Cargando…

Phase 2 Trial of Nivolumab and Ramucirumab for Relapsed Mesothelioma: HCRN-LUN15-299

INTRODUCTION: We hypothesized that ramucirumab could increase previously reported objective response rate (ORR) of 11% of single-agent nivolumab in the second-line therapy of unresectable mesothelioma. METHODS: This was a cooperative group, single-arm, phase 2 trial enrolling patients with unresecta...

Descripción completa

Detalles Bibliográficos
Autores principales: Dudek, Arkadiusz Z., Xi, Min X., Scilla, Katherine A., Mamdani, Hirva, Creelan, Benjamin C., Saltos, Andreas, Tanvetyanon, Tawee, Chiappori, Alberto
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10689266/
https://www.ncbi.nlm.nih.gov/pubmed/38046376
http://dx.doi.org/10.1016/j.jtocrr.2023.100584
_version_ 1785152335280865280
author Dudek, Arkadiusz Z.
Xi, Min X.
Scilla, Katherine A.
Mamdani, Hirva
Creelan, Benjamin C.
Saltos, Andreas
Tanvetyanon, Tawee
Chiappori, Alberto
author_facet Dudek, Arkadiusz Z.
Xi, Min X.
Scilla, Katherine A.
Mamdani, Hirva
Creelan, Benjamin C.
Saltos, Andreas
Tanvetyanon, Tawee
Chiappori, Alberto
author_sort Dudek, Arkadiusz Z.
collection PubMed
description INTRODUCTION: We hypothesized that ramucirumab could increase previously reported objective response rate (ORR) of 11% of single-agent nivolumab in the second-line therapy of unresectable mesothelioma. METHODS: This was a cooperative group, single-arm, phase 2 trial enrolling patients with unresectable mesothelioma after progression on more than or equal to one pemetrexed-containing regimen. Ramucirumab and nivolumab were given intravenously every 14 days for up to 24 months. The primary end point was ORR; secondary end points were progression-free survival (PFS) rate at 24 weeks and overall survival (OS). RESULTS: Between April 2018 and October 2021, 34 patients were recruited. Median age was 72 (range: 40–89) years, 12% were women, and 79% of tumors had epithelial histology. Median follow-up was 10.2 months (interquartile range 19.6 mo [4.3–23.8]). ORR was 22.6% (95% confidence interval [CI]: 9.6%–41.1%) in all population and 43% (95% CI: 10%–82%) in patients with nonepithelioid histology. Of all patients, 45.2% (95% CI: 27.3%–64.0%) had stable disease. PFS rate at 24 weeks was 32% (95% CI: 17%–51%). Median PFS was 4.2 months (95% CI: 1.9–6.4 mo). Median OS was 12.5 months (95% CI: 6.3–23.5 mo). There was no grade greater than or equal to four toxicity. Programmed death-ligand 1 expression in the tumor did not correlate with benefit from treatment. Activation of tumor-infiltrating lymphocytes in response to treatment was associated with a trend toward improvement in PFS. CONCLUSIONS: Nivolumab and ramucirumab combination was safe and generated PFS and OS rates and ORR that compare favorably with single-agent nivolumab in a similar patient population. The primary end point of 40% ORR was not reached. Further investigation of this regimen in mesothelioma with nonepithelioid histology may be warranted. Clinical Trial Information: NCT03502746.
format Online
Article
Text
id pubmed-10689266
institution National Center for Biotechnology Information
language English
publishDate 2023
publisher Elsevier
record_format MEDLINE/PubMed
spelling pubmed-106892662023-12-02 Phase 2 Trial of Nivolumab and Ramucirumab for Relapsed Mesothelioma: HCRN-LUN15-299 Dudek, Arkadiusz Z. Xi, Min X. Scilla, Katherine A. Mamdani, Hirva Creelan, Benjamin C. Saltos, Andreas Tanvetyanon, Tawee Chiappori, Alberto JTO Clin Res Rep Original Article INTRODUCTION: We hypothesized that ramucirumab could increase previously reported objective response rate (ORR) of 11% of single-agent nivolumab in the second-line therapy of unresectable mesothelioma. METHODS: This was a cooperative group, single-arm, phase 2 trial enrolling patients with unresectable mesothelioma after progression on more than or equal to one pemetrexed-containing regimen. Ramucirumab and nivolumab were given intravenously every 14 days for up to 24 months. The primary end point was ORR; secondary end points were progression-free survival (PFS) rate at 24 weeks and overall survival (OS). RESULTS: Between April 2018 and October 2021, 34 patients were recruited. Median age was 72 (range: 40–89) years, 12% were women, and 79% of tumors had epithelial histology. Median follow-up was 10.2 months (interquartile range 19.6 mo [4.3–23.8]). ORR was 22.6% (95% confidence interval [CI]: 9.6%–41.1%) in all population and 43% (95% CI: 10%–82%) in patients with nonepithelioid histology. Of all patients, 45.2% (95% CI: 27.3%–64.0%) had stable disease. PFS rate at 24 weeks was 32% (95% CI: 17%–51%). Median PFS was 4.2 months (95% CI: 1.9–6.4 mo). Median OS was 12.5 months (95% CI: 6.3–23.5 mo). There was no grade greater than or equal to four toxicity. Programmed death-ligand 1 expression in the tumor did not correlate with benefit from treatment. Activation of tumor-infiltrating lymphocytes in response to treatment was associated with a trend toward improvement in PFS. CONCLUSIONS: Nivolumab and ramucirumab combination was safe and generated PFS and OS rates and ORR that compare favorably with single-agent nivolumab in a similar patient population. The primary end point of 40% ORR was not reached. Further investigation of this regimen in mesothelioma with nonepithelioid histology may be warranted. Clinical Trial Information: NCT03502746. Elsevier 2023-10-12 /pmc/articles/PMC10689266/ /pubmed/38046376 http://dx.doi.org/10.1016/j.jtocrr.2023.100584 Text en © 2023 The Authors https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
spellingShingle Original Article
Dudek, Arkadiusz Z.
Xi, Min X.
Scilla, Katherine A.
Mamdani, Hirva
Creelan, Benjamin C.
Saltos, Andreas
Tanvetyanon, Tawee
Chiappori, Alberto
Phase 2 Trial of Nivolumab and Ramucirumab for Relapsed Mesothelioma: HCRN-LUN15-299
title Phase 2 Trial of Nivolumab and Ramucirumab for Relapsed Mesothelioma: HCRN-LUN15-299
title_full Phase 2 Trial of Nivolumab and Ramucirumab for Relapsed Mesothelioma: HCRN-LUN15-299
title_fullStr Phase 2 Trial of Nivolumab and Ramucirumab for Relapsed Mesothelioma: HCRN-LUN15-299
title_full_unstemmed Phase 2 Trial of Nivolumab and Ramucirumab for Relapsed Mesothelioma: HCRN-LUN15-299
title_short Phase 2 Trial of Nivolumab and Ramucirumab for Relapsed Mesothelioma: HCRN-LUN15-299
title_sort phase 2 trial of nivolumab and ramucirumab for relapsed mesothelioma: hcrn-lun15-299
topic Original Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10689266/
https://www.ncbi.nlm.nih.gov/pubmed/38046376
http://dx.doi.org/10.1016/j.jtocrr.2023.100584
work_keys_str_mv AT dudekarkadiuszz phase2trialofnivolumabandramucirumabforrelapsedmesotheliomahcrnlun15299
AT ximinx phase2trialofnivolumabandramucirumabforrelapsedmesotheliomahcrnlun15299
AT scillakatherinea phase2trialofnivolumabandramucirumabforrelapsedmesotheliomahcrnlun15299
AT mamdanihirva phase2trialofnivolumabandramucirumabforrelapsedmesotheliomahcrnlun15299
AT creelanbenjaminc phase2trialofnivolumabandramucirumabforrelapsedmesotheliomahcrnlun15299
AT saltosandreas phase2trialofnivolumabandramucirumabforrelapsedmesotheliomahcrnlun15299
AT tanvetyanontawee phase2trialofnivolumabandramucirumabforrelapsedmesotheliomahcrnlun15299
AT chiapporialberto phase2trialofnivolumabandramucirumabforrelapsedmesotheliomahcrnlun15299