Cargando…

Phase Ib/II Clinical Trial of Pembrolizumab With Bevacizumab for Metastatic Renal Cell Carcinoma: BTCRC-GU14-003

PURPOSE: We hypothesized that bevacizumab will potentiate activity of pembrolizumab. We conducted a phase Ib/II, single-arm, multisite clinical trial of the combination in metastatic renal cell carcinoma (RCC). PATIENTS AND METHODS: Patients with metastatic clear cell RCC who experienced progression...

Descripción completa

Detalles Bibliográficos
Autores principales: Dudek, Arkadiusz Z., Liu, Li C., Gupta, Shilpa, Logan, Theodore F., Singer, Eric A., Joshi, Monika, Zakharia, Yousef N., Lang, Joshua M., Schwarz, James K., Al-Janadi, Anas, Alva, Ajjai S.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Society of Clinical Oncology 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7145584/
https://www.ncbi.nlm.nih.gov/pubmed/32097091
http://dx.doi.org/10.1200/JCO.19.02394
_version_ 1783520019723845632
author Dudek, Arkadiusz Z.
Liu, Li C.
Gupta, Shilpa
Logan, Theodore F.
Singer, Eric A.
Joshi, Monika
Zakharia, Yousef N.
Lang, Joshua M.
Schwarz, James K.
Al-Janadi, Anas
Alva, Ajjai S.
author_facet Dudek, Arkadiusz Z.
Liu, Li C.
Gupta, Shilpa
Logan, Theodore F.
Singer, Eric A.
Joshi, Monika
Zakharia, Yousef N.
Lang, Joshua M.
Schwarz, James K.
Al-Janadi, Anas
Alva, Ajjai S.
author_sort Dudek, Arkadiusz Z.
collection PubMed
description PURPOSE: We hypothesized that bevacizumab will potentiate activity of pembrolizumab. We conducted a phase Ib/II, single-arm, multisite clinical trial of the combination in metastatic renal cell carcinoma (RCC). PATIENTS AND METHODS: Patients with metastatic clear cell RCC who experienced progression after at least one systemic therapy (phase Ib) or were treatment naïve (phase II) were enrolled. In phase Ib, pembrolizumab (200 mg) and bevacizumab (10 or 15 mg/kg) were given intravenously every 3 weeks. The primary end point for phase II was overall response rate (ORR). With an 80% statistical power and a type I error probability of 0.1, 48 patients were to be accrued to detect an ORR of 42%. RESULTS: Thirteen patients (ages 33-68 years; median, 55 years) were enrolled in the phase Ib study. No dose-limiting toxicities were reported. Pembrolizumab 200 mg and bevacizumab 15 mg/kg were chosen for phase II. Forty-eight patients (ages 42-84 years; median age, 61 years; 33 males) were accrued for the phase II study. The primary end point was met, with the ORR reaching 60.9% (95% CI, 45.4% to 74.9%), consisting of 1 complete response (CR), 2 CRs in target lesions, 25 partial responses, 18 responses of stable disease, 2 unevaluable responses. Median progression-free survival was 20.7 months (95% CI, 11.3 to 27.4 months). Median overall survival was not reached at the median follow-up of 28.3 months. The most common treatment-related grade 3 toxicities were hypertension and proteinuria. There were two grade 4 toxicities: duodenal ulcer and hyponatremia. Presence of tumor-infiltrating T cells, but not programmed death-ligand 1 expression, in tumor tissue correlated with response. CONCLUSION: The combination of 200 mg of pembrolizumab and a 15 mg/kg dose of bevacizumab given every 3 weeks is safe and active in metastatic RCC.
format Online
Article
Text
id pubmed-7145584
institution National Center for Biotechnology Information
language English
publishDate 2020
publisher American Society of Clinical Oncology
record_format MEDLINE/PubMed
spelling pubmed-71455842020-04-10 Phase Ib/II Clinical Trial of Pembrolizumab With Bevacizumab for Metastatic Renal Cell Carcinoma: BTCRC-GU14-003 Dudek, Arkadiusz Z. Liu, Li C. Gupta, Shilpa Logan, Theodore F. Singer, Eric A. Joshi, Monika Zakharia, Yousef N. Lang, Joshua M. Schwarz, James K. Al-Janadi, Anas Alva, Ajjai S. J Clin Oncol ORIGINAL REPORTS PURPOSE: We hypothesized that bevacizumab will potentiate activity of pembrolizumab. We conducted a phase Ib/II, single-arm, multisite clinical trial of the combination in metastatic renal cell carcinoma (RCC). PATIENTS AND METHODS: Patients with metastatic clear cell RCC who experienced progression after at least one systemic therapy (phase Ib) or were treatment naïve (phase II) were enrolled. In phase Ib, pembrolizumab (200 mg) and bevacizumab (10 or 15 mg/kg) were given intravenously every 3 weeks. The primary end point for phase II was overall response rate (ORR). With an 80% statistical power and a type I error probability of 0.1, 48 patients were to be accrued to detect an ORR of 42%. RESULTS: Thirteen patients (ages 33-68 years; median, 55 years) were enrolled in the phase Ib study. No dose-limiting toxicities were reported. Pembrolizumab 200 mg and bevacizumab 15 mg/kg were chosen for phase II. Forty-eight patients (ages 42-84 years; median age, 61 years; 33 males) were accrued for the phase II study. The primary end point was met, with the ORR reaching 60.9% (95% CI, 45.4% to 74.9%), consisting of 1 complete response (CR), 2 CRs in target lesions, 25 partial responses, 18 responses of stable disease, 2 unevaluable responses. Median progression-free survival was 20.7 months (95% CI, 11.3 to 27.4 months). Median overall survival was not reached at the median follow-up of 28.3 months. The most common treatment-related grade 3 toxicities were hypertension and proteinuria. There were two grade 4 toxicities: duodenal ulcer and hyponatremia. Presence of tumor-infiltrating T cells, but not programmed death-ligand 1 expression, in tumor tissue correlated with response. CONCLUSION: The combination of 200 mg of pembrolizumab and a 15 mg/kg dose of bevacizumab given every 3 weeks is safe and active in metastatic RCC. American Society of Clinical Oncology 2020-04-10 2020-02-25 /pmc/articles/PMC7145584/ /pubmed/32097091 http://dx.doi.org/10.1200/JCO.19.02394 Text en © 2020 by American Society of Clinical Oncology https://creativecommons.org/licenses/by-nc-nd/4.0/ Creative Commons Attribution Non-Commercial No Derivatives 4.0 License: https://creativecommons.org/licenses/by-nc-nd/4.0/
spellingShingle ORIGINAL REPORTS
Dudek, Arkadiusz Z.
Liu, Li C.
Gupta, Shilpa
Logan, Theodore F.
Singer, Eric A.
Joshi, Monika
Zakharia, Yousef N.
Lang, Joshua M.
Schwarz, James K.
Al-Janadi, Anas
Alva, Ajjai S.
Phase Ib/II Clinical Trial of Pembrolizumab With Bevacizumab for Metastatic Renal Cell Carcinoma: BTCRC-GU14-003
title Phase Ib/II Clinical Trial of Pembrolizumab With Bevacizumab for Metastatic Renal Cell Carcinoma: BTCRC-GU14-003
title_full Phase Ib/II Clinical Trial of Pembrolizumab With Bevacizumab for Metastatic Renal Cell Carcinoma: BTCRC-GU14-003
title_fullStr Phase Ib/II Clinical Trial of Pembrolizumab With Bevacizumab for Metastatic Renal Cell Carcinoma: BTCRC-GU14-003
title_full_unstemmed Phase Ib/II Clinical Trial of Pembrolizumab With Bevacizumab for Metastatic Renal Cell Carcinoma: BTCRC-GU14-003
title_short Phase Ib/II Clinical Trial of Pembrolizumab With Bevacizumab for Metastatic Renal Cell Carcinoma: BTCRC-GU14-003
title_sort phase ib/ii clinical trial of pembrolizumab with bevacizumab for metastatic renal cell carcinoma: btcrc-gu14-003
topic ORIGINAL REPORTS
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7145584/
https://www.ncbi.nlm.nih.gov/pubmed/32097091
http://dx.doi.org/10.1200/JCO.19.02394
work_keys_str_mv AT dudekarkadiuszz phaseibiiclinicaltrialofpembrolizumabwithbevacizumabformetastaticrenalcellcarcinomabtcrcgu14003
AT liulic phaseibiiclinicaltrialofpembrolizumabwithbevacizumabformetastaticrenalcellcarcinomabtcrcgu14003
AT guptashilpa phaseibiiclinicaltrialofpembrolizumabwithbevacizumabformetastaticrenalcellcarcinomabtcrcgu14003
AT logantheodoref phaseibiiclinicaltrialofpembrolizumabwithbevacizumabformetastaticrenalcellcarcinomabtcrcgu14003
AT singererica phaseibiiclinicaltrialofpembrolizumabwithbevacizumabformetastaticrenalcellcarcinomabtcrcgu14003
AT joshimonika phaseibiiclinicaltrialofpembrolizumabwithbevacizumabformetastaticrenalcellcarcinomabtcrcgu14003
AT zakhariayousefn phaseibiiclinicaltrialofpembrolizumabwithbevacizumabformetastaticrenalcellcarcinomabtcrcgu14003
AT langjoshuam phaseibiiclinicaltrialofpembrolizumabwithbevacizumabformetastaticrenalcellcarcinomabtcrcgu14003
AT schwarzjamesk phaseibiiclinicaltrialofpembrolizumabwithbevacizumabformetastaticrenalcellcarcinomabtcrcgu14003
AT aljanadianas phaseibiiclinicaltrialofpembrolizumabwithbevacizumabformetastaticrenalcellcarcinomabtcrcgu14003
AT alvaajjais phaseibiiclinicaltrialofpembrolizumabwithbevacizumabformetastaticrenalcellcarcinomabtcrcgu14003