASES: ONGOING TRIAL |
title_short | TIPS-04 A RANDOMIZED, MULTI-INSTITUTIONAL PILOT STUDY TO EVALUATE THE MOLECULAR AND CELLULAR RESPONSE TO TREATMENT WITH NIVOLUMAB WITH EITHER ADJUVANT IPILIMUMAB OR RELATLIMAB IN ADULT PATIENTS WITH SURGICALLY RESECTABLE MELANOMA BRAIN METASTASES: ONGOING TRIAL |
title_sort | tips-04 a randomized, multi-institutional pilot study to evaluate the molecular and cellular response to treatment with nivolumab with either adjuvant ipilimumab or relatlimab in adult patients with surgically resectable melanoma brain metastases: ongoing trial |
topic | Final Category: Trials in Progress |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10402413/ http://dx.doi.org/10.1093/noajnl/vdad070.135 |
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