Safety and efficacy of durvalumab (MEDI4736), an anti-programmed cell death ligand-1 immune checkpoint inhibitor, in patients with advanced urothelial bladder cancer

Christophe Massard, Michael S. Gordon, Sunil Sharma, Saeed Rafii, Zev A. Wainberg, Jason Luke, Tyler J. Curiel, Gerardo Colon-Otero, Omid Hamid, Rachel E. Sanborn, Peter H. O'Donnell, Alexandra Drakaki, Winston Tan, John F. Kurland, Marlon C. Rebelatto, Xiaoping Jin, John A. Blake-Haskins, Ashok Gupta, Neil H. Segal

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Abstract

Purpose: To investigate the safety and efficacy of durvalumab, a human monoclonal antibody that binds programmed cell death ligand-1 (PD-L1), and the role of PD-L1 expression on clinical response in patients with advanced urothelial bladder cancer (UBC). Methods: A phase 1/2 multicenter, open-label study is being conducted in patients with inoperable or metastatic solid tumors. We report here the results from the UBC expansion cohort. Durvalumab (MEDI4736, 10 mg/kg every 2 weeks) was administered intravenously for up to 12 months. The primary end point was safety, and objective response rate (ORR, confirmed) was a key secondary end point. An exploratory analysis of pretreatment tumor biopsies led to defining PD-L1-positive as ≥ 25% of tumor cells or tumor-infiltrating immune cells expressing membrane PD-L1. Results: A total of 61 patients (40 PD-L1-positive, 21 PD-L1-negative), 93.4% of whom received one or more prior therapies for advanced disease, were treated (median duration of follow-up, 4.3 months). The most common treatment-related adverse events (AEs) of any grade were fatigue (13.1%), diarrhea (9.8%), and decreased appetite (8.2%). Grade 3 treatment-related AEs occurred in three patients (4.9%); there were no treatment-related grade 4 or 5 AEs. One treatment-related AE (acute kidney injury) resulted in treatment discontinuation. The ORR was 31.0% (95% CI, 17.6 to 47.1) in 42 response-evaluable patients, 46.4% (95% CI, 27.5 to 66.1) in the PD-L1-positive subgroup, and 0% (95% CI, 0.0 to 23.2) in the PD-L1-negative subgroup. Responses are ongoing in 12 of 13 responding patients, with median duration of response not yet reached (range, 4.1+ to 49.3+ weeks). Conclusion: Durvalumab demonstrated a manageable safety profile and evidence of meaningful clinical activity in PD-L1-positive patients with UBC, many of whom were heavily pretreated.

Original languageEnglish (US)
Pages (from-to)3119-3125
Number of pages7
JournalJournal of Clinical Oncology
Volume34
Issue number26
DOIs
StatePublished - Sep 10 2016

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Urinary Bladder Neoplasms
Cell Death
Ligands
Safety
CD274 Antigen
Neoplasms
Therapeutics
MEDI4736
Appetite
Acute Kidney Injury
Fatigue
Diarrhea
Monoclonal Antibodies
Cell Membrane
Biopsy

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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Safety and efficacy of durvalumab (MEDI4736), an anti-programmed cell death ligand-1 immune checkpoint inhibitor, in patients with advanced urothelial bladder cancer. / Massard, Christophe; Gordon, Michael S.; Sharma, Sunil; Rafii, Saeed; Wainberg, Zev A.; Luke, Jason; Curiel, Tyler J.; Colon-Otero, Gerardo; Hamid, Omid; Sanborn, Rachel E.; O'Donnell, Peter H.; Drakaki, Alexandra; Tan, Winston; Kurland, John F.; Rebelatto, Marlon C.; Jin, Xiaoping; Blake-Haskins, John A.; Gupta, Ashok; Segal, Neil H.

In: Journal of Clinical Oncology, Vol. 34, No. 26, 10.09.2016, p. 3119-3125.

Research output: Contribution to journalArticle

Massard, C, Gordon, MS, Sharma, S, Rafii, S, Wainberg, ZA, Luke, J, Curiel, TJ, Colon-Otero, G, Hamid, O, Sanborn, RE, O'Donnell, PH, Drakaki, A, Tan, W, Kurland, JF, Rebelatto, MC, Jin, X, Blake-Haskins, JA, Gupta, A & Segal, NH 2016, 'Safety and efficacy of durvalumab (MEDI4736), an anti-programmed cell death ligand-1 immune checkpoint inhibitor, in patients with advanced urothelial bladder cancer', Journal of Clinical Oncology, vol. 34, no. 26, pp. 3119-3125. https://doi.org/10.1200/JCO.2016.67.9761
Massard, Christophe ; Gordon, Michael S. ; Sharma, Sunil ; Rafii, Saeed ; Wainberg, Zev A. ; Luke, Jason ; Curiel, Tyler J. ; Colon-Otero, Gerardo ; Hamid, Omid ; Sanborn, Rachel E. ; O'Donnell, Peter H. ; Drakaki, Alexandra ; Tan, Winston ; Kurland, John F. ; Rebelatto, Marlon C. ; Jin, Xiaoping ; Blake-Haskins, John A. ; Gupta, Ashok ; Segal, Neil H. / Safety and efficacy of durvalumab (MEDI4736), an anti-programmed cell death ligand-1 immune checkpoint inhibitor, in patients with advanced urothelial bladder cancer. In: Journal of Clinical Oncology. 2016 ; Vol. 34, No. 26. pp. 3119-3125.
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abstract = "Purpose: To investigate the safety and efficacy of durvalumab, a human monoclonal antibody that binds programmed cell death ligand-1 (PD-L1), and the role of PD-L1 expression on clinical response in patients with advanced urothelial bladder cancer (UBC). Methods: A phase 1/2 multicenter, open-label study is being conducted in patients with inoperable or metastatic solid tumors. We report here the results from the UBC expansion cohort. Durvalumab (MEDI4736, 10 mg/kg every 2 weeks) was administered intravenously for up to 12 months. The primary end point was safety, and objective response rate (ORR, confirmed) was a key secondary end point. An exploratory analysis of pretreatment tumor biopsies led to defining PD-L1-positive as ≥ 25{\%} of tumor cells or tumor-infiltrating immune cells expressing membrane PD-L1. Results: A total of 61 patients (40 PD-L1-positive, 21 PD-L1-negative), 93.4{\%} of whom received one or more prior therapies for advanced disease, were treated (median duration of follow-up, 4.3 months). The most common treatment-related adverse events (AEs) of any grade were fatigue (13.1{\%}), diarrhea (9.8{\%}), and decreased appetite (8.2{\%}). Grade 3 treatment-related AEs occurred in three patients (4.9{\%}); there were no treatment-related grade 4 or 5 AEs. One treatment-related AE (acute kidney injury) resulted in treatment discontinuation. The ORR was 31.0{\%} (95{\%} CI, 17.6 to 47.1) in 42 response-evaluable patients, 46.4{\%} (95{\%} CI, 27.5 to 66.1) in the PD-L1-positive subgroup, and 0{\%} (95{\%} CI, 0.0 to 23.2) in the PD-L1-negative subgroup. Responses are ongoing in 12 of 13 responding patients, with median duration of response not yet reached (range, 4.1+ to 49.3+ weeks). Conclusion: Durvalumab demonstrated a manageable safety profile and evidence of meaningful clinical activity in PD-L1-positive patients with UBC, many of whom were heavily pretreated.",
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T1 - Safety and efficacy of durvalumab (MEDI4736), an anti-programmed cell death ligand-1 immune checkpoint inhibitor, in patients with advanced urothelial bladder cancer

AU - Massard, Christophe

AU - Gordon, Michael S.

AU - Sharma, Sunil

AU - Rafii, Saeed

AU - Wainberg, Zev A.

AU - Luke, Jason

AU - Curiel, Tyler J.

AU - Colon-Otero, Gerardo

AU - Hamid, Omid

AU - Sanborn, Rachel E.

AU - O'Donnell, Peter H.

AU - Drakaki, Alexandra

AU - Tan, Winston

AU - Kurland, John F.

AU - Rebelatto, Marlon C.

AU - Jin, Xiaoping

AU - Blake-Haskins, John A.

AU - Gupta, Ashok

AU - Segal, Neil H.

PY - 2016/9/10

Y1 - 2016/9/10

N2 - Purpose: To investigate the safety and efficacy of durvalumab, a human monoclonal antibody that binds programmed cell death ligand-1 (PD-L1), and the role of PD-L1 expression on clinical response in patients with advanced urothelial bladder cancer (UBC). Methods: A phase 1/2 multicenter, open-label study is being conducted in patients with inoperable or metastatic solid tumors. We report here the results from the UBC expansion cohort. Durvalumab (MEDI4736, 10 mg/kg every 2 weeks) was administered intravenously for up to 12 months. The primary end point was safety, and objective response rate (ORR, confirmed) was a key secondary end point. An exploratory analysis of pretreatment tumor biopsies led to defining PD-L1-positive as ≥ 25% of tumor cells or tumor-infiltrating immune cells expressing membrane PD-L1. Results: A total of 61 patients (40 PD-L1-positive, 21 PD-L1-negative), 93.4% of whom received one or more prior therapies for advanced disease, were treated (median duration of follow-up, 4.3 months). The most common treatment-related adverse events (AEs) of any grade were fatigue (13.1%), diarrhea (9.8%), and decreased appetite (8.2%). Grade 3 treatment-related AEs occurred in three patients (4.9%); there were no treatment-related grade 4 or 5 AEs. One treatment-related AE (acute kidney injury) resulted in treatment discontinuation. The ORR was 31.0% (95% CI, 17.6 to 47.1) in 42 response-evaluable patients, 46.4% (95% CI, 27.5 to 66.1) in the PD-L1-positive subgroup, and 0% (95% CI, 0.0 to 23.2) in the PD-L1-negative subgroup. Responses are ongoing in 12 of 13 responding patients, with median duration of response not yet reached (range, 4.1+ to 49.3+ weeks). Conclusion: Durvalumab demonstrated a manageable safety profile and evidence of meaningful clinical activity in PD-L1-positive patients with UBC, many of whom were heavily pretreated.

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