Avelumab in Metastatic or Locally Advanced Solid Tumors (JAVELIN Solid Tumor)
- Registration Number
- NCT01772004
- 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 .
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 1756
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description Primary Expansion Cohort: Metastatic Breast Cancer Avelumab 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. Dose Escalation Cohort: Avelumab 10.0 mg/kg Avelumab 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. Secondary Expansion Cohort: Adrenocortical Carcinoma Avelumab 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. Dose Escalation Cohort: Avelumab 1.0 mg/kg Avelumab 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. Dose Escalation Cohort: Avelumab 3.0 mg/kg Avelumab 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. Dose Escalation Cohort: Avelumab 20.0 mg/kg Avelumab 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. Dose Escalation Cohort: Avelumab 10.0 mg/kg Weekly Avelumab 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. Primary Expansion Cohort: NSCLC, Post-platinum Doublet Avelumab 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. Primary Expansion Cohort: NSCLC, First Line Avelumab 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. Primary Expansion Cohort: GC/GEJC Progressed Avelumab 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. Primary Expansion Cohort: GC/GEJC Non Progressed Avelumab 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. Secondary Expansion Cohort: Colorectal Cancer Avelumab 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. Secondary Expansion Cohort: Castrate-resistant Prostate Cancer Avelumab 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. Secondary Expansion Cohort: Melanoma Avelumab 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. Secondary Expansion Cohort: Mesothelioma Avelumab 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. Secondary Expansion Cohort: Urothelial Carcinoma Avelumab 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. Secondary Expansion Cohort: Ovarian Cancer Avelumab 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. Secondary Expansion Cohort: Renal Cell Carcinoma (First Line) Avelumab 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. Secondary Expansion Cohort: Renal Cell Carcinoma (Second Line) Avelumab 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. Efficacy Expansion Cohort: Ovarian Cancer Avelumab 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. Efficacy Expansion Cohort: GC/ GEJC, Third Line Avelumab 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. Efficacy Expansion Cohort: HNSCC Avelumab 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. Efficacy Expansion Cohort: Urothelial Carcinoma Avelumab 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.
- Primary Outcome Measures
Name Time Method Dose Escalation Cohort (Excluding Once Weekly Avelumab 10 mg/kg Cohort): Number of Participants Experiencing Dose Limiting Toxicities (DLTs) 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.
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) 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.
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) 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.
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) 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.
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) 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.
- Secondary Outcome Measures
Name Time Method 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 The AUC(0-inf) was estimated by determining the total area under the curve of the concentration versus time curve extrapolated to infinity.
Dose Expansion Phase: Minimum Serum Post-dose (Ctrough) Concentration of Avelumab At Day 15, 29, 43, 57, 71, 85, 99, 127 and 169 Serum Ctrough concentration of Avelumab is reported.
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) 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.
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 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.
Dose Expansion Cohort: Progression-Free Survival (PFS) Time According to Response Evaluation Criteria in Solid Tumors Version (RECIST) 1.1 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.
Dose Expansion Cohort: Number of Participants With Positive Programmed Death Receptor-1 Ligand-1 (PD-L1) Biomarker Expression in Tumor Tissue 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'.
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 Cmax is the maximum observed serum concentration obtained directly from the concentration versus time curve.
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) 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.
Dose Escalation and Expansion Cohorts: Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and TEAEs as Per Severity 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.
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 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.
Dose Escalation Cohort (Excluding Once Weekly Avelumab 10 mg/kg Cohort): Time to Reach Maximum Observed Serum Concentration (Tmax) 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 Tmax is time to reach maximum observed serum concentration obtained directly from the concentration versus time curve.
Dose Expansion Phase: Serum Concentration at End of Infusion (CEOI) of Avelumab At Day 1, 15, 29, 43, 85, 127 and 169 Serum concentration at end of infusion (CEOI) of Avelumab is reported.
Dose Expansion Cohort: Overall Survival (OS) Time 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.
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 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.
Dose Escalation Cohort (Excluding Once Weekly Avelumab 10 mg/kg Cohort): Apparent Terminal Half-Life (t1/2) 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 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.
Dose Expansion Cohort: Number of Participants With Immune Related Best Overall Response (irBOR) According to Modified Immune-Related Response Criteria (irRC) 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.
Dose Escalation Cohort: Number of Participants With Best Overall Response (BOR) According to Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 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.
Dose Escalation Cohort (Excluding Once Weekly Avelumab 10 mg/kg Cohort): Programmed Death Ligand 1 (PD-L1) Receptor Occupancy 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.
Dose Expansion Cohort: Duration of Response According to Modified Immune-Related Response Criteria (irRC) Per Investigator Assessment 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.
Dose Expansion Cohort: Number of Participants With Best Overall Response (BOR) According to Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 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.
Dose Expansion Cohort: Immune Related Progression-Free Survival (irPFS) Time According to Modified Immune-Related Response Criteria (irRC) 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.
Primary Expansion Cohorts: Number of Participants With Unconfirmed Response at Week 13 According to Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 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.
Dose Expansion Cohort: Duration of Response According to Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 Per Investigator Assessment 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.
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) 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.
Dose Escalation Cohort (Excluding Once Weekly Avelumab 10 mg/kg Cohort): Number of Participants With at Least 1 Positive Anti Drug Antibodies (ADA) 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.
Dose Expansion Cohort: Number of Participants With Atleast 1 Positive Anti Drug Antibodies (ADA) Assay 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.
Trial Locations
- Locations (74)
Cancer Treatment Centers of America - Western Regional Medical Center
🇺🇸Goodyear, Arizona, United States
Highlands Oncology Group
🇺🇸Rogers, Arkansas, United States
California Cancer Associates for Research & Excellence, Inc
🇺🇸Encinitas, California, United States
Scripps Health dba Scripps Clinical Research Services
🇺🇸La Jolla, California, United States
Cedars-Sinai Medical Center - Oncology
🇺🇸Los Angeles, California, United States
The Angeles Clinic and Research Institute - West LA
🇺🇸Los Angeles, California, United States
University of Chicago Medical Center
🇺🇸Chicago, Illinois, United States
Horizon Oncology Research, INC
🇺🇸Lafayette, Indiana, United States
The Johns Hopkins Hospital
🇺🇸Baltimore, Maryland, United States
Michigan State University
🇺🇸Lansing, Michigan, United States
Columbia University College of Phys & Surgeons
🇺🇸New York, New York, United States
Baptist Cancer Center
🇺🇸Memphis, Tennessee, United States
GZA Ziekenhuizen - Campus Sint-Augustinus
🇧🇪Wilrijk, Belgium
Nemocnice Rudolfa a Stefanie Benesov, a.s.
🇨🇿Benesov, Czechia
ICO - Site Paul Papin - service d'oncologie medicale
🇫🇷Angers cedex 2, France
Centre Antoine Lacassagne
🇫🇷Nice cedex 02, France
Schwarzwald-Baar Klinikum Villingen-Schwenningen GmbH - Innere Medizin II Haematologie / Onkologie
🇩🇪Villingen-Schwenningen, Germany
Seoul National University Hospital
🇰🇷Seoul, Korea, Republic of
University Hospitals Case Medical Center - Case Comprehensive Cancer Center
🇺🇸Cleveland, Ohio, United States
University of Miami
🇺🇸Miami, Florida, United States
Montefiore Medical Center PRIME
🇺🇸Bronx, New York, United States
Virginia Piper Cancer Institute
🇺🇸Minneapolis, Minnesota, United States
SCRI - Tennessee Oncology
🇺🇸Nashville, Tennessee, United States
Peachtree Hematology-Oncology Consultants, PC
🇺🇸Atlanta, Georgia, United States
Sharp Memorial Hospital
🇺🇸San Diego, California, United States
Healing Hands Oncology and Medical Care
🇺🇸Inglewood, California, United States
Northeast Georgia Cancer Care, LLC
🇺🇸Athens, Georgia, United States
Pacific Cancer Medical Center, Inc.
🇺🇸Anaheim, California, United States
Carolina BioOncology Institute, LLC - Cancer Therapy and Research Center
🇺🇸Huntersville, North Carolina, United States
San Juan Oncology Associates
🇺🇸Farmington, New Mexico, United States
Washington University in St. Louis
🇺🇸Saint Louis, Missouri, United States
Augusta University - formerly Georgia Regents University
🇺🇸Augusta, Georgia, United States
Northwest Georgia Oncology Centers PC
🇺🇸Marietta, Georgia, United States
UC Health Clinical Trials Office
🇺🇸Cincinnati, Ohio, United States
Texas Oncology, P.A. - Tyler
🇺🇸Tyler, Texas, United States
OSU - James Comprehensive Cancer Center - Division of Hematology
🇺🇸Columbus, Ohio, United States
Mid Ohio Oncology Hematology, DBA The Mark H. Zangmeister Center - d/b/a The Mark H. Zangmeister Center
🇺🇸Columbus, Ohio, United States
Texas Oncology, P.A
🇺🇸Dallas, Texas, United States
Northwest Medical Specialties, PLLC
🇺🇸Lakewood, Washington, United States
Scottsdale Healthcare Corporation
🇺🇸Scottsdale, Arizona, United States
Holy Cross Hospital
🇺🇸Fort Lauderdale, Florida, United States
Pinnacle Oncology Hematology
🇺🇸Scottsdale, Arizona, United States
Hematology - Oncology Associates of Treasure Coast - Hematology-Oncology Associates of Treasure Coast
🇺🇸Port Saint Lucie, Florida, United States
Severance Hospital, Yonsei University
🇰🇷Seoul, Korea, Republic of
The West Clinic
🇺🇸Germantown, Tennessee, United States
Asan Medical Center
🇰🇷Seoul, Korea, Republic of
Seoul National University Bundang Hospital
🇰🇷Seongnam-si, Korea, Republic of
Georgetown University Medical Center- Research Parent
🇺🇸Washington, District of Columbia, United States
Korea University Anam Hospital
🇰🇷Seoul, Korea, Republic of
Samsung Medical Center
🇰🇷Seoul, Korea, Republic of
National Taiwan University Hospital
🇨🇳Taipei, Taiwan
Universitaetsmedizin der Johannes Gutenberg-Universitaet Mainz - I. Medizinische Klinik Gastroenterologie u Hepato.
🇩🇪Mainz, Germany
Rhode Island Hospital
🇺🇸Providence, Rhode Island, United States
Gangnam Severance Hospital, Yonsei University Health System
🇰🇷Seoul, Korea, Republic of
Florida Cancer Specialists
🇺🇸Sarasota, Florida, United States
Karmanos Cancer Institute
🇺🇸Detroit, Michigan, United States
Henry Ford Medical Center
🇺🇸Detroit, Michigan, United States
Oklahoma University Medical Center
🇺🇸Oklahoma City, Oklahoma, United States
Maryland Oncology Hematology, P.A.
🇺🇸Rockville, Maryland, United States
Penn State Univ. Milton S. Hershey Medical Center - MSHMC Cardiology
🇺🇸Hershey, Pennsylvania, United States
Oncology Consultants, P.A.
🇺🇸Houston, Texas, United States
Centre Paul Strauss - Service de Médecine Oncologique
🇫🇷Strasbourg Cedex, France
The Catholic University of Korea, Seoul St. Mary's Hospital
🇰🇷Seoul, Korea, Republic of
Centrum Onkologii-Instytut im. M. Sklodowskiej Curie - Dept of Digestive System Oncology
🇵🇱Warszawa, Poland
Sarah Cannon Research Institute UK
🇬🇧London, United Kingdom
National Cheng Kung University Hospital
🇨🇳Tainan, Taiwan
Derriford Hospital - Dept of Oncology Clinical Trials
🇬🇧Plymouth, United Kingdom
Centre Léon Bérard
🇫🇷Lyon, France
University of California Davis Health System
🇺🇸Sacramento, California, United States
RCCA MD LLC - Bethesda
🇺🇸Bethesda, Maryland, United States
National Cancer Institute
🇺🇸Bethesda, Maryland, United States
Kansas City Research Institute, LLC - Phase I Unit
🇺🇸Kansas City, Missouri, United States
University of North Carolina at Chapel Hill
🇺🇸Chapel Hill, North Carolina, United States
Medical University of South Carolina
🇺🇸Charleston, South Carolina, United States