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

• ClinicalTrials.gov Identifier: NCT01772004
• Recruitment Status: Completed
• First Posted: January 21, 2013
• Results First Posted: December 20, 2021
• Last Update Posted: December 20, 2021
• Sponsor: EMD Serono Research & Development Institute, Inc.
• Collaborator: Merck KGaA, Darmstadt, Germany
• Information provided by (Responsible Party): EMD Serono ( EMD Serono Research & Development Institute, Inc. )

Study Description

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 .

Condition or disease	Intervention/treatment	Phase
Solid Tumors	Drug: Avelumab	Phase 1

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 1756 participants
• Allocation: Non-Randomized
• Intervention Model: Sequential Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• 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
• Actual Study Start Date: January 31, 2013
• Actual Primary Completion Date: December 16, 2019
• Actual Study Completion Date: December 16, 2019

Arms and Interventions

Arm	Intervention/treatment
Experimental: Dose Escalation Cohort: Avelumab 1.0 mg/kg; 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; 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.; Other Names: MSB0010718C; Anti PD-L1
Experimental: Dose Escalation Cohort: Avelumab 3.0 mg/kg; 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; 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.; Other Names: MSB0010718C; Anti PD-L1
Experimental: Dose Escalation Cohort: Avelumab 10.0 mg/kg; 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; 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.; Other Names: MSB0010718C; Anti PD-L1
Experimental: Dose Escalation Cohort: Avelumab 20.0 mg/kg; 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; 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.; Other Names: MSB0010718C; Anti PD-L1
Experimental: Dose Escalation Cohort: Avelumab 10.0 mg/kg Weekly; 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; 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.; Other Names: MSB0010718C; Anti PD-L1
Experimental: Primary Expansion Cohort: NSCLC, Post-platinum Doublet; 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; 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.; Other Names: MSB0010718C; Anti PD-L1
Experimental: Primary Expansion Cohort: NSCLC, First Line; 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; 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.; Other Names: MSB0010718C; Anti PD-L1
Experimental: Primary Expansion Cohort: Metastatic Breast Cancer; 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; 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.; Other Names: MSB0010718C; Anti PD-L1
Experimental: Primary Expansion Cohort: GC/GEJC Progressed; 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; 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.; Other Names: MSB0010718C; Anti PD-L1
Experimental: Primary Expansion Cohort: GC/GEJC Non Progressed; 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; 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.; Other Names: MSB0010718C; Anti PD-L1
Experimental: Secondary Expansion Cohort: Colorectal Cancer; 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; 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.; Other Names: MSB0010718C; Anti PD-L1
Experimental: Secondary Expansion Cohort: Castrate-resistant Prostate Cancer; 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; 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.; Other Names: MSB0010718C; Anti PD-L1
Experimental: Secondary Expansion Cohort: Adrenocortical Carcinoma; 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; 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.; Other Names: MSB0010718C; Anti PD-L1
Experimental: Secondary Expansion Cohort: Melanoma; 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; 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.; Other Names: MSB0010718C; Anti PD-L1
Experimental: Secondary Expansion Cohort: Mesothelioma; 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; 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.; Other Names: MSB0010718C; Anti PD-L1
Experimental: Secondary Expansion Cohort: Urothelial Carcinoma; 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; 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.; Other Names: MSB0010718C; Anti PD-L1
Experimental: Secondary Expansion Cohort: Ovarian Cancer; 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; 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.; Other Names: MSB0010718C; Anti PD-L1
Experimental: Secondary Expansion Cohort: Renal Cell Carcinoma (First Line); 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; 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.; Other Names: MSB0010718C; Anti PD-L1
Experimental: Secondary Expansion Cohort: Renal Cell Carcinoma (Second Line); 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; 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.; Other Names: MSB0010718C; Anti PD-L1
Experimental: Efficacy Expansion Cohort: Ovarian Cancer; 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; 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.; Other Names: MSB0010718C; Anti PD-L1
Experimental: Efficacy Expansion Cohort: Urothelial Carcinoma; 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; 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.; Other Names: MSB0010718C; Anti PD-L1
Experimental: Efficacy Expansion Cohort: GC/ GEJC, Third Line; 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; 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.; Other Names: MSB0010718C; Anti PD-L1
Experimental: Efficacy Expansion Cohort: HNSCC; 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; 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.; Other Names: MSB0010718C; Anti PD-L1

Outcome Measures

Primary Outcome Measures :

1. Dose Escalation Cohort (Excluding Once Weekly Avelumab 10 mg/kg Cohort): Number of Participants Experiencing Dose Limiting Toxicities (DLTs) [ Time Frame: Dose Escalation: Baseline up to Week 3 ]
   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.
2. 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) [ Time Frame: Ovarian Cancer Efficacy Expansion: Baseline up to Day 620 ]
   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.
3. 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) [ Time Frame: Urothelial Carcinoma Efficacy Expansion: Baseline up to Day 931 ]
   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.
4. 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) [ Time Frame: GC/GEJC, Third Line Efficacy Expansion: Baseline up to Day 871 ]
   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.
5. 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) [ Time Frame: HNSCC Efficacy Expansion: Baseline up to Day 1072 ]
   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.

Secondary Outcome Measures :

1. Dose Escalation and Expansion Cohorts: Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and TEAEs as Per Severity [ Time Frame: Up to Day 2511 ]
   Adverse event(AE): any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with use of study drug, whether or not related to study drug. A serious adverse event(SAE) was an AE that resulted in any of following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect or was otherwise considered medically important. Treatment-emergent events were events between first dose of study drug that were absent before treatment or that worsened relative to pre-treatment state up to 30 days after last administration.TEAEs included both Serious TEAEs and non-serious TEAEs. Severity of TEAEs were graded using National Cancer Institute-Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 4.0 toxicity grades, as follows: Grade 1= Mild, Grade 2= Moderate, Grade 3= Severe, Grade 4= Life-threatening and Grade 5= Death.
2. Dose Escalation and Expansion Cohorts: Number of Participants With Treatment-Related Treatment-Emergent Adverse Events (TEAEs) and Treatment-Related TEAEs as Per Severity [ Time Frame: Baseline up to Day 2511 ]
   AE was defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of study drug, whether or not related to study drug. Treatment-emergent events were the events between first dose of study drug that were absent before treatment or that worsened relative to pre-treatment state up to 30 days after last administration. TEAEs included both Serious TEAEs and non-serious TEAEs. Treatment related AE was defined as having a "Possible" or "Related" relationship to study treatment, as assessed by the Investigator. Severity of Treatment-Related TEAEs were graded using NCI-CTCAE version 4.0 toxicity grades, as follows: Grade 1= Mild, Grade 2= Moderate, Grade 3= Severe, Grade 4= Life-threatening and Grade 5= Death.
3. 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 [ Time Frame: 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 ]
   Area under the serum concentration versus time curve from time zero to the last sampling time t at which the concentration is at or above the lower limit of quantification (LLLQ). AUC(0-t) was calculated according to the mixed log-linear trapezoidal rule.
4. 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 [ Time Frame: 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 ]
   The AUC(0-inf) was estimated by determining the total area under the curve of the concentration versus time curve extrapolated to infinity.
5. Dose Escalation Cohort (Excluding Once Weekly Avelumab 10 mg/kg Cohort): Maximum Observed Serum Concentration (Cmax) of Avelumab [ Time Frame: 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 ]
   Cmax is the maximum observed serum concentration obtained directly from the concentration versus time curve.
6. Dose Escalation Cohort (Excluding Once Weekly Avelumab 10 mg/kg Cohort): Time to Reach Maximum Observed Serum Concentration (Tmax) of Avelumab [ Time Frame: 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 ]
   Tmax is time to reach maximum observed serum concentration obtained directly from the concentration versus time curve.
7. Dose Escalation Cohort (Excluding Once Weekly Avelumab 10 mg/kg Cohort): Apparent Terminal Half-Life (t1/2) of Avelumab [ Time Frame: 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 ]
   Apparent terminal half-life was defined as the time required for the serum concentration of drug to decrease 50 percent in the final stage of its elimination.
8. Dose Expansion Phase: Serum Concentration at End of Infusion (CEOI) of Avelumab [ Time Frame: At Day 1, 15, 29, 43, 85, 127 and 169 ]
   Serum concentration at end of infusion (CEOI) of Avelumab is reported.
9. Dose Expansion Phase: Minimum Serum Post-dose (Ctrough) Concentration of Avelumab [ Time Frame: At Day 15, 29, 43, 57, 71, 85, 99, 127 and 169 ]
   Serum Ctrough concentration of Avelumab is reported.
10. 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) [ Time Frame: Dose Escalation: Baseline up to Day 1023 ]
    irBOR defined as best response of any of immune related complete response (irCR), immune related partial response (irPR), immune related stable disease (irSD) and immune related progressive disease (irPD) recorded from baseline until immune related disease progression and determined according to modified irRC per investigator assessment. irCR: Complete disappearance of all tumor lesions (both index and non-index lesions with no new measurable/unmeasurable lesions). irPR: At least 30% reduction from baseline in the sum of the longest diameter (SLD) of all lesions). irSD: SLD of target and new measurable lesions neither irCR, irPR, or irPD. irPD: SLD of target and new measurable lesions increases greater than or equal to [>=] 20%, confirmed by a repeat, consecutive observations at least 4 weeks from the date first documented. Number of participants with immune-related best overall response in each category (irCR, irPR, irSD, irPD) was reported.
11. Dose Expansion Cohort: Number of Participants With Immune Related Best Overall Response (irBOR) According to Modified Immune-Related Response Criteria (irRC) [ Time Frame: Dose Expansion: Baseline up to Day 2023 ]
    irBOR defined as best response of any of immune related complete response (irCR), immune related partial response (irPR), immune related stable disease (irSD) and immune related progressive disease (irPD) recorded from baseline until immune related disease progression and determined according to modified irRC per investigator assessment. irCR: Complete disappearance of all tumor lesions (both index and non-index lesions with no new measurable/unmeasurable lesions). irPR: At least 30% reduction from baseline in the sum of the longest diameter (SLD) of all lesions). irSD: SLD of target and new measurable lesions neither irCR, irPR, or irPD. irPD: SLD of target and new measurable lesions increases greater than or equal to [>=] 20%, confirmed by a repeat, consecutive observations at least 4 weeks from the date first documented. Number of participants with immune-related best overall response in each category (irCR, irPR, irSD, irPD) was reported.
12. Dose Escalation Cohort: Number of Participants With Best Overall Response (BOR) According to Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 [ Time Frame: Dose Escalation: Baseline up to Day 2511 ]
    BOR was determined according to RECIST v1.1 and as per investigator assessment. BOR is defined as the 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 or recurrence (taking the smallest measurement recorded since start of treatment as reference). CR: Disappearance of all evidence of target and non-target lesions. PR: At least 30 percent (%) reduction from baseline in the sum of the longest diameter (SLD) of all lesions. SD =Neither sufficient increase to qualify for PD nor sufficient shrinkage to qualify for PR. PD is defined as at least a 20 % increase in the SLD, taking as reference the smallest SLD recorded from baseline or appearance of 1 or more new lesions and unequivocal progression of non-target lesions. Number of participants with best overall response in each category (CR, PR, SD, PD) was reported.
13. Dose Expansion Cohort: Number of Participants With Best Overall Response (BOR) According to Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 [ Time Frame: Dose Expansion: Baseline up to Day 2023 ]
    BOR was determined according to RECIST v1.1 and as per investigator assessment. BOR is defined as the 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 or recurrence (taking the smallest measurement recorded since start of treatment as reference). CR: Disappearance of all evidence of target and non-target lesions. PR: At least 30 percent (%) reduction from baseline in the sum of the longest diameter (SLD) of all lesions. SD = Neither sufficient increase to qualify for PD nor sufficient shrinkage to qualify for PR. PD is defined as at least a 20 % increase in the SLD, taking as reference the smallest SLD recorded from baseline or appearance of 1 or more new lesions and unequivocal progression of non-target lesions. Number of participants with best overall response in each category (CR, PR, SD, PD) was reported.
14. 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 [ Time Frame: Secondary Urothelial Carcinoma Dose Expansion: Baseline up to Day 931 ]
    Confirmed Best Overall Response (BOR) was determined according to Response Evaluation Criteria in Solid Tumors (RECIST) v1.1and as adjudicated by an Independent Endpoint Review Committee (IERC) is 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. Number of participants with BOR in each category (CR, PR, SD, PD) were reported.
15. Dose Expansion Cohort: Progression-Free Survival (PFS) Time According to Response Evaluation Criteria in Solid Tumors Version (RECIST) 1.1 [ Time Frame: Dose Expansion: Baseline up to Day 2023 ]
    The PFS time (based on investigator assessments), according to the RECIST 1.1, was defined as the time from first administration of study treatment until first documentation of progressive disease (PD) or death when death occurred within 12 weeks of the last tumor assessment or first administration of study treatment (whichever was later). PD was defined as at least a 20% increase in the sum of longest diameter (SLD), taking as reference the smallest SLD recorded from baseline or the appearance of 1 or more new lesions and unequivocal progression of non-target lesions. The analysis of PFS was performed with a Kaplan-Meier method.
16. Dose Expansion Cohort: Immune Related Progression-Free Survival (irPFS) Time According to Modified Immune-Related Response Criteria (irRC) [ Time Frame: Dose Expansion: Baseline up to Day 2023 ]
    The irPFS time was defined as the time from first administration of study treatment until first documentation of immune-related progressive disease (irPD) or death when death occurred within 12 weeks of the last tumor assessment or first administration of study treatment (whichever was later). irPD: sum of the longest diameters of target and new measurable lesions increases greater than or equal to [>=] 20%, confirmed by a repeat, consecutive observations at least 4 weeks from the date first documented. The analysis of irPFS will be performed with a Kaplan-Meier method. Data for immune related progression-free survival time has been reported.
17. Dose Expansion Cohort: Overall Survival (OS) Time [ Time Frame: Dose Expansion: Baseline up to Day 2023 ]
    Overall survival time was measured as time in months first administration of trial treatment to death. The analysis of OS time was performed with a Kaplan-Meier method.
18. Dose Escalation Cohort (Excluding Once Weekly Avelumab 10 mg/kg Cohort): Programmed Death Ligand 1 (PD-L1) Receptor Occupancy [ Time Frame: Pre-infusion on Day 1; 48 hours after infusion on Day 3; Pre-infusion on Days 15, 43, and 85 ]
    Percentage of PD-L1 receptors occupied by avelumab on human lymphocytes (CD3+ T-cells) was assessed by flow cytometry on peripheral blood mononuclear cell (PBMC) samples. Greater than or equal to [>=] 85 percent [%] of cell viability was required for reliable receptor occupancy assessment.
19. Dose Expansion Cohort: Number of Participants With Positive Programmed Death Receptor-1 Ligand-1 (PD-L1) Biomarker Expression in Tumor Tissue [ Time Frame: Dose Expansion: Baseline up to Day 2023 ]
    PD-L1 assessment was performed using immunohistochemistry. PD-L1 expression status was classified as positive or negative based on the following cut-offs: For tumor cells: Participants were considered PD-L1 expression positive (negative): - if at least (less than) 5% of the tumor cells show PD-L1 membrane staining >= 1+, respectively. This was used as the primary cut-off; - if at least (less than) 25% of the tumor cells show PD-L1 membrane staining >=2+, respectively. This was considered as secondary cut-off; - if at least (less than) 1% of the tumor cells show PD-L1 membrane staining >=1+, respectively. This was used as the tertiary cut-off; - if at least (less than) 50% of the tumor cells show PD-L1 membrane staining >=1+, respectively. This was used as the '50% cut-off'; - if at least (less than) 80% of the tumor cells show PD-L1 membrane staining ≥1+, respectively. This was used as the '80% cut-off'.
20. Primary Expansion Cohorts: Number of Participants With Unconfirmed Response at Week 13 According to Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 [ Time Frame: Week 13 ]
    The response criteria evaluation was carried out according to Response Evaluation Criteria in Solid Tumors (RECIST) 1.1. CR and PR did not need to be confirmed by a subsequent tumor assessment due to blinded central assessment. CR: Disappearance of all target lesions since baseline; PR: At least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum of diameters; SD: Neither sufficient increase to qualify for PD nor sufficient shrinkage to qualify for PR and 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. Number of participants with unconfirmed response at week 13 according to response evaluation criteria in solid tumors (RECIST) version 1.1 were reported.
21. Dose Expansion Cohort: Duration of Response According to Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 Per Investigator Assessment [ Time Frame: Dose Expansion: Baseline up to Day 2023 ]
    Duration of response according to RECIST 1.1, per investigator assessment was calculated for each participant with a confirmed response (complete response [CR] or partial response [PR]) as the time from the first observation of response to the first observation of documented disease progression (or death within 12 weeks of the last tumor assessment). CR: Disappearance of all evidence of target and non-target lesions. PR: At least 30 percent (%) reduction from baseline in the sum of the longest diameter (SLD) of all lesions. Results were calculated based on Kaplan-Meier estimates.
22. Dose Expansion Cohort: Duration of Response According to Modified Immune-Related Response Criteria (irRC) Per Investigator Assessment [ Time Frame: Dose Expansion: Baseline up to Day 2023 ]
    Duration of response according to modified irRC, per investigator assessment was calculated for each participant with a confirmed response (immune-related complete response [irCR] or immune-related partial response [irPR]) as the time from the first observation of response to the first observation of documented disease progression (or death within 12 weeks of the last tumor assessment). irCR: Complete disappearance of all tumor lesions (both index and non-index lesions with no new measurable/unmeasurable lesions). irPR: At least 30% reduction from baseline in the sum of the longest diameter (SLD) of all lesions). Results were calculated based on Kaplan-Meier estimates.
23. 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) [ Time Frame: Efficacy Expansion: Baseline up to Day 1072 ]
    Duration of response according to modified irRC, per investigator assessment was calculated for each participant with a confirmed response (immune-related complete response [irCR] or immune-related partial response [irPR]) as the time from the first observation of response to the first observation of documented disease progression (or death within 12 weeks of the last tumor assessment). irCR: Complete disappearance of all tumor lesions (both index and non-index lesions with no new measurable/unmeasurable lesions). irPR: At least 30% reduction from baseline in the sum of the longest diameter (SLD) of all lesions). Results were calculated based on Kaplan-Meier estimates.
24. 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) [ Time Frame: Efficacy Expansion: Baseline up to Day 1072 ]
    The PFS time (based on IERC), according to the RECIST 1.1, was defined as the time from first administration of study treatment until first documentation of progressive disease (PD) or death when death occurred within 12 weeks of the last tumor assessment or first administration of study treatment (whichever was later). PD was defined as at least a 20% increase in the sum of longest diameter (SLD), taking as reference the smallest SLD recorded from baseline or the appearance of 1 or more new lesions and unequivocal progression of non-target lesions. The analysis of PFS was performed with a Kaplan-Meier method.
25. Dose Escalation Cohort (Excluding Once Weekly Avelumab 10 mg/kg Cohort): Number of Participants With at Least 1 Positive Anti Drug Antibodies (ADA) [ Time Frame: Dose Escalation: Baseline up to Day 1023 ]
    Serum samples were analyzed by a validated electrochemiluminescence immunoassay to detect the presence of antidrug antibodies (ADA). Number of participants with ADA positive results for Avelumab were reported.
26. Dose Expansion Cohort: Number of Participants With Atleast 1 Positive Anti Drug Antibodies (ADA) Assay [ Time Frame: Dose Expansion: Baseline up to Day 2023 ]
    Serum samples were analyzed by a validated electrochemiluminescence immunoassay to detect the presence of antidrug antibodies (ADA). Number of participants with ADA positive results for Avelumab were reported.

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

United States, Arizona

Cancer Treatment Centers of America - Western Regional Medical Center

Goodyear, Arizona, United States, 85338

Scottsdale Healthcare Corporation

Scottsdale, Arizona, United States, 85258-4550

Pinnacle Oncology Hematology

Scottsdale, Arizona, United States, 85258

United States, Arkansas

Highlands Oncology Group

Rogers, Arkansas, United States, 72758

United States, California

Pacific Cancer Medical Center, Inc.

Anaheim, California, United States, 92801

California Cancer Associates for Research & Excellence, Inc

Encinitas, California, United States, 92024

Healing Hands Oncology and Medical Care

Inglewood, California, United States, 90305

Scripps Health dba Scripps Clinical Research Services

La Jolla, California, United States, 92037

The Angeles Clinic and Research Institute - West LA

Los Angeles, California, United States, 90025

Cedars-Sinai Medical Center - Oncology

Los Angeles, California, United States, 90048

University of California Davis Health System

Sacramento, California, United States, 95817

Sharp Memorial Hospital

San Diego, California, United States, 92123

United States, District of Columbia

Georgetown University Medical Center- Research Parent

Washington, District of Columbia, United States, 20057

United States, Florida

Holy Cross Hospital

Fort Lauderdale, Florida, United States, 33308

University of Miami

Miami, Florida, United States, 33136

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

Port Saint Lucie, Florida, United States, 34952

Florida Cancer Specialists

Sarasota, Florida, United States, 34232

United States, Georgia

Northeast Georgia Cancer Care, LLC

Athens, Georgia, United States, 30607

Peachtree Hematology-Oncology Consultants, PC

Atlanta, Georgia, United States, 30318

Augusta University - formerly Georgia Regents University

Augusta, Georgia, United States, 30912

Northwest Georgia Oncology Centers PC

Marietta, Georgia, United States, 30060

United States, Illinois

University of Chicago Medical Center

Chicago, Illinois, United States, 60637

United States, Indiana

Horizon Oncology Research, INC

Lafayette, Indiana, United States, 47905

United States, Maryland

The Johns Hopkins Hospital

Baltimore, Maryland, United States, 21287-7049

RCCA MD LLC - Bethesda

Bethesda, Maryland, United States, 20817

National Cancer Institute

Bethesda, Maryland, United States, 20892

Maryland Oncology Hematology, P.A.

Rockville, Maryland, United States, 20850

United States, Michigan

Karmanos Cancer Institute

Detroit, Michigan, United States, 48201

Henry Ford Medical Center

Detroit, Michigan, United States, 48202

Michigan State University

Lansing, Michigan, United States, 48910

United States, Minnesota

Virginia Piper Cancer Institute

Minneapolis, Minnesota, United States, 55407

United States, Missouri

Kansas City Research Institute, LLC - Phase I Unit

Kansas City, Missouri, United States, 64131

Washington University in St. Louis

Saint Louis, Missouri, United States, 63110

United States, New Mexico

San Juan Oncology Associates

Farmington, New Mexico, United States, 87401

United States, New York

Montefiore Medical Center PRIME

Bronx, New York, United States, 10461

Columbia University College of Phys & Surgeons

New York, New York, United States, 10032

United States, North Carolina

University of North Carolina at Chapel Hill

Chapel Hill, North Carolina, United States, 27514

Carolina BioOncology Institute, LLC - Cancer Therapy and Research Center

Huntersville, North Carolina, United States, 28078

United States, Ohio

UC Health Clinical Trials Office

Cincinnati, Ohio, United States, 45267-0502

University Hospitals Case Medical Center - Case Comprehensive Cancer Center

Cleveland, Ohio, United States, 44106

OSU - James Comprehensive Cancer Center - Division of Hematology

Columbus, Ohio, United States, 43210-1228

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

Columbus, Ohio, United States, 43219

United States, Oklahoma

Oklahoma University Medical Center

Oklahoma City, Oklahoma, United States, 73104

United States, Pennsylvania

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

Hershey, Pennsylvania, United States, 17033

United States, Rhode Island

Rhode Island Hospital

Providence, Rhode Island, United States, 02903

United States, South Carolina

Medical University of South Carolina

Charleston, South Carolina, United States, 29245

United States, Tennessee

The West Clinic

Germantown, Tennessee, United States, 38138

Baptist Cancer Center

Memphis, Tennessee, United States, 38120

SCRI - Tennessee Oncology

Nashville, Tennessee, United States, 37203

United States, Texas

Texas Oncology, P.A

Dallas, Texas, United States, 75246

Oncology Consultants, P.A.

Houston, Texas, United States, 77030

Texas Oncology, P.A. - Tyler

Tyler, Texas, United States, 75702

United States, Washington

Northwest Medical Specialties, PLLC

Lakewood, Washington, United States, 98499-3071

Belgium

GZA Ziekenhuizen - Campus Sint-Augustinus

Wilrijk, Belgium, 2610

Czechia

Nemocnice Rudolfa a Stefanie Benesov, a.s.

Benesov, Czechia, 256 01

France

ICO - Site Paul Papin - service d'oncologie medicale

Angers cedex 2, France, 49055

Centre Léon Bérard

Lyon, France, 69008

Centre Antoine Lacassagne

Nice cedex 02, France, 06189

Centre Paul Strauss - Service de Médecine Oncologique

Strasbourg Cedex, France, 67000

Germany

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

Mainz, Germany, 55131

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

Villingen-Schwenningen, Germany, 78052

Korea, Republic of

Seoul National University Bundang Hospital

Seongnam-si, Korea, Republic of, 13620

Korea University Anam Hospital

Seoul, Korea, Republic of, 02841

Seoul National University Hospital

Seoul, Korea, Republic of, 03080

Severance Hospital, Yonsei University

Seoul, Korea, Republic of, 03722

Asan Medical Center

Seoul, Korea, Republic of, 05505

Gangnam Severance Hospital, Yonsei University Health System

Seoul, Korea, Republic of, 06273

Samsung Medical Center

Seoul, Korea, Republic of, 06351

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

Seoul, Korea, Republic of, 06591

Poland

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

Warszawa, Poland, 02-781

Taiwan

National Cheng Kung University Hospital

Tainan, Taiwan, 704

National Taiwan University Hospital

Taipei, Taiwan, 100

United Kingdom

Sarah Cannon Research Institute UK

London, United Kingdom, W1G 6AD

Derriford Hospital - Dept of Oncology Clinical Trials

Plymouth, United Kingdom, PL6 8BQ

Sponsors and Collaborators

EMD Serono Research & Development Institute, Inc.

Merck KGaA, Darmstadt, Germany

Investigators

• Study Director: Medical Responsible; EMD Serono Inc., an affiliate of Merck KGaA, Darmstadt, Germany

  Study Documents (Full-Text)

Documents provided by EMD Serono ( EMD Serono Research & Development Institute, Inc. ):

Study Protocol  [PDF] August 6, 2018

Statistical Analysis Plan  [PDF] October 12, 2015

More Information

Additional Information:

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 

Publications:

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.

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.

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.

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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. Erratum In: Lancet Oncol. 2018 Jul;19(7):e335.

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.

• Responsible Party: EMD Serono Research & Development Institute, Inc.
• ClinicalTrials.gov Identifier: NCT01772004
• Other Study ID Numbers: EMR 100070-001; 2013-002834-19 ( EudraCT Number )
• First Posted: January 21, 2013
• Results First Posted: December 20, 2021
• Last Update Posted: December 20, 2021
• Last Verified: October 2021

Keywords provided by EMD Serono ( EMD Serono Research & Development Institute, Inc. ):

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)

Additional relevant MeSH terms:

Neoplasms; Avelumab; Antineoplastic Agents, Immunological; Antineoplastic Agents