Avelumab in Metastatic or Locally Advanced Solid Tumors (JAVELIN Solid Tumor)

NCT01772004 | Completed Phase 1 Results DMC

• 2 other identifiers: EMR 100070-0012013-002834-19
• Study Type: interventional
• Target: 1,756
• Locations: 9 countries
• Sites: 74

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 .

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)

Outcome Measures

Primary Outcomes (5)

• Dose Escalation Cohort (Excluding Once Weekly Avelumab 10 mg/kg Cohort): Number of Participants Experiencing Dose Limiting Toxicities (DLTs)

  DLT: defined using National Cancer Institute Common Toxicity Criteria for Adverse Events Version 4.0, as any one of following: any Grade (Gr) \>=3toxicity that is possibly/probably/ definitely related to avelumab, except for any of following: Gr 3 infusion-related reaction resolving within 6 hours and controlled with medical management, Transient Gr 3 flu-like symptoms/fever, which is controlled with medical management, Transient Gr 3 fatigue, local reactions, headache, nausea, emesis that resolves to \<= Gr 1, Gr3 diarrhea, Gr 3 skin toxicity, Gr 3 liver function test increase that resolves to \<= Gr1 in \< 7 days after medical management has been initiated, Single laboratory values out of normal range that were unlikely related to study treatment according to investigator, did not have any clinical correlate, and resolved to \<= Gr1 within 7 days with adequate medical management and tumor flare phenomenon defined as local pain, irritation/rash localized at sites of known/suspected tumor.

  Dose Escalation: Baseline up to Week 3

• 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)

  Confirmed BOR was determined according to RECIST 1.1 and as adjudicated by an Independent Endpoint Review Committee (IERC) and defined as best response of any of complete response (CR), partial response (PR), stable disease (SD) and progressive disease (PD) recorded from date of randomization until disease progression/recurrence (taking smallest measurement recorded since start of treatment as reference). CR: Disappearance of all evidence of target/non-target lesions. PR: At least 30%reduction from baseline in sum of longest diameter (SLD) of all lesions. SD: Neither sufficient increase to qualify for PD nor sufficient shrinkage to qualify for PR. PD: at least a 20% increase in SLD, taking as reference smallest SLD recorded from baseline/appearance of 1or more new lesions and unequivocal progression of non-target lesions.

  Ovarian Cancer Efficacy Expansion: Baseline up to Day 620

• 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)

  Confirmed BOR was determined according to RECIST 1.1 and as adjudicated by an Independent Endpoint Review Committee (IERC) and defined as best response of any of complete response (CR), partial response (PR), stable disease (SD) and progressive disease (PD) recorded from date of randomization until disease progression/recurrence (taking smallest measurement recorded since start of treatment as reference). CR: Disappearance of all evidence of target/non-target lesions. PR: At least 30% reduction from baseline in sum of longest diameter (SLD) of all lesions. SD: Neither sufficient increase to qualify for PD nor sufficient shrinkage to qualify for PR. PD: at least a 20% increase in SLD, taking as reference smallest SLD recorded from baseline/appearance of 1 or more new lesions and unequivocal progression of non-target lesions.

  Urothelial Carcinoma Efficacy Expansion: Baseline up to Day 931

• 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)

  Confirmed BOR was determined according to RECIST 1.1 and as adjudicated by an Independent Endpoint Review Committee (IERC) and defined as best response of any of complete response (CR), partial response (PR), stable disease (SD) and progressive disease (PD) recorded from date of randomization until disease progression/recurrence (taking smallest measurement recorded since start of treatment as reference). CR: Disappearance of all evidence of target/non-target lesions. PR: At least 30% reduction from baseline in sum of longest diameter (SLD) of all lesions. SD: Neither sufficient increase to qualify for PD nor sufficient shrinkage to qualify for PR. PD: at least a 20% increase in SLD, taking as reference smallest SLD recorded from baseline/appearance of 1 or more new lesions and unequivocal progression of non-target lesions.

  GC/GEJC, Third Line Efficacy Expansion: Baseline up to Day 871

• 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)

  Confirmed BOR was determined according to RECIST 1.1 and as adjudicated by an Independent Endpoint Review Committee (IERC) and defined as best response of any of complete response (CR), partial response (PR), stable disease (SD) and progressive disease (PD) recorded from date of randomization until disease progression/recurrence (taking smallest measurement recorded since start of treatment as reference). CR: Disappearance of all evidence of target/non-target lesions. PR: At least 30%reduction from baseline in sum of longest diameter (SLD) of all lesions. SD: Neither sufficient increase to qualify for PD nor sufficient shrinkage to qualify for PR. PD: at least a 20% increase in SLD, taking as reference smallest SLD recorded from baseline/appearance of 1or more new lesions and unequivocal progression of non-target lesions.

  HNSCC Efficacy Expansion: Baseline up to Day 1072

Secondary Outcomes (26)

• Dose Escalation and Expansion Cohorts: Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and TEAEs as Per Severity

  Up to Day 2511

• Dose Escalation and Expansion Cohorts: Number of Participants With Treatment-Related Treatment-Emergent Adverse Events (TEAEs) and Treatment-Related TEAEs as Per Severity

  Baseline up to Day 2511

• 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

  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

• 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

  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

• Dose Escalation Cohort (Excluding Once Weekly Avelumab 10 mg/kg Cohort): Maximum Observed Serum Concentration (Cmax) of Avelumab

  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

Study Arms (23)

Dose Escalation Cohort: Avelumab 1.0 mg/kg

EXPERIMENTAL

Participants with metastatic or locally advanced solid tumors received intravenous infusion of Avelumab at a dose of 1.0 milligrams per kilogram (mg/kg) once every 2 weeks in dose escalation cohort until confirmed progression, unacceptable toxicity, or any reason for withdrawal from the trial or investigational medicinal product (IMP) occurs.

Drug: Avelumab

Dose Escalation Cohort: Avelumab 3.0 mg/kg

EXPERIMENTAL

Participants with metastatic or locally advanced solid tumors received intravenous infusion of Avelumab at a dose of 3.0 mg/kg once every 2 weeks in dose escalation cohort until confirmed progression, unacceptable toxicity, or any reason for withdrawal from the trial or IMP occurs.

Drug: Avelumab

Dose Escalation Cohort: Avelumab 10.0 mg/kg

EXPERIMENTAL

Participants with metastatic or locally advanced solid tumors received intravenous infusion of Avelumab at a dose of 10.0 mg/kg once every 2 weeks in dose escalation cohort until confirmed progression, unacceptable toxicity, or any reason for withdrawal from the trial or IMP occurs.

Drug: Avelumab

Dose Escalation Cohort: Avelumab 20.0 mg/kg

EXPERIMENTAL

Participants with metastatic or locally advanced solid tumors received intravenous infusion of Avelumab at a dose of 20.0 mg/kg once every 2 weeks in dose escalation cohort until confirmed progression, unacceptable toxicity, or any reason for withdrawal from the trial or IMP occurs.

Drug: Avelumab

Dose Escalation Cohort: Avelumab 10.0 mg/kg Weekly

EXPERIMENTAL

Participants with metastatic or locally advanced solid tumors received intravenous infusion of Avelumab at a dose of 10.0 mg/kg once weekly for the first 12 weeks and once every 2 weeks starting Week 13 in dose escalation cohort until confirmed progression, unacceptable toxicity, or any reason for withdrawal from the trial or IMP occurs.

Drug: Avelumab

Primary Expansion Cohort: NSCLC, Post-platinum Doublet

EXPERIMENTAL

Participants with non-small cell lung cancer (NSCLC), who had progressed after 1 line of platinum-containing doublet chemotherapy received intravenous infusion of Avelumab at a dose of 10.0 mg/kg once every 2 weeks in primary expansion cohort until confirmed progression, unacceptable toxicity, or any reason for withdrawal from the trial or IMP occurs.

Drug: Avelumab

Primary Expansion Cohort: NSCLC, First Line

EXPERIMENTAL

Participants with non-small cell lung cancer (NSCLC), first line received intravenous infusion of Avelumab at a dose of 10.0 mg/kg once every 2 weeks in primary expansion cohort until confirmed progression, unacceptable toxicity, or any reason for withdrawal from the trial or IMP occurs.

Drug: Avelumab

Primary Expansion Cohort: Metastatic Breast Cancer

EXPERIMENTAL

Participants with metastatic breast cancer received intravenous infusion of Avelumab at a dose of 10.0 mg/kg once every 2 weeks in primary expansion cohort until confirmed progression, unacceptable toxicity, or any reason for withdrawal from the trial or IMP occurs.

Drug: Avelumab

Primary Expansion Cohort: GC/GEJC Progressed

EXPERIMENTAL

Participants with gastric (GC) and gastroesophageal junction cancer (GEJC) who progressed on or after first line chemotherapy received intravenous infusion of Avelumab at a dose of 10.0 mg/kg once every 2 weeks in primary expansion cohort until confirmed progression, unacceptable toxicity, or any reason for withdrawal from the trial or IMP occurs.

Drug: Avelumab

Primary Expansion Cohort: GC/GEJC Non Progressed

EXPERIMENTAL

Participants with gastric (GC) and gastroesophageal junction cancer (GEJC) who non-progressed on or after first-line chemotherapy received intravenous infusion of Avelumab at a dose of 10.0 mg/kg once every 2 weeks in primary expansion cohort until confirmed progression, unacceptable toxicity, or any reason for withdrawal from the trial or IMP occurs.

Drug: Avelumab

Secondary Expansion Cohort: Colorectal Cancer

EXPERIMENTAL

Participants with colorectal cancer received intravenous infusion of Avelumab at a dose of 10.0 mg/kg once every 2 weeks in secondary expansion cohort until confirmed progression, unacceptable toxicity, or any reason for withdrawal from the trial or IMP occurs.

Drug: Avelumab

Secondary Expansion Cohort: Castrate-resistant Prostate Cancer

EXPERIMENTAL

Participants with castrate-resistant prostate cancer received intravenous infusion of Avelumab at a dose of 10.0 mg/kg once every 2 weeks in secondary expansion cohort until confirmed progression, unacceptable toxicity, or any reason for withdrawal from the trial or IMP occurs.

Drug: Avelumab

Secondary Expansion Cohort: Adrenocortical Carcinoma

EXPERIMENTAL

Participants with adrenocortical carcinoma received intravenous infusion of Avelumab at a dose of 10.0 mg/kg once every 2 weeks in secondary expansion cohort until confirmed progression, unacceptable toxicity, or any reason for withdrawal from the trial or IMP occurs.

Drug: Avelumab

Secondary Expansion Cohort: Melanoma

EXPERIMENTAL

Participants with melanoma received intravenous infusion of Avelumab at a dose of 10.0 mg/kg once every 2 weeks in secondary expansion cohort until confirmed progression, unacceptable toxicity, or any reason for withdrawal from the trial or IMP occurs.

Drug: Avelumab

Secondary Expansion Cohort: Mesothelioma

EXPERIMENTAL

Participants with mesothelioma received intravenous infusion of Avelumab at a dose of 10.0 mg/kg once every 2 weeks in secondary expansion cohort until confirmed progression, unacceptable toxicity, or any reason for withdrawal from the trial or IMP occurs.

Drug: Avelumab

Secondary Expansion Cohort: Urothelial Carcinoma

EXPERIMENTAL

Participants with urothelial carcinoma received intravenous infusion of Avelumab at a dose of 10.0 mg/kg once every 2 weeks in secondary expansion cohort until confirmed progression, unacceptable toxicity, or any reason for withdrawal from the trial or IMP occurs.

Drug: Avelumab

Secondary Expansion Cohort: Ovarian Cancer

EXPERIMENTAL

Participants with ovarian carcinoma received intravenous infusion of Avelumab at a dose of 10.0 mg/kg once every 2 weeks in secondary expansion cohort until confirmed progression, unacceptable toxicity, or any reason for withdrawal from the trial or IMP occurs.

Drug: Avelumab

Secondary Expansion Cohort: Renal Cell Carcinoma (First Line)

EXPERIMENTAL

Participants with Renal cell carcinoma received intravenous infusion of Avelumab at a dose of 10.0 mg/kg once every 2 weeks as a first-line therapy in secondary expansion cohort until confirmed progression, unacceptable toxicity, or any reason for withdrawal from the trial or IMP occurs.

Drug: Avelumab

Secondary Expansion Cohort: Renal Cell Carcinoma (Second Line)

EXPERIMENTAL

Participants with Renal cell carcinoma who failed 1 prior systemic first-line regimen received intravenous infusion of Avelumab at a dose of 10.0 mg/kg once every 2 weeks as a second line treatment in secondary expansion cohort until confirmed progression, unacceptable toxicity, or any reason for withdrawal from the trial or IMP occurs.

Drug: Avelumab

Efficacy Expansion Cohort: Ovarian Cancer

EXPERIMENTAL

Participants with ovarian carcinoma received intravenous infusion of Avelumab at a dose of 10.0 mg/kg once every 2 weeks in efficacy expansion cohort until confirmed progression, unacceptable toxicity, or any reason for withdrawal from the trial or IMP occurs.

Drug: Avelumab

Efficacy Expansion Cohort: Urothelial Carcinoma

EXPERIMENTAL

Participants with urothelial carcinoma received intravenous infusion of Avelumab at a dose of 10.0 mg/kg once every 2 weeks in efficacy expansion cohort until confirmed progression, unacceptable toxicity, or any reason for withdrawal from the trial or IMP occurs.

Drug: Avelumab

Efficacy Expansion Cohort: GC/ GEJC, Third Line

EXPERIMENTAL

Participants with gastric (GC) and gastroesophageal junction cancer (GEJC) who have failed both a first-line chemotherapy regimen and subsequent ramucirumab therapy, received intravenous infusion of Avelumab at a dose of 10.0 mg/kg once every 2 weeks as a third-line treatment in efficacy expansion cohort until confirmed progression, unacceptable toxicity, or any reason for withdrawal from the trial or IMP occurs.

Drug: Avelumab

Efficacy Expansion Cohort: HNSCC

EXPERIMENTAL

Participants with head and neck squamous cell carcinoma (HNSCC) received intravenous infusion of Avelumab at a dose of 10.0 mg/kg once every 2 weeks in efficacy expansion cohort until confirmed progression, unacceptable toxicity, or any reason for withdrawal from the trial or IMP occurs.

Drug: Avelumab

Interventions

Avelumab DRUG

Participants received intravenous infusion of Avelumab in dose escalation and expansion cohorts until confirmed progression, unacceptable toxicity, or any reason for withdrawal from the trial or IMP occurs.

Also known as: MSB0010718C, Anti PD-L1

Dose Escalation Cohort: Avelumab 1.0 mg/kg; Dose Escalation Cohort: Avelumab 10.0 mg/kg; Dose Escalation Cohort: Avelumab 10.0 mg/kg Weekly; Dose Escalation Cohort: Avelumab 20.0 mg/kg; Dose Escalation Cohort: Avelumab 3.0 mg/kg; Efficacy Expansion Cohort: GC/ GEJC, Third Line; Efficacy Expansion Cohort: HNSCC; Efficacy Expansion Cohort: Ovarian Cancer; Efficacy Expansion Cohort: Urothelial Carcinoma; Primary Expansion Cohort: GC/GEJC Non Progressed; Primary Expansion Cohort: GC/GEJC Progressed; Primary Expansion Cohort: Metastatic Breast Cancer; Primary Expansion Cohort: NSCLC, First Line; Primary Expansion Cohort: NSCLC, Post-platinum Doublet; Secondary Expansion Cohort: Adrenocortical Carcinoma; Secondary Expansion Cohort: Castrate-resistant Prostate Cancer; Secondary Expansion Cohort: Colorectal Cancer; Secondary Expansion Cohort: Melanoma; Secondary Expansion Cohort: Mesothelioma; Secondary Expansion Cohort: Ovarian Cancer; Secondary Expansion Cohort: Renal Cell Carcinoma (First Line); Secondary Expansion Cohort: Renal Cell Carcinoma (Second Line); Secondary Expansion Cohort: Urothelial Carcinoma

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• EMD Serono Research & Development Institute, Inc.: lead
• Merck KGaA, Darmstadt, Germany: collaborator

Study Sites (74)

Cancer Treatment Centers of America - Western Regional Medical Center

Goodyear, Arizona, 85338, United States

Location

Scottsdale Healthcare Corporation

Scottsdale, Arizona, 85258-4550, United States

Location

Pinnacle Oncology Hematology

Scottsdale, Arizona, 85258, United States

Location

Highlands Oncology Group

Rogers, Arkansas, 72758, United States

Location

Pacific Cancer Medical Center, Inc.

Anaheim, California, 92801, United States

Location

California Cancer Associates for Research & Excellence, Inc

Encinitas, California, 92024, United States

Location

Healing Hands Oncology and Medical Care

Inglewood, California, 90305, United States

Location

Scripps Health dba Scripps Clinical Research Services

La Jolla, California, 92037, United States

Location

The Angeles Clinic and Research Institute - West LA

Los Angeles, California, 90025, United States

Location

Cedars-Sinai Medical Center - Oncology

Los Angeles, California, 90048, United States

Location

University of California Davis Health System

Sacramento, California, 95817, United States

Location

Sharp Memorial Hospital

San Diego, California, 92123, United States

Location

Georgetown University Medical Center- Research Parent

Washington D.C., District of Columbia, 20057, United States

Location

Holy Cross Hospital

Fort Lauderdale, Florida, 33308, United States

Location

University of Miami

Miami, Florida, 33136, United States

Location

Hematology - Oncology Associates of Treasure Coast - Hematology-Oncology Associates of Treasure Coast

Port Saint Lucie, Florida, 34952, United States

Location

Florida Cancer Specialists

Sarasota, Florida, 34232, United States

Location

Northeast Georgia Cancer Care, LLC

Athens, Georgia, 30607, United States

Location

Peachtree Hematology-Oncology Consultants, PC

Atlanta, Georgia, 30318, United States

Location

Augusta University - formerly Georgia Regents University

Augusta, Georgia, 30912, United States

Location

Northwest Georgia Oncology Centers PC

Marietta, Georgia, 30060, United States

Location

University of Chicago Medical Center

Chicago, Illinois, 60637, United States

Location

Horizon Oncology Research, INC

Lafayette, Indiana, 47905, United States

Location

The Johns Hopkins Hospital

Baltimore, Maryland, 21287-7049, United States

Location

RCCA MD LLC - Bethesda

Bethesda, Maryland, 20817, United States

Location

National Cancer Institute

Bethesda, Maryland, 20892, United States

Location

Maryland Oncology Hematology, P.A.

Rockville, Maryland, 20850, United States

Location

Karmanos Cancer Institute

Detroit, Michigan, 48201, United States

Location

Henry Ford Medical Center

Detroit, Michigan, 48202, United States

Location

Michigan State University

Lansing, Michigan, 48910, United States

Location

Virginia Piper Cancer Institute

Minneapolis, Minnesota, 55407, United States

Location

Kansas City Research Institute, LLC - Phase I Unit

Kansas City, Missouri, 64131, United States

Location

Washington University in St. Louis

St Louis, Missouri, 63110, United States

Location

San Juan Oncology Associates

Farmington, New Mexico, 87401, United States

Location

Columbia University College of Phys & Surgeons

New York, New York, 10032, United States

Location

Montefiore Medical Center PRIME

The Bronx, New York, 10461, United States

Location

University of North Carolina at Chapel Hill

Chapel Hill, North Carolina, 27514, United States

Location

Carolina BioOncology Institute, LLC - Cancer Therapy and Research Center

Huntersville, North Carolina, 28078, United States

Location

UC Health Clinical Trials Office

Cincinnati, Ohio, 45267-0502, United States

Location

University Hospitals Case Medical Center - Case Comprehensive Cancer Center

Cleveland, Ohio, 44106, United States

Location

OSU - James Comprehensive Cancer Center - Division of Hematology

Columbus, Ohio, 43210-1228, United States

Location

Mid Ohio Oncology Hematology, DBA The Mark H. Zangmeister Center - d/b/a The Mark H. Zangmeister Center

Columbus, Ohio, 43219, United States

Location

Oklahoma University Medical Center

Oklahoma City, Oklahoma, 73104, United States

Location

Penn State Univ. Milton S. Hershey Medical Center - MSHMC Cardiology

Hershey, Pennsylvania, 17033, United States

Location

Rhode Island Hospital

Providence, Rhode Island, 02903, United States

Location

Medical University of South Carolina

Charleston, South Carolina, 29245, United States

Location

The West Clinic

Germantown, Tennessee, 38138, United States

Location

Baptist Cancer Center

Memphis, Tennessee, 38120, United States

Location

SCRI - Tennessee Oncology

Nashville, Tennessee, 37203, United States

Location

Texas Oncology, P.A

Dallas, Texas, 75246, United States

Location

Oncology Consultants, P.A.

Houston, Texas, 77030, United States

Location

Texas Oncology, P.A. - Tyler

Tyler, Texas, 75702, United States

Location

Northwest Medical Specialties, PLLC

Lakewood, Washington, 98499-3071, United States

Location

GZA Ziekenhuizen - Campus Sint-Augustinus

Wilrijk, 2610, Belgium

Location

Nemocnice Rudolfa a Stefanie Benesov, a.s.

Benešov, 256 01, Czechia

Location

ICO - Site Paul Papin - service d'oncologie medicale

Angers, 49055, France

Location

Centre Léon Bérard

Lyon, 69008, France

Location

Centre Antoine Lacassagne

Nice, 06189, France

Location

Centre Paul Strauss - Service de Médecine Oncologique

Strasbourg, 67000, France

Location

Universitaetsmedizin der Johannes Gutenberg-Universitaet Mainz - I. Medizinische Klinik Gastroenterologie u Hepato.

Mainz, 55131, Germany

Location

Schwarzwald-Baar Klinikum Villingen-Schwenningen GmbH - Innere Medizin II Haematologie / Onkologie

Villingen-Schwenningen, 78052, Germany

Location

Centrum Onkologii-Instytut im. M. Sklodowskiej Curie - Dept of Digestive System Oncology

Warsaw, 02-781, Poland

Location

Seoul National University Bundang Hospital

Seongnam-si, 13620, South Korea

Location

Korea University Anam Hospital

Seoul, 02841, South Korea

Location

Seoul National University Hospital

Seoul, 03080, South Korea

Location

Severance Hospital, Yonsei University

Seoul, 03722, South Korea

Location

Asan Medical Center

Seoul, 05505, South Korea

Location

Gangnam Severance Hospital, Yonsei University Health System

Seoul, 06273, South Korea

Location

Samsung Medical Center

Seoul, 06351, South Korea

Location

The Catholic University of Korea, Seoul St. Mary's Hospital

Seoul, 06591, South Korea

Location

National Cheng Kung University Hospital

Tainan, 704, Taiwan

Location

National Taiwan University Hospital

Taipei, 100, Taiwan

Location

Sarah Cannon Research Institute UK

London, W1G 6AD, United Kingdom

Location

Derriford Hospital - Dept of Oncology Clinical Trials

Plymouth, PL6 8BQ, United Kingdom

Location

Related Publications (19)

• 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.

  PMID: 28375787 BACKGROUND

• 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.

  PMID: 28373005 BACKGROUND

• 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.

  PMID: 28373007 BACKGROUND

• Redman JM, O'Sullivan Coyne G, Reed CT, Madan RA, Strauss J, Steinberg SJ, Marte J, Cordes L, Heery C, Gulley JL. Avelumab in Patients With Metastatic Colorectal Cancer. Oncologist. 2023 Sep 7;28(9):823-e804. doi: 10.1093/oncolo/oyad162.

  PMID: 37310790 DERIVED

• Madan RA, Redman JM, Karzai F, Dahut WL, Cordes L, Fakhrejahani F, Vu T, Sheikh N, Schlom J, Gulley JL. Avelumab in Men With Metastatic Castration-Resistant Prostate Cancer, Enriched for Patients Treated Previously With a Therapeutic Cancer Vaccine. J Immunother. 2023 May 1;46(4):145-151. doi: 10.1097/CJI.0000000000000459. Epub 2023 Feb 24.

  PMID: 36821354 DERIVED

• 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.

  PMID: 34663640 DERIVED

• 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.

  PMID: 33219092 DERIVED

• 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.

  PMID: 32907924 DERIVED

• 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.

  PMID: 32849281 DERIVED

• 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.

  PMID: 31651359 DERIVED

• 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.

  PMID: 31639039 DERIVED

• 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.

  PMID: 31553054 DERIVED

• 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.

  PMID: 30717797 DERIVED

• 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.

  PMID: 30676622 DERIVED

• 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.

  PMID: 30651126 DERIVED

• 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.

  PMID: 30605211 DERIVED

• 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.

  PMID: 30348224 DERIVED

• 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.

  PMID: 29217288 DERIVED

• 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.

  PMID: 28239472 DERIVED

Related Links

• 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

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung; Breast Neoplasms; Neoplasms; Ovarian Neoplasms; Colorectal Neoplasms; Melanoma; Carcinoma, Transitional Cell; Urinary Bladder Neoplasms; Squamous Cell Carcinoma of Head and Neck; Carcinoma, Renal Cell; Adrenocortical Carcinoma

Interventions

avelumab

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Lung Diseases; Respiratory Tract Diseases; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases; Endocrine Gland Neoplasms; Ovarian Diseases; Adnexal Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Neoplasms, Female; Urogenital Neoplasms; Genital Diseases; Endocrine System Diseases; Gonadal Disorders; Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases; Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms, Nerve Tissue; Nevi and Melanomas; Skin Neoplasms; Carcinoma; Neoplasms, Glandular and Epithelial; Urologic Neoplasms; Urinary Bladder Diseases; Urologic Diseases; Male Urogenital Diseases; Carcinoma, Squamous Cell; Head and Neck Neoplasms; Adenocarcinoma; Kidney Neoplasms; Kidney Diseases; Adrenal Cortex Neoplasms; Adrenal Gland Neoplasms; Adrenal Cortex Diseases; Adrenal Gland Diseases

Results Point of Contact

• Title: Communication Center
• Organization: Merck KGaA, Darmstadt, Germany

service@emdgroup.com

+49-6151-72-5200

Study Officials

• Medical Responsible

  EMD Serono Inc., an affiliate of Merck KGaA, Darmstadt, Germany

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 14, 2013
• First Posted: January 21, 2013
• Study Start: January 31, 2013
• Primary Completion: December 16, 2019
• Study Completion: December 16, 2019
• Last Updated: December 20, 2021
• Results First Posted: December 20, 2021

Record last verified: 2021-10

Locations

PL (1); CZ (1); US (53); DE (2); KR (8); TW (2); GB (2); FR (4); BE (1)