title: Avelumab, an Anti-Programmed Death-Ligand 1 Antibody, In Patients With Refractory Metastatic Urothelial Carcinoma: Results From a Multicenter, Phase Ib Study.
abstract: Purpose We assessed the safety and antitumor activity of avelumab, a fully human anti-programmed death-ligand 1 (PD-L1) IgG1 antibody, in patients with refractory metastatic urothelial carcinoma. Methods In this phase Ib, multicenter, expansion cohort, patients with urothelial carcinoma progressing after platinum-based chemotherapy and unselected for PD-L1 expression received avelumab 10 mg/kg intravenously every 2 weeks. The primary objectives were safety and tolerability. Secondary objectives included confirmed objective response rate (Response Evaluation Criteria in Solid Tumors [RECIST] version 1.1), progression-free survival, overall survival (OS), and PD-L1-associated clinical activity. PD-L1 positivity was defined as expression by immunohistochemistry on ≥ 5% of tumor cells. Results Forty-four patients were treated with avelumab and followed for a median of 16.5 months (interquartile range, 15.8 to 16.7 months). The data cutoff was March 19, 2016. The most frequent treatment-related adverse events of any grade were fatigue/asthenia (31.8%), infusion-related reaction (20.5%), and nausea (11.4%). Grades 3 to 4 treatment-related adverse events occurred in three patients (6.8%) and included asthenia, AST elevation, creatine phosphokinase elevation, and decreased appetite. The confirmed objective response rate by independent central review was 18.2% (95% CI, 8.2% to 32.7%; five complete responses and three partial responses). The median duration of response was not reached (95% CI, 12.1 weeks to not estimable), and responses were ongoing in six patients (75.0%), including four of five complete responses. Seven of eight responding patients had PD-L1-positive tumors. The median progression-free survival was 11.6 weeks (95% CI, 6.1 to 17.4 weeks); the median OS was 13.7 months (95% CI, 8.5 months to not estimable), with a 12-month OS rate of 54.3% (95% CI, 37.9% to 68.1%). Conclusion Avelumab was well tolerated and associated with durable responses and prolonged survival in patients with refractory metastatic UC.
authors.affiliation: Andrea B. Apolo and James L. Gulley, National Institutes of Health, Bethesda, MD; Jeffrey R. Infante, Sarah Cannon Research Institute/Tennessee Oncology, Nashville, TN; Ani Balmanoukian, The Angeles Clinic & Research Institute; Alain C. Mita, Cedars Sinai Medical Center, Los Angeles; Karen Kelly, University of California-Davis, Sacramento; Marko Srdanov, Dako North America, Carpinteria, CA; Manish R. Patel, Florida Cancer Specialists & Research Institute, Sarasota, FL; Ding Wang, Henry Ford Hospital, Detroit, MI; Anthony E. Mega, The Warren Alpert Medical School at Brown University; Howard Safran, The Miriam Hospital, Providence; Howard Safran, Newport Hospital, Newport, RI; Carolyn D. Britten, Medical University of South Carolina, Charleston, SC; Alain Ravaud, CHU de Bordeaux, Bordeaux, France; Thomas E. Stinchcombe, Duke University Medical Center, Durham, NC; Arnold B. Gelb and Kevin Chin, EMD Serono, Billerica, MA; and Michael Schlichting, Merck, Darmstadt, Germany.
authors.forename: Andrea B
authors.initials: AB
authors.lastname: Apolo
authors.affiliation: Andrea B. Apolo and James L. Gulley, National Institutes of Health, Bethesda, MD; Jeffrey R. Infante, Sarah Cannon Research Institute/Tennessee Oncology, Nashville, TN; Ani Balmanoukian, The Angeles Clinic & Research Institute; Alain C. Mita, Cedars Sinai Medical Center, Los Angeles; Karen Kelly, University of California-Davis, Sacramento; Marko Srdanov, Dako North America, Carpinteria, CA; Manish R. Patel, Florida Cancer Specialists & Research Institute, Sarasota, FL; Ding Wang, Henry Ford Hospital, Detroit, MI; Anthony E. Mega, The Warren Alpert Medical School at Brown University; Howard Safran, The Miriam Hospital, Providence; Howard Safran, Newport Hospital, Newport, RI; Carolyn D. Britten, Medical University of South Carolina, Charleston, SC; Alain Ravaud, CHU de Bordeaux, Bordeaux, France; Thomas E. Stinchcombe, Duke University Medical Center, Durham, NC; Arnold B. Gelb and Kevin Chin, EMD Serono, Billerica, MA; and Michael Schlichting, Merck, Darmstadt, Germany.
authors.forename: Jeffrey R
authors.initials: JR
authors.lastname: Infante
authors.affiliation: Andrea B. Apolo and James L. Gulley, National Institutes of Health, Bethesda, MD; Jeffrey R. Infante, Sarah Cannon Research Institute/Tennessee Oncology, Nashville, TN; Ani Balmanoukian, The Angeles Clinic & Research Institute; Alain C. Mita, Cedars Sinai Medical Center, Los Angeles; Karen Kelly, University of California-Davis, Sacramento; Marko Srdanov, Dako North America, Carpinteria, CA; Manish R. Patel, Florida Cancer Specialists & Research Institute, Sarasota, FL; Ding Wang, Henry Ford Hospital, Detroit, MI; Anthony E. Mega, The Warren Alpert Medical School at Brown University; Howard Safran, The Miriam Hospital, Providence; Howard Safran, Newport Hospital, Newport, RI; Carolyn D. Britten, Medical University of South Carolina, Charleston, SC; Alain Ravaud, CHU de Bordeaux, Bordeaux, France; Thomas E. Stinchcombe, Duke University Medical Center, Durham, NC; Arnold B. Gelb and Kevin Chin, EMD Serono, Billerica, MA; and Michael Schlichting, Merck, Darmstadt, Germany.
authors.forename: Ani
authors.initials: A
authors.lastname: Balmanoukian
authors.affiliation: Andrea B. Apolo and James L. Gulley, National Institutes of Health, Bethesda, MD; Jeffrey R. Infante, Sarah Cannon Research Institute/Tennessee Oncology, Nashville, TN; Ani Balmanoukian, The Angeles Clinic & Research Institute; Alain C. Mita, Cedars Sinai Medical Center, Los Angeles; Karen Kelly, University of California-Davis, Sacramento; Marko Srdanov, Dako North America, Carpinteria, CA; Manish R. Patel, Florida Cancer Specialists & Research Institute, Sarasota, FL; Ding Wang, Henry Ford Hospital, Detroit, MI; Anthony E. Mega, The Warren Alpert Medical School at Brown University; Howard Safran, The Miriam Hospital, Providence; Howard Safran, Newport Hospital, Newport, RI; Carolyn D. Britten, Medical University of South Carolina, Charleston, SC; Alain Ravaud, CHU de Bordeaux, Bordeaux, France; Thomas E. Stinchcombe, Duke University Medical Center, Durham, NC; Arnold B. Gelb and Kevin Chin, EMD Serono, Billerica, MA; and Michael Schlichting, Merck, Darmstadt, Germany.
authors.forename: Manish R
authors.initials: MR
authors.lastname: Patel
authors.affiliation: Andrea B. Apolo and James L. Gulley, National Institutes of Health, Bethesda, MD; Jeffrey R. Infante, Sarah Cannon Research Institute/Tennessee Oncology, Nashville, TN; Ani Balmanoukian, The Angeles Clinic & Research Institute; Alain C. Mita, Cedars Sinai Medical Center, Los Angeles; Karen Kelly, University of California-Davis, Sacramento; Marko Srdanov, Dako North America, Carpinteria, CA; Manish R. Patel, Florida Cancer Specialists & Research Institute, Sarasota, FL; Ding Wang, Henry Ford Hospital, Detroit, MI; Anthony E. Mega, The Warren Alpert Medical School at Brown University; Howard Safran, The Miriam Hospital, Providence; Howard Safran, Newport Hospital, Newport, RI; Carolyn D. Britten, Medical University of South Carolina, Charleston, SC; Alain Ravaud, CHU de Bordeaux, Bordeaux, France; Thomas E. Stinchcombe, Duke University Medical Center, Durham, NC; Arnold B. Gelb and Kevin Chin, EMD Serono, Billerica, MA; and Michael Schlichting, Merck, Darmstadt, Germany.
authors.forename: Ding
authors.initials: D
authors.lastname: Wang
authors.affiliation: Andrea B. Apolo and James L. Gulley, National Institutes of Health, Bethesda, MD; Jeffrey R. Infante, Sarah Cannon Research Institute/Tennessee Oncology, Nashville, TN; Ani Balmanoukian, The Angeles Clinic & Research Institute; Alain C. Mita, Cedars Sinai Medical Center, Los Angeles; Karen Kelly, University of California-Davis, Sacramento; Marko Srdanov, Dako North America, Carpinteria, CA; Manish R. Patel, Florida Cancer Specialists & Research Institute, Sarasota, FL; Ding Wang, Henry Ford Hospital, Detroit, MI; Anthony E. Mega, The Warren Alpert Medical School at Brown University; Howard Safran, The Miriam Hospital, Providence; Howard Safran, Newport Hospital, Newport, RI; Carolyn D. Britten, Medical University of South Carolina, Charleston, SC; Alain Ravaud, CHU de Bordeaux, Bordeaux, France; Thomas E. Stinchcombe, Duke University Medical Center, Durham, NC; Arnold B. Gelb and Kevin Chin, EMD Serono, Billerica, MA; and Michael Schlichting, Merck, Darmstadt, Germany.
authors.forename: Karen
authors.initials: K
authors.lastname: Kelly
authors.affiliation: Andrea B. Apolo and James L. Gulley, National Institutes of Health, Bethesda, MD; Jeffrey R. Infante, Sarah Cannon Research Institute/Tennessee Oncology, Nashville, TN; Ani Balmanoukian, The Angeles Clinic & Research Institute; Alain C. Mita, Cedars Sinai Medical Center, Los Angeles; Karen Kelly, University of California-Davis, Sacramento; Marko Srdanov, Dako North America, Carpinteria, CA; Manish R. Patel, Florida Cancer Specialists & Research Institute, Sarasota, FL; Ding Wang, Henry Ford Hospital, Detroit, MI; Anthony E. Mega, The Warren Alpert Medical School at Brown University; Howard Safran, The Miriam Hospital, Providence; Howard Safran, Newport Hospital, Newport, RI; Carolyn D. Britten, Medical University of South Carolina, Charleston, SC; Alain Ravaud, CHU de Bordeaux, Bordeaux, France; Thomas E. Stinchcombe, Duke University Medical Center, Durham, NC; Arnold B. Gelb and Kevin Chin, EMD Serono, Billerica, MA; and Michael Schlichting, Merck, Darmstadt, Germany.
authors.forename: Anthony E
authors.initials: AE
authors.lastname: Mega
authors.affiliation: Andrea B. Apolo and James L. Gulley, National Institutes of Health, Bethesda, MD; Jeffrey R. Infante, Sarah Cannon Research Institute/Tennessee Oncology, Nashville, TN; Ani Balmanoukian, The Angeles Clinic & Research Institute; Alain C. Mita, Cedars Sinai Medical Center, Los Angeles; Karen Kelly, University of California-Davis, Sacramento; Marko Srdanov, Dako North America, Carpinteria, CA; Manish R. Patel, Florida Cancer Specialists & Research Institute, Sarasota, FL; Ding Wang, Henry Ford Hospital, Detroit, MI; Anthony E. Mega, The Warren Alpert Medical School at Brown University; Howard Safran, The Miriam Hospital, Providence; Howard Safran, Newport Hospital, Newport, RI; Carolyn D. Britten, Medical University of South Carolina, Charleston, SC; Alain Ravaud, CHU de Bordeaux, Bordeaux, France; Thomas E. Stinchcombe, Duke University Medical Center, Durham, NC; Arnold B. Gelb and Kevin Chin, EMD Serono, Billerica, MA; and Michael Schlichting, Merck, Darmstadt, Germany.
authors.forename: Carolyn D
authors.initials: CD
authors.lastname: Britten
authors.affiliation: Andrea B. Apolo and James L. Gulley, National Institutes of Health, Bethesda, MD; Jeffrey R. Infante, Sarah Cannon Research Institute/Tennessee Oncology, Nashville, TN; Ani Balmanoukian, The Angeles Clinic & Research Institute; Alain C. Mita, Cedars Sinai Medical Center, Los Angeles; Karen Kelly, University of California-Davis, Sacramento; Marko Srdanov, Dako North America, Carpinteria, CA; Manish R. Patel, Florida Cancer Specialists & Research Institute, Sarasota, FL; Ding Wang, Henry Ford Hospital, Detroit, MI; Anthony E. Mega, The Warren Alpert Medical School at Brown University; Howard Safran, The Miriam Hospital, Providence; Howard Safran, Newport Hospital, Newport, RI; Carolyn D. Britten, Medical University of South Carolina, Charleston, SC; Alain Ravaud, CHU de Bordeaux, Bordeaux, France; Thomas E. Stinchcombe, Duke University Medical Center, Durham, NC; Arnold B. Gelb and Kevin Chin, EMD Serono, Billerica, MA; and Michael Schlichting, Merck, Darmstadt, Germany.
authors.forename: Alain
authors.initials: A
authors.lastname: Ravaud
authors.affiliation: Andrea B. Apolo and James L. Gulley, National Institutes of Health, Bethesda, MD; Jeffrey R. Infante, Sarah Cannon Research Institute/Tennessee Oncology, Nashville, TN; Ani Balmanoukian, The Angeles Clinic & Research Institute; Alain C. Mita, Cedars Sinai Medical Center, Los Angeles; Karen Kelly, University of California-Davis, Sacramento; Marko Srdanov, Dako North America, Carpinteria, CA; Manish R. Patel, Florida Cancer Specialists & Research Institute, Sarasota, FL; Ding Wang, Henry Ford Hospital, Detroit, MI; Anthony E. Mega, The Warren Alpert Medical School at Brown University; Howard Safran, The Miriam Hospital, Providence; Howard Safran, Newport Hospital, Newport, RI; Carolyn D. Britten, Medical University of South Carolina, Charleston, SC; Alain Ravaud, CHU de Bordeaux, Bordeaux, France; Thomas E. Stinchcombe, Duke University Medical Center, Durham, NC; Arnold B. Gelb and Kevin Chin, EMD Serono, Billerica, MA; and Michael Schlichting, Merck, Darmstadt, Germany.
authors.forename: Alain C
authors.initials: AC
authors.lastname: Mita
authors.affiliation: Andrea B. Apolo and James L. Gulley, National Institutes of Health, Bethesda, MD; Jeffrey R. Infante, Sarah Cannon Research Institute/Tennessee Oncology, Nashville, TN; Ani Balmanoukian, The Angeles Clinic & Research Institute; Alain C. Mita, Cedars Sinai Medical Center, Los Angeles; Karen Kelly, University of California-Davis, Sacramento; Marko Srdanov, Dako North America, Carpinteria, CA; Manish R. Patel, Florida Cancer Specialists & Research Institute, Sarasota, FL; Ding Wang, Henry Ford Hospital, Detroit, MI; Anthony E. Mega, The Warren Alpert Medical School at Brown University; Howard Safran, The Miriam Hospital, Providence; Howard Safran, Newport Hospital, Newport, RI; Carolyn D. Britten, Medical University of South Carolina, Charleston, SC; Alain Ravaud, CHU de Bordeaux, Bordeaux, France; Thomas E. Stinchcombe, Duke University Medical Center, Durham, NC; Arnold B. Gelb and Kevin Chin, EMD Serono, Billerica, MA; and Michael Schlichting, Merck, Darmstadt, Germany.
authors.forename: Howard
authors.initials: H
authors.lastname: Safran
authors.affiliation: Andrea B. Apolo and James L. Gulley, National Institutes of Health, Bethesda, MD; Jeffrey R. Infante, Sarah Cannon Research Institute/Tennessee Oncology, Nashville, TN; Ani Balmanoukian, The Angeles Clinic & Research Institute; Alain C. Mita, Cedars Sinai Medical Center, Los Angeles; Karen Kelly, University of California-Davis, Sacramento; Marko Srdanov, Dako North America, Carpinteria, CA; Manish R. Patel, Florida Cancer Specialists & Research Institute, Sarasota, FL; Ding Wang, Henry Ford Hospital, Detroit, MI; Anthony E. Mega, The Warren Alpert Medical School at Brown University; Howard Safran, The Miriam Hospital, Providence; Howard Safran, Newport Hospital, Newport, RI; Carolyn D. Britten, Medical University of South Carolina, Charleston, SC; Alain Ravaud, CHU de Bordeaux, Bordeaux, France; Thomas E. Stinchcombe, Duke University Medical Center, Durham, NC; Arnold B. Gelb and Kevin Chin, EMD Serono, Billerica, MA; and Michael Schlichting, Merck, Darmstadt, Germany.
authors.forename: Thomas E
authors.initials: TE
authors.lastname: Stinchcombe
authors.affiliation: Andrea B. Apolo and James L. Gulley, National Institutes of Health, Bethesda, MD; Jeffrey R. Infante, Sarah Cannon Research Institute/Tennessee Oncology, Nashville, TN; Ani Balmanoukian, The Angeles Clinic & Research Institute; Alain C. Mita, Cedars Sinai Medical Center, Los Angeles; Karen Kelly, University of California-Davis, Sacramento; Marko Srdanov, Dako North America, Carpinteria, CA; Manish R. Patel, Florida Cancer Specialists & Research Institute, Sarasota, FL; Ding Wang, Henry Ford Hospital, Detroit, MI; Anthony E. Mega, The Warren Alpert Medical School at Brown University; Howard Safran, The Miriam Hospital, Providence; Howard Safran, Newport Hospital, Newport, RI; Carolyn D. Britten, Medical University of South Carolina, Charleston, SC; Alain Ravaud, CHU de Bordeaux, Bordeaux, France; Thomas E. Stinchcombe, Duke University Medical Center, Durham, NC; Arnold B. Gelb and Kevin Chin, EMD Serono, Billerica, MA; and Michael Schlichting, Merck, Darmstadt, Germany.
authors.forename: Marko
authors.initials: M
authors.lastname: Srdanov
authors.affiliation: Andrea B. Apolo and James L. Gulley, National Institutes of Health, Bethesda, MD; Jeffrey R. Infante, Sarah Cannon Research Institute/Tennessee Oncology, Nashville, TN; Ani Balmanoukian, The Angeles Clinic & Research Institute; Alain C. Mita, Cedars Sinai Medical Center, Los Angeles; Karen Kelly, University of California-Davis, Sacramento; Marko Srdanov, Dako North America, Carpinteria, CA; Manish R. Patel, Florida Cancer Specialists & Research Institute, Sarasota, FL; Ding Wang, Henry Ford Hospital, Detroit, MI; Anthony E. Mega, The Warren Alpert Medical School at Brown University; Howard Safran, The Miriam Hospital, Providence; Howard Safran, Newport Hospital, Newport, RI; Carolyn D. Britten, Medical University of South Carolina, Charleston, SC; Alain Ravaud, CHU de Bordeaux, Bordeaux, France; Thomas E. Stinchcombe, Duke University Medical Center, Durham, NC; Arnold B. Gelb and Kevin Chin, EMD Serono, Billerica, MA; and Michael Schlichting, Merck, Darmstadt, Germany.
authors.forename: Arnold B
authors.initials: AB
authors.lastname: Gelb
authors.affiliation: Andrea B. Apolo and James L. Gulley, National Institutes of Health, Bethesda, MD; Jeffrey R. Infante, Sarah Cannon Research Institute/Tennessee Oncology, Nashville, TN; Ani Balmanoukian, The Angeles Clinic & Research Institute; Alain C. Mita, Cedars Sinai Medical Center, Los Angeles; Karen Kelly, University of California-Davis, Sacramento; Marko Srdanov, Dako North America, Carpinteria, CA; Manish R. Patel, Florida Cancer Specialists & Research Institute, Sarasota, FL; Ding Wang, Henry Ford Hospital, Detroit, MI; Anthony E. Mega, The Warren Alpert Medical School at Brown University; Howard Safran, The Miriam Hospital, Providence; Howard Safran, Newport Hospital, Newport, RI; Carolyn D. Britten, Medical University of South Carolina, Charleston, SC; Alain Ravaud, CHU de Bordeaux, Bordeaux, France; Thomas E. Stinchcombe, Duke University Medical Center, Durham, NC; Arnold B. Gelb and Kevin Chin, EMD Serono, Billerica, MA; and Michael Schlichting, Merck, Darmstadt, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Schlichting
authors.affiliation: Andrea B. Apolo and James L. Gulley, National Institutes of Health, Bethesda, MD; Jeffrey R. Infante, Sarah Cannon Research Institute/Tennessee Oncology, Nashville, TN; Ani Balmanoukian, The Angeles Clinic & Research Institute; Alain C. Mita, Cedars Sinai Medical Center, Los Angeles; Karen Kelly, University of California-Davis, Sacramento; Marko Srdanov, Dako North America, Carpinteria, CA; Manish R. Patel, Florida Cancer Specialists & Research Institute, Sarasota, FL; Ding Wang, Henry Ford Hospital, Detroit, MI; Anthony E. Mega, The Warren Alpert Medical School at Brown University; Howard Safran, The Miriam Hospital, Providence; Howard Safran, Newport Hospital, Newport, RI; Carolyn D. Britten, Medical University of South Carolina, Charleston, SC; Alain Ravaud, CHU de Bordeaux, Bordeaux, France; Thomas E. Stinchcombe, Duke University Medical Center, Durham, NC; Arnold B. Gelb and Kevin Chin, EMD Serono, Billerica, MA; and Michael Schlichting, Merck, Darmstadt, Germany.
authors.forename: Kevin
authors.initials: K
authors.lastname: Chin
authors.affiliation: Andrea B. Apolo and James L. Gulley, National Institutes of Health, Bethesda, MD; Jeffrey R. Infante, Sarah Cannon Research Institute/Tennessee Oncology, Nashville, TN; Ani Balmanoukian, The Angeles Clinic & Research Institute; Alain C. Mita, Cedars Sinai Medical Center, Los Angeles; Karen Kelly, University of California-Davis, Sacramento; Marko Srdanov, Dako North America, Carpinteria, CA; Manish R. Patel, Florida Cancer Specialists & Research Institute, Sarasota, FL; Ding Wang, Henry Ford Hospital, Detroit, MI; Anthony E. Mega, The Warren Alpert Medical School at Brown University; Howard Safran, The Miriam Hospital, Providence; Howard Safran, Newport Hospital, Newport, RI; Carolyn D. Britten, Medical University of South Carolina, Charleston, SC; Alain Ravaud, CHU de Bordeaux, Bordeaux, France; Thomas E. Stinchcombe, Duke University Medical Center, Durham, NC; Arnold B. Gelb and Kevin Chin, EMD Serono, Billerica, MA; and Michael Schlichting, Merck, Darmstadt, Germany.
authors.forename: James L
authors.initials: JL
authors.lastname: Gulley
mesh_terms: D000368:Aged; D000911:Antibodies, Monoclonal / Q000008:administration & dosage* / Q000009:adverse effects; D061067:Antibodies, Monoclonal, Humanized; D015331:Cohort Studies; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D016896:Treatment Outcome; D014571:Urologic Neoplasms / Q000188:drug therapy* / Q000276:immunology
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; C000609138:avelumab