Clinical trial NCT01772004: Avelumab in Metastatic or Locally Advanced Solid Tumors (JAVELIN Solid Tumor)
Official title: A Phase I, Open-label, Multiple-ascending Dose Trial to Investigate the Safety, Tolerability, Pharmacokinetics, Biological and Clinical Activity of Avelumab (MSB0010718C) in Subjects With Metastatic or Locally Advanced Solid Tumors and Expansion to Selected Indications
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Solid Tumors
Keywords: Solid Tumors
MSB0010718C
Phase 1
Pharmacokinetic
anti PD-L1
Non-small cell lung cancer (NSCLC)
Metastatic breast cancer (MBC)
Gastric and gastroesophageal junction (GEJ) cancer
Ovarian cancer
Colorectal cancer (CRC)
Castrate-resistant prostate cancer (CRPC)
Melanoma
Urothelial carcinoma
Bladder cancer
Head and neck squamous cell carcinoma (HNSCC)
Renal cell carcinoma (RCC)
Adrenocortical carcinoma (ACC)
Lead sponsor: EMD Serono
Sponsor class: INDUSTRY
Collaborators: name: Merck KGaA, Darmstadt, Germany
First posted: 2013-01-21
Enrollment: 1756
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

Brief summary: This is a Phase 1, open-label, dose-escalation trial of avelumab \[antibody targeting programmed death ligand 1 (anti PD-L1)\] with consecutive parallel group expansion in participants with selected tumor indications. New recruitment is open for all active cohorts.

Active cohorts: Escalation revised dosing regimen cohort.

Closed cohorts: Non-small cell lung cancer (NSCLC, first line), NSCLC (post-platinum), metastatic breast cancer (MBC), colorectal cancer (CRC), urothelial carcinoma (secondary), mesothelioma, gastric/GEJ cancer (first line switch maintenance and second line), and ovarian cancer (secondary and platinum refractory + liposomal doxorubicin), renal cell carcinoma (second line) melanoma and head, neck squamous cell carcinoma (HNSCC), castrate-resistant prostate cancer (CRPC), adrenocortical carcinoma (ACC) urothelial carcinoma (efficacy), gastric/gastroesophageal junction (GEJ) cancer (third line), renal cell carcinoma (RCC, first line) and escalation phase .


Eligibility criteria: Inclusion Criteria for dose escalation and expansion phase:

* Signed written informed consent
* Male or female participants aged greater than or equal to 18 years
* Participants must have histologically or cytologically proven metastatic or locally advanced solid tumors, for which no standard therapy exists or standard therapy has failed. Availability of tumor archival material or fresh biopsies is optional for participants in dose escalation
* Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1 at trial entry and an estimated life expectancy of at least 3 months
* Disease must be measurable with at least 1 uni-dimensional measurable lesion by RECIST 1.1, except for participants with metastatic castrate-resistant prostate cancer (mCRPC) or metastatic breast cancer (MBC) who may be enrolled with objective evidence of disease without a measureable lesion
* Adequate hematological, hepatic and renal function as defined in the protocol
* Effective contraception for both male and female participants if the risk of conception exists
* Other protocol defined inclusion criteria could apply

Inclusion Criteria for expansion phase:

* Participants must have relapsed, refractory, or progressive disease following last line of treatment (with the exception of the gastric and gastroesophageal junction (GEJ) cancer cohort, which does not require progression). Availability of tumor archival material or fresh biopsies (excluding bone biopsies) is mandatory for eligibility in the expansion cohorts. For participants in the MBC cohort, the biopsy or surgical specimen must have been collected within 90 days prior to the first investigational medicinal product (IMP) administration. Specifically, the following will be required:
* NSCLC post platinum doublet: Histologically or cytologically confirmed stage IIIB or stage IV NSCLC that has progressed after 1 line of platinum-containing doublet chemotherapy. Participants should have received only 1 line of platinum-containing treatment for metastatic disease (i.e., adjuvant treatment with a platinum-containing regimen is not sufficient for eligibility because not received in the context of a metastatic disease). Participants in the NSCLC cohort will only be enrolled in USA
* NSCLC first line: Stage IV (per 7th International Association for the Study of Lung Cancer \[IASLC\] classification) or recurrent NSCLC that is histologically proven. Participants must not have received treatment for their metastatic or recurrent disease. No activating epidermal growth factor receptor (EGFR) mutation nor ALK translocation/re-arrangement
* Gastric and GEJ cancer: Histologically confirmed, unresectable locally advanced or metastatic adenocarcinoma of the gastric and gastro-esophageal junction, treated with first-line chemotherapy combination with or without disease progression. Participants should have received no more than 1 line of treatment for metastatic disease. Participants should not have been treated with trastuzumab (but can be Human Epidermal growth factor Receptor 2 \[HER2\] positive). Participants who received any platinum containing doublet or triplet as a neoadjuvant chemotherapy strategy, but are not ultimately candidates for surgery will also be eligible, as long as they did not have progressive disease after completion of the neoadjuvant chemotherapy. In addition, participants with gastric cancer can enter in the study if their white blood cell (WBC) and lymphocyte count is as defined in the protocol
* MBC: Participants must have histologically confirmed locally advanced or MBC and have tumor that is refractory to or progressive after standard of care therapy. Participants must have received no more than 3 prior lines of cytotoxic therapy for metastatic disease. Participants must have received a taxane and an anthracycline, unless contra-indicated
* Secondary expansion cohorts: Metastatic colorectal cancer (mCRC), Metastatic castrate-resistant prostate cancer (mCRPC), melanoma, ovarian cancer, ACC, mesothelioma, urothelial carcinoma and renal cell carcinoma as defined in the protocol
* Efficacy expansion cohorts: Gastric and GEJ cancer (third line), ovarian cancer (platinum Refractory + liposomal doxorubicin), urothelial carcinoma, and HNSCC as defined in the protocol

  * Other protocol defined inclusion criteria for expansion phase could apply

Exclusion Criteria for dose escalation and expansion phase:

* Concurrent treatment with a non-permitted drug
* Prior therapy with specific antibody/drug targeting T cell co-regulatory proteins (immune checkpoints)
* Concurrent anticancer treatment, major surgery, or use of any investigational drug within 28 days before the start of trial treatment; or concurrent systemic therapy with immunosuppressive agents, use of hormonal agents within 7 days before the start of trial treatment as defined in the protocol. Note: Participants receiving bisphosphonate or denosumab are eligible provided treatment was initiated at least 14 days before the first dose of avelumab.
* Previous malignant disease other than the target malignancy to be investigated in this trial within the last 5 years with the exception of basal or squamous cell carcinoma of the skin or cervical carcinoma in situ
* Rapidly progressive disease (for example, tumor lysis syndrome)
* Active or history of central nervous system metastases
* Receipt of any organ transplantation including allogeneic stem-cell transplantation
* Significant acute or chronic infections as defined in the protocol
* Active or history of any autoimmune disease (Participants with diabetes Type 1, vitiligo, psoriasis, hypo- or hyperthyroid disease not requiring immunosuppressive treatment are eligible) or immunodeficiencies
* Known severe hypersensitivity reactions to monoclonal antibodies, any history of anaphylaxis, or uncontrolled asthma
* Persisting toxicity related to prior therapy greater than Grade 1 NCI-CTCAE v4.0, however sensory neuropathy less than or equal to Grade 2 is acceptable
* Pregnancy or lactation period
* Known alcohol or drug abuse
* Clinically significant (that is, active) cardiovascular disease
* All other significant diseases (for example, inflammatory bowel disease), which, in the opinion of the investigator, might impair the Participant's tolerance of trial treatment
* Any psychiatric condition that would prohibit the understanding or rendering of informed consent
* Legal incapacity or limited legal capacity
* Non-oncology vaccine therapies for prevention of infection disease (for example, seasonal flu vaccine, human papilloma virus vaccine) within 4 weeks of study drug administration. Vaccination while on study is also prohibited except for administration of the inactivated influenza vaccine

Primary outcomes:
measure: Dose Escalation Cohort (Excluding Once Weekly Avelumab 10 mg/kg Cohort): Number of Participants Experiencing Dose Limiting Toxicities (DLTs)
timeFrame: Dose Escalation: Baseline up to Week 3
measure: Efficacy Expansion Cohort (Ovarian Cancer): Number of Participants With Confirmed Best Overall Response (BOR) as Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1), as Adjudicated by Independent Endpoint Review Committee (IERC)
timeFrame: Ovarian Cancer Efficacy Expansion: Baseline up to Day 620
measure: Efficacy Expansion Cohort(Urothelial Carcinoma): Number of Participants With Confirmed Best Overall Response (BOR) as Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1), as Adjudicated by Independent Endpoint Review Committee (IERC)
timeFrame: Urothelial Carcinoma Efficacy Expansion: Baseline up to Day 931
measure: Efficacy Expansion Cohort (GC/GEJC, Third Line): Number of Participants With Confirmed Best Overall Response (BOR) as Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1), as Adjudicated by Independent Endpoint Review Committee (IERC)
timeFrame: GC/GEJC, Third Line Efficacy Expansion: Baseline up to Day 871
measure: Efficacy Expansion Cohort (HNSCC): Number of Participants With Confirmed Best Overall Response (BOR) as Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1), as Adjudicated by Independent Endpoint Review Committee (IERC)
timeFrame: HNSCC Efficacy Expansion: Baseline up to Day 1072
Secondary outcomes:
measure: Dose Escalation and Expansion Cohorts: Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and TEAEs as Per Severity
timeFrame: Up to Day 2511
measure: Dose Escalation and Expansion Cohorts: Number of Participants With Treatment-Related Treatment-Emergent Adverse Events (TEAEs) and Treatment-Related TEAEs as Per Severity
timeFrame: Baseline up to Day 2511
measure: Dose Escalation Cohort (Excluding Once Weekly Avelumab 10 mg/kg Cohort): Area Under Serum Concentration-Time Curve From the Time of Dosing to the Time of the Last Observation (AUC0-t) of Avelumab
timeFrame: Pre-infusion, at end of 1-hour infusion (Day 1), 0.5, 1, 2, 4, 6,12, 24, 36, 48 hours after end of infusion
measure: Dose Escalation Cohort (Excluding Once Weekly Avelumab 10 mg/kg Cohort): Area Under the Serum Concentration-Time Curve From Time Zero to Infinity (AUC0-infinity) of Avelumab
timeFrame: Pre-infusion, at end of 1-hour infusion (Day 1), 0.5, 1, 2, 4, 6,12, 24, 36, 48 hours after end of infusion
measure: Dose Escalation Cohort (Excluding Once Weekly Avelumab 10 mg/kg Cohort): Maximum Observed Serum Concentration (Cmax) of Avelumab
timeFrame: Pre-infusion, at end of 1-hour infusion (Day 1), 0.5, 1, 2, 4, 6,12, 24, 36, 48 hours after end of infusion
measure: Dose Escalation Cohort (Excluding Once Weekly Avelumab 10 mg/kg Cohort): Time to Reach Maximum Observed Serum Concentration (Tmax) of Avelumab
timeFrame: Pre-infusion, at end of 1-hour infusion (Day 1), 0.5, 1, 2, 4, 6,12, 24, 36, 48 hours after end of infusion
measure: Dose Escalation Cohort (Excluding Once Weekly Avelumab 10 mg/kg Cohort): Apparent Terminal Half-Life (t1/2) of Avelumab
timeFrame: Pre-infusion, at end of 1-hour infusion (Day 1), 0.5, 1, 2, 4, 6,12, 24, 36, 48 hours after end of infusion
measure: Dose Expansion Phase: Serum Concentration at End of Infusion (CEOI) of Avelumab
timeFrame: At Day 1, 15, 29, 43, 85, 127 and 169
measure: Dose Expansion Phase: Minimum Serum Post-dose (Ctrough) Concentration of Avelumab
timeFrame: At Day 15, 29, 43, 57, 71, 85, 99, 127 and 169
measure: Dose Escalation Cohort (Excluding Once Weekly Avelumab 10 mg/kg Cohort): Number of Participants With Immune Related Best Overall Response (irBOR) According to Modified Immune-Related Response Criteria (irRC)
timeFrame: Dose Escalation: Baseline up to Day 1023
measure: Dose Expansion Cohort: Number of Participants With Immune Related Best Overall Response (irBOR) According to Modified Immune-Related Response Criteria (irRC)
timeFrame: Dose Expansion: Baseline up to Day 2023
measure: Dose Escalation Cohort: Number of Participants With Best Overall Response (BOR) According to Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1
timeFrame: Dose Escalation: Baseline up to Day 2511
measure: Dose Expansion Cohort: Number of Participants With Best Overall Response (BOR) According to Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1
timeFrame: Dose Expansion: Baseline up to Day 2023
measure: Dose Expansion Cohort (Secondary Urothelial Carcinoma Cohort): Number of Participants With Confirmed Best Overall Response According to Response Evaluation Criteria in Solid Tumors Version 1.1 as Adjudicated by an Independent Endpoint Review Committee
timeFrame: Secondary Urothelial Carcinoma Dose Expansion: Baseline up to Day 931
measure: Dose Expansion Cohort: Progression-Free Survival (PFS) Time According to Response Evaluation Criteria in Solid Tumors Version (RECIST) 1.1
timeFrame: Dose Expansion: Baseline up to Day 2023
measure: Dose Expansion Cohort: Immune Related Progression-Free Survival (irPFS) Time According to Modified Immune-Related Response Criteria (irRC)
timeFrame: Dose Expansion: Baseline up to Day 2023
measure: Dose Expansion Cohort: Overall Survival (OS) Time
timeFrame: Dose Expansion: Baseline up to Day 2023
measure: Dose Escalation Cohort (Excluding Once Weekly Avelumab 10 mg/kg Cohort): Programmed Death Ligand 1 (PD-L1) Receptor Occupancy
timeFrame: Pre-infusion on Day 1; 48 hours after infusion on Day 3; Pre-infusion on Days 15, 43, and 85
measure: Dose Expansion Cohort: Number of Participants With Positive Programmed Death Receptor-1 Ligand-1 (PD-L1) Biomarker Expression in Tumor Tissue
timeFrame: Dose Expansion: Baseline up to Day 2023
measure: Primary Expansion Cohorts: Number of Participants With Unconfirmed Response at Week 13 According to Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1
timeFrame: Week 13
measure: Dose Expansion Cohort: Duration of Response According to Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 Per Investigator Assessment
timeFrame: Dose Expansion: Baseline up to Day 2023
measure: Dose Expansion Cohort: Duration of Response According to Modified Immune-Related Response Criteria (irRC) Per Investigator Assessment
timeFrame: Dose Expansion: Baseline up to Day 2023
measure: Efficacy Expansion Cohorts: Duration of Response According to Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 as Per Independent Endpoint Review Committee (IERC)
timeFrame: Efficacy Expansion: Baseline up to Day 1072
measure: Efficacy Expansion Cohorts: Progression-Free Survival (PFS) Time According to Response Evaluation Criteria in Solid Tumors Version (RECIST) 1.1 as Per Independent Endpoint Review Committee (IERC)
timeFrame: Efficacy Expansion: Baseline up to Day 1072
measure: Dose Escalation Cohort (Excluding Once Weekly Avelumab 10 mg/kg Cohort): Number of Participants With at Least 1 Positive Anti Drug Antibodies (ADA)
timeFrame: Dose Escalation: Baseline up to Day 1023
measure: Dose Expansion Cohort: Number of Participants With Atleast 1 Positive Anti Drug Antibodies (ADA) Assay
timeFrame: Dose Expansion: Baseline up to Day 2023
Other outcomes:
Locations:
city: Goodyear
country: United States
facility: Cancer Treatment Centers of America - Western Regional Medical Center
state: Arizona
city: Scottsdale
country: United States
facility: Scottsdale Healthcare Corporation
state: Arizona
city: Scottsdale
country: United States
facility: Pinnacle Oncology Hematology
state: Arizona
city: Rogers
country: United States
facility: Highlands Oncology Group
state: Arkansas
city: Anaheim
country: United States
facility: Pacific Cancer Medical Center, Inc.
state: California
city: Encinitas
country: United States
facility: California Cancer Associates for Research & Excellence, Inc
state: California
city: Inglewood
country: United States
facility: Healing Hands Oncology and Medical Care
state: California
city: La Jolla
country: United States
facility: Scripps Health dba Scripps Clinical Research Services
state: California
city: Los Angeles
country: United States
facility: The Angeles Clinic and Research Institute - West LA
state: California
city: Los Angeles
country: United States
facility: Cedars-Sinai Medical Center - Oncology
state: California
city: Sacramento
country: United States
facility: University of California Davis Health System
state: California
city: San Diego
country: United States
facility: Sharp Memorial Hospital
state: California
city: Washington
country: United States
facility: Georgetown University Medical Center- Research Parent
state: District of Columbia
city: Fort Lauderdale
country: United States
facility: Holy Cross Hospital
state: Florida
city: Miami
country: United States
facility: University of Miami
state: Florida
city: Port Saint Lucie
country: United States
facility: Hematology - Oncology Associates of Treasure Coast - Hematology-Oncology Associates of Treasure Coast
state: Florida
city: Sarasota
country: United States
facility: Florida Cancer Specialists
state: Florida
city: Athens
country: United States
facility: Northeast Georgia Cancer Care, LLC
state: Georgia
city: Atlanta
country: United States
facility: Peachtree Hematology-Oncology Consultants, PC
state: Georgia
city: Augusta
country: United States
facility: Augusta University - formerly Georgia Regents University
state: Georgia
city: Marietta
country: United States
facility: Northwest Georgia Oncology Centers PC
state: Georgia
city: Chicago
country: United States
facility: University of Chicago Medical Center
state: Illinois
city: Lafayette
country: United States
facility: Horizon Oncology Research, INC
state: Indiana
city: Baltimore
country: United States
facility: The Johns Hopkins Hospital
state: Maryland
city: Bethesda
country: United States
facility: RCCA MD LLC - Bethesda
state: Maryland
city: Bethesda
country: United States
facility: National Cancer Institute
state: Maryland
city: Rockville
country: United States
facility: Maryland Oncology Hematology, P.A.
state: Maryland
city: Detroit
country: United States
facility: Karmanos Cancer Institute
state: Michigan
city: Detroit
country: United States
facility: Henry Ford Medical Center
state: Michigan
city: Lansing
country: United States
facility: Michigan State University
state: Michigan
city: Minneapolis
country: United States
facility: Virginia Piper Cancer Institute
state: Minnesota
city: Kansas City
country: United States
facility: Kansas City Research Institute, LLC - Phase I Unit
state: Missouri
city: Saint Louis
country: United States
facility: Washington University in St. Louis
state: Missouri
city: Farmington
country: United States
facility: San Juan Oncology Associates
state: New Mexico
city: Bronx
country: United States
facility: Montefiore Medical Center PRIME
state: New York
city: New York
country: United States
facility: Columbia University College of Phys & Surgeons
state: New York
city: Chapel Hill
country: United States
facility: University of North Carolina at Chapel Hill
state: North Carolina
city: Huntersville
country: United States
facility: Carolina BioOncology Institute, LLC - Cancer Therapy and Research Center
state: North Carolina
city: Cincinnati
country: United States
facility: UC Health Clinical Trials Office
state: Ohio
city: Cleveland
country: United States
facility: University Hospitals Case Medical Center - Case Comprehensive Cancer Center
state: Ohio
city: Columbus
country: United States
facility: OSU - James Comprehensive Cancer Center - Division of Hematology
state: Ohio
city: Columbus
country: United States
facility: Mid Ohio Oncology Hematology, DBA The Mark H. Zangmeister Center - d/b/a The Mark H. Zangmeister Center
state: Ohio
city: Oklahoma City
country: United States
facility: Oklahoma University Medical Center
state: Oklahoma
city: Hershey
country: United States
facility: Penn State Univ. Milton S. Hershey Medical Center - MSHMC Cardiology
state: Pennsylvania
city: Providence
country: United States
facility: Rhode Island Hospital
state: Rhode Island
city: Charleston
country: United States
facility: Medical University of South Carolina
state: South Carolina
city: Germantown
country: United States
facility: The West Clinic
state: Tennessee
city: Memphis
country: United States
facility: Baptist Cancer Center
state: Tennessee
city: Nashville
country: United States
facility: SCRI - Tennessee Oncology
state: Tennessee
city: Dallas
country: United States
facility: Texas Oncology, P.A
state: Texas
city: Houston
country: United States
facility: Oncology Consultants, P.A.
state: Texas
city: Tyler
country: United States
facility: Texas Oncology, P.A. - Tyler
state: Texas
city: Lakewood
country: United States
facility: Northwest Medical Specialties, PLLC
state: Washington
city: Wilrijk
country: Belgium
facility: GZA Ziekenhuizen - Campus Sint-Augustinus
city: Benesov
country: Czechia
facility: Nemocnice Rudolfa a Stefanie Benesov, a.s.
city: Angers cedex 2
country: France
facility: ICO - Site Paul Papin - service d'oncologie medicale
city: Lyon
country: France
facility: Centre Léon Bérard
city: Nice cedex 02
country: France
facility: Centre Antoine Lacassagne
city: Strasbourg Cedex
country: France
facility: Centre Paul Strauss - Service de Médecine Oncologique
city: Mainz
country: Germany
facility: Universitaetsmedizin der Johannes Gutenberg-Universitaet Mainz - I. Medizinische Klinik Gastroenterologie u Hepato.
city: Villingen-Schwenningen
country: Germany
facility: Schwarzwald-Baar Klinikum Villingen-Schwenningen GmbH - Innere Medizin II Haematologie / Onkologie
city: Seongnam-si
country: Korea, Republic of
facility: Seoul National University Bundang Hospital
city: Seoul
country: Korea, Republic of
facility: Korea University Anam Hospital
city: Seoul
country: Korea, Republic of
facility: Seoul National University Hospital
city: Seoul
country: Korea, Republic of
facility: Severance Hospital, Yonsei University
city: Seoul
country: Korea, Republic of
facility: Asan Medical Center
city: Seoul
country: Korea, Republic of
facility: Gangnam Severance Hospital, Yonsei University Health System
city: Seoul
country: Korea, Republic of
facility: Samsung Medical Center
city: Seoul
country: Korea, Republic of
facility: The Catholic University of Korea, Seoul St. Mary's Hospital
city: Warszawa
country: Poland
facility: Centrum Onkologii-Instytut im. M. Sklodowskiej Curie - Dept of Digestive System Oncology
city: Tainan
country: Taiwan
facility: National Cheng Kung University Hospital
city: Taipei
country: Taiwan
facility: National Taiwan University Hospital
city: London
country: United Kingdom
facility: Sarah Cannon Research Institute UK
city: Plymouth
country: United Kingdom
facility: Derriford Hospital - Dept of Oncology Clinical Trials
Study officials:
affiliation: EMD Serono Inc., an affiliate of Merck KGaA, Darmstadt, Germany
name: Medical Responsible
role: STUDY_DIRECTOR
References:
citation: Apolo AB, Infante JR, Balmanoukian A, Patel MR, Wang D, Kelly K, Mega AE, Britten CD, Ravaud A, Mita AC, Safran H, Stinchcombe TE, Srdanov M, Gelb AB, Schlichting M, Chin K, Gulley JL. Avelumab, an Anti-Programmed Death-Ligand 1 Antibody, In Patients With Refractory Metastatic Urothelial Carcinoma: Results From a Multicenter, Phase Ib Study. J Clin Oncol. 2017 Jul 1;35(19):2117-2124. doi: 10.1200/JCO.2016.71.6795. Epub 2017 Apr 4.
citation: Gulley JL, Rajan A, Spigel DR, Iannotti N, Chandler J, Wong DJL, Leach J, Edenfield WJ, Wang D, Grote HJ, Heydebreck AV, Chin K, Cuillerot JM, Kelly K. Avelumab for patients with previously treated metastatic or recurrent non-small-cell lung cancer (JAVELIN Solid Tumor): dose-expansion cohort of a multicentre, open-label, phase 1b trial. Lancet Oncol. 2017 May;18(5):599-610. doi: 10.1016/S1470-2045(17)30240-1. Epub 2017 Mar 31.
citation: Heery CR, O'Sullivan-Coyne G, Madan RA, Cordes L, Rajan A, Rauckhorst M, Lamping E, Oyelakin I, Marte JL, Lepone LM, Donahue RN, Grenga I, Cuillerot JM, Neuteboom B, Heydebreck AV, Chin K, Schlom J, Gulley JL. Avelumab for metastatic or locally advanced previously treated solid tumours (JAVELIN Solid Tumor): a phase 1a, multicohort, dose-escalation trial. Lancet Oncol. 2017 May;18(5):587-598. doi: 10.1016/S1470-2045(17)30239-5. Epub 2017 Mar 31.
citation: Guigay J, Lee KW, Patel MR, Daste A, Wong DJ, Goel S, Gordon MS, Gutierrez M, Balmanoukian A, Le Tourneau C, Mita A, Vansteene D, Keilholz U, Schoffski P, Grote HJ, Zhou D, Bajars M, Penel N. Avelumab for platinum-ineligible/refractory recurrent and/or metastatic squamous cell carcinoma of the head and neck: phase Ib results from the JAVELIN Solid Tumor trial. J Immunother Cancer. 2021 Oct;9(10):e002998. doi: 10.1136/jitc-2021-002998.
citation: Kelly K, Manitz J, Patel MR, D'Angelo SP, Apolo AB, Rajan A, Kasturi V, Speit I, Bajars M, Warth J, Gulley JL. Efficacy and immune-related adverse event associations in avelumab-treated patients. J Immunother Cancer. 2020 Nov;8(2):e001427. doi: 10.1136/jitc-2020-001427.
citation: Verschraegen CF, Jerusalem G, McClay EF, Iannotti N, Redfern CH, Bennouna J, Chen FL, Kelly K, Mehnert J, Morris JC, Taylor M, Spigel D, Wang D, Grote HJ, Zhou D, Munshi N, Bajars M, Gulley JL. Efficacy and safety of first-line avelumab in patients with advanced non-small cell lung cancer: results from a phase Ib cohort of the JAVELIN Solid Tumor study. J Immunother Cancer. 2020 Sep;8(2):e001064. doi: 10.1136/jitc-2020-001064.
citation: Del Rivero J, Donahue RN, Marte JL, Gramza AW, Bilusic M, Rauckhorst M, Cordes L, Merino MJ, Dahut WL, Schlom J, Gulley JL, Madan RA. A Case Report of Sequential Use of a Yeast-CEA Therapeutic Cancer Vaccine and Anti-PD-L1 Inhibitor in Metastatic Medullary Thyroid Cancer. Front Endocrinol (Lausanne). 2020 Aug 7;11:490. doi: 10.3389/fendo.2020.00490. eCollection 2020.
citation: Vaishampayan U, Schoffski P, Ravaud A, Borel C, Peguero J, Chaves J, Morris JC, Kotecki N, Smakal M, Zhou D, Guenther S, Bajars M, Gulley JL. Avelumab monotherapy as first-line or second-line treatment in patients with metastatic renal cell carcinoma: phase Ib results from the JAVELIN Solid Tumor trial. J Immunother Cancer. 2019 Oct 24;7(1):275. doi: 10.1186/s40425-019-0746-2.
citation: Rajan A, Heery CR, Thomas A, Mammen AL, Perry S, O'Sullivan Coyne G, Guha U, Berman A, Szabo E, Madan RA, Ballester LY, Pittaluga S, Donahue RN, Tsai YT, Lepone LM, Chin K, Ginty F, Sood A, Hewitt SM, Schlom J, Hassan R, Gulley JL. Efficacy and tolerability of anti-programmed death-ligand 1 (PD-L1) antibody (Avelumab) treatment in advanced thymoma. J Immunother Cancer. 2019 Oct 21;7(1):269. doi: 10.1186/s40425-019-0723-9.
citation: Novakovic AM, Wilkins JJ, Dai H, Wade JR, Neuteboom B, Brar S, Bello CL, Girard P, Khandelwal A. Changing Body Weight-Based Dosing to a Flat Dose for Avelumab in Metastatic Merkel Cell and Advanced Urothelial Carcinoma. Clin Pharmacol Ther. 2020 Mar;107(3):588-596. doi: 10.1002/cpt.1645. Epub 2019 Nov 18.
citation: Chung HC, Arkenau HT, Lee J, Rha SY, Oh DY, Wyrwicz L, Kang YK, Lee KW, Infante JR, Lee SS, Kemeny M, Keilholz U, Melichar B, Mita A, Plummer R, Smith D, Gelb AB, Xiong H, Hong J, Chand V, Safran H. Avelumab (anti-PD-L1) as first-line switch-maintenance or second-line therapy in patients with advanced gastric or gastroesophageal junction cancer: phase 1b results from the JAVELIN Solid Tumor trial. J Immunother Cancer. 2019 Feb 4;7(1):30. doi: 10.1186/s40425-019-0508-1.
citation: Disis ML, Taylor MH, Kelly K, Beck JT, Gordon M, Moore KM, Patel MR, Chaves J, Park H, Mita AC, Hamilton EP, Annunziata CM, Grote HJ, von Heydebreck A, Grewal J, Chand V, Gulley JL. Efficacy and Safety of Avelumab for Patients With Recurrent or Refractory Ovarian Cancer: Phase 1b Results From the JAVELIN Solid Tumor Trial. JAMA Oncol. 2019 Mar 1;5(3):393-401. doi: 10.1001/jamaoncol.2018.6258.
citation: Keilholz U, Mehnert JM, Bauer S, Bourgeois H, Patel MR, Gravenor D, Nemunaitis JJ, Taylor MH, Wyrwicz L, Lee KW, Kasturi V, Chin K, von Heydebreck A, Gulley JL. Avelumab in patients with previously treated metastatic melanoma: phase 1b results from the JAVELIN Solid Tumor trial. J Immunother Cancer. 2019 Jan 16;7(1):12. doi: 10.1186/s40425-018-0459-y.
citation: Hassan R, Thomas A, Nemunaitis JJ, Patel MR, Bennouna J, Chen FL, Delord JP, Dowlati A, Kochuparambil ST, Taylor MH, Powderly JD, Vaishampayan UN, Verschraegen C, Grote HJ, von Heydebreck A, Chin K, Gulley JL. Efficacy and Safety of Avelumab Treatment in Patients With Advanced Unresectable Mesothelioma: Phase 1b Results From the JAVELIN Solid Tumor Trial. JAMA Oncol. 2019 Mar 1;5(3):351-357. doi: 10.1001/jamaoncol.2018.5428.
citation: Le Tourneau C, Hoimes C, Zarwan C, Wong DJ, Bauer S, Claus R, Wermke M, Hariharan S, von Heydebreck A, Kasturi V, Chand V, Gulley JL. Avelumab in patients with previously treated metastatic adrenocortical carcinoma: phase 1b results from the JAVELIN solid tumor trial. J Immunother Cancer. 2018 Oct 22;6(1):111. doi: 10.1186/s40425-018-0424-9.
citation: Patel MR, Ellerton J, Infante JR, Agrawal M, Gordon M, Aljumaily R, Britten CD, Dirix L, Lee KW, Taylor M, Schoffski P, Wang D, Ravaud A, Gelb AB, Xiong J, Rosen G, Gulley JL, Apolo AB. Avelumab in metastatic urothelial carcinoma after platinum failure (JAVELIN Solid Tumor): pooled results from two expansion cohorts of an open-label, phase 1 trial. Lancet Oncol. 2018 Jan;19(1):51-64. doi: 10.1016/S1470-2045(17)30900-2. Epub 2017 Dec 5.
citation: Donahue RN, Lepone LM, Grenga I, Jochems C, Fantini M, Madan RA, Heery CR, Gulley JL, Schlom J. Analyses of the peripheral immunome following multiple administrations of avelumab, a human IgG1 anti-PD-L1 monoclonal antibody. J Immunother Cancer. 2017 Feb 21;5:20. doi: 10.1186/s40425-017-0220-y. eCollection 2017.