Solid Tumors
Conditions
Keywords
Solid Tumors, MSB0010718C, anti PD-L1, avelumab, Phase 1
Brief summary
This was a Phase 1, open-label, dose-escalation trial of avelumab (antibody targeting programmed death ligand 1 \[anti PD-L1\]) in Japanese participants with metastatic or locally advanced solid tumors, followed by a consecutive expansion part in Asian participants with gastric cancer.
Interventions
DRUGAvelumab 3 mg/kg
Participants received intravenous infusion of Avelumab over 1 hour duration at a dose of 3 milligrams per kilogram (mg/kg) once every 2 weeks in the dose- escalation cohort until disease progression, unacceptable toxicity or withdrawal from the study or study drug occurred.
Participants received intravenous infusion of Avelumab over 1 hour duration at a dose of 10 mg/kg once every 2 weeks in the dose- escalation cohort and expansion cohort until disease progression, unacceptable toxicity or withdrawal from the study or study drug occurred.
DRUGAvelumab 20 mg/kg
Participants received intravenous infusion of Avelumab over 1 hour duration at a dose of 20 mg/kg once every 2 weeks in the dose- escalation cohort until disease progression, unacceptable toxicity or withdrawal from the study or study drug occurred.
Sponsors
Merck KGaA, Darmstadt, Germany
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
20 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Signed written informed consent * Male or female participants aged greater than or equal to (\>=) 20 years * For dose escalation part: Histologically or cytologically proven metastatic or locally advanced solid tumors, for which no standard therapy exists or standard therapy has failed * For expansion part: * Availability of fresh and archive tumor in formalin fixed paraffin embedded tissue * With histologically or cytologically confirmed recurrent or refractory unresectable Stage IV gastric or gastro-esophageal junctional adenocarcinoma (according to American Joint Committee on Cancer/Union Internationale Contre le Cancer \[UICC\] 7th edition) and whose disease progressed after one or two prior chemotherapy regimen(s) involving both fluoropyrimidines and platinum * Presence of at least 1 measurable lesion according to RECIST version 1.1 * Participants should not have severe peritoneal metastases. The following criteria were applied: * No clinical ileus or subileus * No moderate-to-severe ascites (participants with ascites restricted to the perihepatic space or pelvic cavity) * Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1 at the trial entry and an estimated life expectancy of at least 3 months * Adequate hematological, hepatic and renal function as defined in the protocol * All participants must agree to use effective means of contraception with their partner from entry into the trial through 6 months after the last dose of avelumab
Exclusion criteria
* Concurrent treatment with a non-permitted drug * Prior therapy with any antibody/drug targeting T cell co-regulatory proteins (immune checkpoints) * Concurrent anticancer treatment or concurrent systemic therapy with steroids or other immunosuppressive agents, or use of any investigational drug within 30 days before the start of trial treatment. Short-term administration of steroids (that is, for allergic reactions or the management of immune-related adverse events \[irAE\]) is allowed * Previous malignant disease within the last 5 years with the exception of adequately treated non-melanoma skin cancer, in situ cancer, or other cancer * Non-oncology vaccine therapies for prevention of infection disease (e.g. 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. * 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 * Other protocol defined
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Dose-escalation Cohorts: Number of Participants With Dose Limiting Toxicities (DLTs) | Baseline up to 3 weeks | DLT: any Grade greater than or equal to (\>=) 3 or Adverse Events (AE) according to National Cancer Institute Common Toxicity Criteria for AE Version 4.03 (NCI-CTCAE v4.03); observed during first 3 weeks of dose-escalation part and as being related to Avelumab by Investigator/Sponsor. Following events were not considered as DLT: Grade 3 infusion-related reaction resolving to (\<=) Grade 1 within 6 hours and controlled with medical management; Transient (\<=6 hours) Grade 3 flulike symptoms/fever controlled with medical management and resolved to \<= Grade 1;Transient (\<=24 hours) Grade 3 fatigue, local reactions, headache, nausea, emesis that resolved to \<=Grade1 with/without medical management, Grade 3 diarrhea, Grade 3 skin toxicity, Grade3 out-of-range laboratory values without any clinical correlate that resolves to \<= Grade 1 or Baseline in \< 7 days after medical management; Tumor flare phenomenon defined as local pain, irritation, rash localized at sites of known or suspected tumor. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Expansion Cohort: Area Under the Serum Concentration-Time Curve From the Time of Dosing to the End of Dose Interval (AUC0-336hour [hr]) of Avelumab | Within 6 hours before and the end of the 1-hour infusion (Day 1) and 336 hours after end of infusion | AUC0-336hour was defined as area under the serum concentration-time curve from the time of dosing to the end of dose interval (336 hr). It was calculated by linear trapezoidal summation. |
| Expansion Cohort: Serum Trough Concentration Levels (Ctrough) of Avelumab | Within 6 hours before the 1-hour infusion on Day 15, Day 29, Day 43, Day 85, Day 127 and Day 169. | Ctrough was defined as the trough or minimum serum concentration. |
| Expansion Cohort: Number of Participants With Programmed Death Ligand 1 (PD-L1) Tumor Expression | Time from first dose of study treatment up to 1906 days | The PD-L1 expression was evaluated using an established antiPD-L1 immunohistochemistry (IHC) assay. |
| Expansion Cohort: Absolute Values of Cytokine Levels | Day 1 (Pre-infusion), Day 8 (168 hour after infusion) and Day 43 (Pre-infusion) | Cytokine analysis was performed to evaluate levels of Monocyte chemoattractant protein-1 (MCP-1) and various interleukins (including IL-5, IL-6, IL-8), Tumor necrosis factors-alpha (TNF-alpha) and Interferon-gamma (IFN-gamma) in serum samples. |
| Expansion Cohort: Log Fold Change From Baseline in Cytokine Levels | Baseline (Day 1 [Pre-infusion]), Day 8 (168 hour after infusion) and Day 43 (Pre-infusion) | Cytokine analysis was performed to evaluate levels of Monocyte chemoattractant protein-1 (MCP-1) and various interleukins (including IL-5, IL-6, IL-8), Tumor necrosis factors-alpha (TNF-alpha) and Interferon-gamma (IFN-gamma) in serum samples. Log fold change from baseline (logFC) was defined as logFC (cytokine at time t) = log (cytokine signal at time t) - log (cytokine signal at baseline). |
| Dose-escalation Cohorts: Area Under the Serum Concentration-Time Curve From the Time of Dosing to the Time of the Last Observation (AUC0-t) of Avelumab | Within 6 hours before the infusion, at end of 1-hour infusion (Day 1), 0.5, 1, 2, 4, 6,12, 24, 36, 48, 168 hours after end of infusion | Area under the serum concentration vs time curve from time zero to the last sampling time t at which the concentration was at or above the lower limit of quantification (LLOQ). AUC0-t was calculated by linear trapezoidal summation. |
| Dose-escalation Cohorts: Area Under the Serum Concentration-Time Curve From Time Zero Extrapolated to Infinity (AUC0-inf) of Avelumab | Within 6 hours before the infusion, at end of 1-hour infusion (Day 1), 0.5, 1, 2, 4, 6,12, 24, 36, 48, 168 hours after end of infusion | Area under the curve from the time of dosing extrapolated to infinity was calculated by the linear trapezoidal summation and extrapolated to infinity using Clast/Lambda z after the first intravenous infusion. Clast was the last quantifiable concentration and Lambda z was terminal elimination rate constant determined by log-linear regression analysis of the measured serum concentrations of the terminal log-linear phase. |
| Dose-escalation Cohorts: Maximum Observed Serum Concentration (Cmax) of Avelumab | Within 6 hours before the infusion, at end of 1-hour infusion (Day 1), 0.5, 1, 2, 4, 6,12, 24, 36, 48, 168 hours after end of infusion | Cmax was obtained directly from the concentration versus time curve. |
| Dose-escalation Cohorts: Time to Reach Maximum Observed Serum Concentration (Tmax) of Avelumab | Within 6 hours before the infusion, at end of 1-hour infusion (Day 1), 0.5, 1, 2, 4, 6,12, 24, 36, 48, 168 hours after end of infusion | Tmax was time to reach maximum observed serum concentration obtained directly from the concentration versus time curve. |
| Dose-escalation Cohorts: Terminal Half-Life (t1/2) of Avelumab | Within 6 hours before the infusion, at end of 1-hour infusion (Day 1), 0.5, 1, 2, 4, 6,12, 24, 36, 48, 168 hours after end of infusion | t1/2 was the time measured for the concentration to decrease by one half, determined as 0.693/Lambda z, here Lambda z was the terminal elimination rate constant determined by log-linear regression analysis of the measured serum concentrations of the terminal log-linear phase. |
| Dose-escalation Cohorts: Terminal Elimination Rate Constant (Lambda z) of Avelumab | Within 6 hours before the infusion, at end of 1-hour infusion (Day 1), 0.5, 1, 2, 4, 6,12, 24, 36, 48, 168 hours after end of infusion | Terminal elimination rate constant was determined by log-linear regression analysis of the measured serum concentrations of the terminal log-linear phase. Participant wise data was reported for this outcome measure. |
| Dose-escalation Cohorts: Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs, TEAEs Leading to Death, and TEAEs Leading to Discontinuation | Time from first dose of study treatment up to 2205 days | An Adverse Event (AE) was defined as any unfavourable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of study drug, whether or not considered related to the study drug or worsening of pre-existing medical condition, whether or not related to study drug. A serious adverse event (SAE) was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect or was otherwise considered medically important. TEAEs were those events with onset dates occurring during the on-treatment period for the first time, or if the worsening of an event was during the on-treatment period. TEAEs included both serious TEAEs and non-serious TEAEs. |
| Dose-escalation Cohorts: Absolute Value of Cytokine Levels | Day 1 (Pre-infusion), Day 3 (48 hours after infusion), Day 8 (168 hours after infusion), Day 15 (Pre-infusion), Day 43 (Pre-infusion), Day 45 (48 hours after infusion), Day 50 (168 hours after infusion) | Cytokine analysis was performed to evaluate levels of Rantes, Monocyte chemoattractant protein-1 (MCP-1) and various interleukins (including IL-1 beta, IL-2, IL-4, IL-6, IL-10, IL-12p70, IL-13, IL-8), Tumor necrosis factors-alpha (TNF-alpha) and Interferon-gamma (IFN-gamma) in serum samples. |
| Dose-escalation Cohorts: Log Fold Change From Baseline in Cytokine Levels | Baseline (Day 1 [Pre-infusion]), Day 3 (48 hours after infusion), Day 8 (168 hours after infusion), Day 15 (Pre-infusion), Day 43 (Pre-infusion), Day 45 (48 hours after infusion), Day 50 (168 hours after infusion) | Cytokine analysis was performed to evaluate levels of Rantes, Monocyte chemoattractant protein-1 (MCP-1) and various interleukins (including IL-1beta, IL-2, IL-4, IL-6, IL-10, IL-12p70, IL-13, IL-8), Tumor necrosis factors-alpha (TNF-alpha) and Interferon-gamma (IFN-gamma) in serum samples. Log fold change from baseline (logFC) was defined as logFC (cytokine at time t) = log (cytokine signal at time t) - log (cytokine signal at baseline). |
| Dose-escalation Cohorts: Number of Participants With Treatment-Emergent Positive Human Anti-Human Antibody (HAHA) | Day 15 up to Day 2205 | Participants not having positive HAHA prior to treatment with Avelumab and with at least one positive post-baseline result in the HAHA assay were termed as treatment-emergent. Treatment-emergent participants were further classified as Transient Positive or Persistent positive. Participants were considered as transient positive if time between first and last positive result was less than 16 weeks apart and a negative result at the most recent visit. Participants were considered as persistent positive if time between first and last positive result greater than or equal to \[\>=\] 16 weeks apart or a positive evaluation at the most recent visit. Number of participants with treatment-emergent positive HAHA were reported. |
| Expansion Cohort: Number of Participants With Best Overall Response (BOR) According to Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 | Time from first dose of study treatment up to 1906 days | Confirmed BOR was defined as the best response of any of the complete response (CR), partial response (PR), stable disease (SD) and progressive disease (PD) recorded from the date of randomization until disease progression or recurrence (taking the smallest measurement recorded since the start of treatment as reference). CR: Disappearance of all evidence of target and non-target lesions. PR: At least 30% 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 was defined as at least a 20% increase in the 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. Number of participants with best overall response in each category (CR, PR, SD, PD) was reported. |
| Expansion Cohort: Number of Participants With Immune-related Best Overall Response (irBOR) According to Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 | Time from first dose of study treatment up to 1906 days | BOR: 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 the date of randomization until disease progression or recurrence (taking the smallest measurement recorded since the start of treatment as reference). 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. |
| Expansion Cohort: Progression-Free Survival (PFS) Time According to Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 | Time from first dose of study treatment up to 1906 days | PFS was defined as the time from date of randomization until date of the first documentation of progressive disease (PD) or death due to any cause in the absence of documented PD, whichever occurs first. PD was defined as at least a 20 percent (%) 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. PFS was measured using Kaplan-Meier (KM) estimates. |
| Expansion Cohort: Immune-related Progression-Free Survival (irPFS) Time According to Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 | Time from first dose of study treatment up to 1906 days | irPFS was defined as the time from the first dose of study treatment to the date of first documentation of immune-related progressive disease \[irPD\] (which was subsequently confirmed) or death due to any cause, whichever occurred first. irPD was defined as the sum of the longest diameters of target and new measurable lesions increases greater than or equal to \[\>=\] 20 percent (%), confirmed by a repeat, consecutive observations at least 4 weeks from the date first documented. |
| Expansion Cohort: Overall Survival (OS) Time | Time from first dose of study treatment up to 1906 days | The OS time was defined as the time from randomization to the date of death. The participants who were still alive at the time of data analysis or who were lost to follow-up OS time was censored at the last recorded date that the participant was known to be alive before the data cutoff date. OS was measured using Kaplan-Meier (KM) estimates. |
| Expansion Cohort: Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs, TEAEs Leading to Death, and TEAEs Leading to Discontinuation | Time from first dose of study treatment up to 1906 days | An Adverse Event (AE) was defined as any unfavourable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of study drug, whether or not considered related to the study drug or worsening of pre-existing medical condition, whether or not related to study drug. A serious adverse event (SAE) was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect or was otherwise considered medically important. TEAEs were those events with onset dates occurring during the on-treatment period for the first time, or if the worsening of an event was during the on-treatment period. TEAEs included both serious TEAEs and non-serious TEAEs. |
| Expansion Cohort: Number of Participants With Treatment-Emergent Positive Human Anti-Human Antibody (HAHA) | Day 15 up to Day 1906 | Number of participants with positive HAHA were reported. Participants not having positive HAHA prior to treatment with avelumab and with at least one positive post-baseline result in the HAHA assay were characterized as treatment-emergent. Treatment-emergent participants were further classified as Transient Positive or Persistent positive participants were considered as transient positive if time between first and last positive result was less than 16 weeks apart and a negative result at the most recent visit. Participants were considered as persistent positive if time between first and last positive result \>=16 weeks apart or a positive evaluation at the most recent visit. |
| Dose-escalation Cohorts: Programmed Death Ligand 1 (PD-L1) Receptor Occupancy | Pre-infusion on Day 1; 4 and 48 hours after infusion on Day 3; Pre-infusion on Days 15, 29, 43, and 85 | Percentage of PD-L1 receptors occupied by avelumab on human lymphocytes (CD3+ 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. |
Countries
Germany
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Dose-escalation Cohort: Avelumab 3 mg/kg Participants received intravenous infusion of Avelumab over 1 hour duration at a dose of 3 milligrams per kilogram (mg/kg) once every 2 weeks in the dose-escalation cohort until disease progression, unacceptable toxicity or withdrawal from the study or study drug occurred. | 5 |
| Dose-escalation Cohort: Avelumab 10 mg/kg Participants received intravenous infusion of Avelumab over 1 hour duration at a dose of 10 mg/kg once every 2 weeks in the dose-escalation cohort until disease progression, unacceptable toxicity or withdrawal from the study or study drug occurred. | 6 |
| Dose-escalation Cohort: Avelumab 20 mg/kg Participants received intravenous infusion of Avelumab over 1 hour duration at a dose of 20 mg/kg once every 2 weeks in the dose-escalation cohort until disease progression, unacceptable toxicity or withdrawal from the study or study drug occurred. | 6 |
| Expansion Cohort: Avelumab 10 mg/kg Participants received intravenous infusion of Avelumab over 1 hour duration at a dose of 10 mg/kg once every 2 weeks in the expansion cohort until disease progression, unacceptable toxicity or withdrawal from the study or study drug occurred. | 40 |
| Total | 57 |
Baseline characteristics
| Characteristic | Dose-escalation Cohort: Avelumab 3 mg/kg | Dose-escalation Cohort: Avelumab 10 mg/kg | Dose-escalation Cohort: Avelumab 20 mg/kg | Expansion Cohort: Avelumab 10 mg/kg | Total |
|---|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 2 Participants | 1 Participants | 4 Participants | 18 Participants | 25 Participants |
| Age, Categorical Between 18 and 65 years | 3 Participants | 5 Participants | 2 Participants | 22 Participants | 32 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 5 Participants | 6 Participants | 6 Participants | 40 Participants | 57 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 5 Participants | 6 Participants | 6 Participants | 40 Participants | 57 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Female | 2 Participants | 2 Participants | 3 Participants | 11 Participants | 18 Participants |
| Sex: Female, Male Male | 3 Participants | 4 Participants | 3 Participants | 29 Participants | 39 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 4 / 5 | 3 / 6 | 4 / 6 | 36 / 40 |
| other Total, other adverse events | 5 / 5 | 6 / 6 | 5 / 6 | 38 / 40 |
| serious Total, serious adverse events | 1 / 5 | 0 / 6 | 2 / 6 | 11 / 40 |
Outcome results
Primary
Dose-escalation Cohorts: Number of Participants With Dose Limiting Toxicities (DLTs)
DLT: any Grade greater than or equal to (\>=) 3 or Adverse Events (AE) according to National Cancer Institute Common Toxicity Criteria for AE Version 4.03 (NCI-CTCAE v4.03); observed during first 3 weeks of dose-escalation part and as being related to Avelumab by Investigator/Sponsor. Following events were not considered as DLT: Grade 3 infusion-related reaction resolving to (\<=) Grade 1 within 6 hours and controlled with medical management; Transient (\<=6 hours) Grade 3 flulike symptoms/fever controlled with medical management and resolved to \<= Grade 1;Transient (\<=24 hours) Grade 3 fatigue, local reactions, headache, nausea, emesis that resolved to \<=Grade1 with/without medical management, Grade 3 diarrhea, Grade 3 skin toxicity, Grade3 out-of-range laboratory values without any clinical correlate that resolves to \<= Grade 1 or Baseline in \< 7 days after medical management; Tumor flare phenomenon defined as local pain, irritation, rash localized at sites of known or suspected tumor.
Time frame: Baseline up to 3 weeks
Population: DLT analysis set included all participants with data used for implementing the dose-escalation schedule.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Dose-escalation Cohort: Avelumab 3 mg/kg | Dose-escalation Cohorts: Number of Participants With Dose Limiting Toxicities (DLTs) | 0 Participants |
| Dose-escalation Cohort: Avelumab 10 mg/kg | Dose-escalation Cohorts: Number of Participants With Dose Limiting Toxicities (DLTs) | 0 Participants |
| Dose-escalation Cohort: Avelumab 20 mg/kg | Dose-escalation Cohorts: Number of Participants With Dose Limiting Toxicities (DLTs) | 0 Participants |
Secondary
Dose-escalation Cohorts: Absolute Value of Cytokine Levels
Cytokine analysis was performed to evaluate levels of Rantes, Monocyte chemoattractant protein-1 (MCP-1) and various interleukins (including IL-1 beta, IL-2, IL-4, IL-6, IL-10, IL-12p70, IL-13, IL-8), Tumor necrosis factors-alpha (TNF-alpha) and Interferon-gamma (IFN-gamma) in serum samples.
Time frame: Day 1 (Pre-infusion), Day 3 (48 hours after infusion), Day 8 (168 hours after infusion), Day 15 (Pre-infusion), Day 43 (Pre-infusion), Day 45 (48 hours after infusion), Day 50 (168 hours after infusion)
Population: Safety analysis set included all participants who have received at least 1 dose of study treatment. Here number analyzed signified those participants who were evaluable for this outcome measure at the specified time points for the given category.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Dose-escalation Cohort: Avelumab 3 mg/kg | Dose-escalation Cohorts: Absolute Value of Cytokine Levels | IL-1beta: Day 3: 48 hours After Infusion | 0.255 nanogram per liter (ng/L) | Standard Deviation 0 |
| Dose-escalation Cohort: Avelumab 3 mg/kg | Dose-escalation Cohorts: Absolute Value of Cytokine Levels | IL-6: Day 43: Pre- Infusion | 2.215 nanogram per liter (ng/L) | Standard Deviation 3.279 |
| Dose-escalation Cohort: Avelumab 3 mg/kg | Dose-escalation Cohorts: Absolute Value of Cytokine Levels | IL-12P70: Day 15: Pre- Infusion | 0.200 nanogram per liter (ng/L) | Standard Deviation 0 |
| Dose-escalation Cohort: Avelumab 3 mg/kg | Dose-escalation Cohorts: Absolute Value of Cytokine Levels | IL-1beta: Day 1: Pre-Infusion | 0.255 nanogram per liter (ng/L) | Standard Deviation 0 |
| Dose-escalation Cohort: Avelumab 3 mg/kg | Dose-escalation Cohorts: Absolute Value of Cytokine Levels | IL-6: Day 45: 48 hours After Infusion | 2.888 nanogram per liter (ng/L) | Standard Deviation 4.548 |
| Dose-escalation Cohort: Avelumab 3 mg/kg | Dose-escalation Cohorts: Absolute Value of Cytokine Levels | TNF-alpha: Day 3: 48 hours After Infusion | 3.482 nanogram per liter (ng/L) | Standard Deviation 0.971 |
| Dose-escalation Cohort: Avelumab 3 mg/kg | Dose-escalation Cohorts: Absolute Value of Cytokine Levels | IL-13: Day 50:168 hours After Infusion 4 | 0.680 nanogram per liter (ng/L) | Standard Deviation 0.344 |
| Dose-escalation Cohort: Avelumab 3 mg/kg | Dose-escalation Cohorts: Absolute Value of Cytokine Levels | IL-6: Day 50: 168 hours After Infusion | 1.468 nanogram per liter (ng/L) | Standard Deviation 1.544 |
| Dose-escalation Cohort: Avelumab 3 mg/kg | Dose-escalation Cohorts: Absolute Value of Cytokine Levels | IL-1beta: Day 8: 168 hours After Infusion | 0.255 nanogram per liter (ng/L) | Standard Deviation 0 |
| Dose-escalation Cohort: Avelumab 3 mg/kg | Dose-escalation Cohorts: Absolute Value of Cytokine Levels | IL-13: Day 45: 48 hours After Infusion | 0.650 nanogram per liter (ng/L) | Standard Deviation 0.398 |
| Dose-escalation Cohort: Avelumab 3 mg/kg | Dose-escalation Cohorts: Absolute Value of Cytokine Levels | MCP-1: Day 50: 168 hours After Infusion | 274.320 nanogram per liter (ng/L) | Standard Deviation 49.826 |
| Dose-escalation Cohort: Avelumab 3 mg/kg | Dose-escalation Cohorts: Absolute Value of Cytokine Levels | IL-8: Day 50: 168 hours After Infusion | 65.448 nanogram per liter (ng/L) | Standard Deviation 104.447 |
| Dose-escalation Cohort: Avelumab 3 mg/kg | Dose-escalation Cohorts: Absolute Value of Cytokine Levels | IL-13: Day 43: Pre- Infusion | 0.508 nanogram per liter (ng/L) | Standard Deviation 0.377 |
| Dose-escalation Cohort: Avelumab 3 mg/kg | Dose-escalation Cohorts: Absolute Value of Cytokine Levels | Rantes: Day 1: Pre-Infusion | 32292.35 nanogram per liter (ng/L) | Standard Deviation 24365.33 |
| Dose-escalation Cohort: Avelumab 3 mg/kg | Dose-escalation Cohorts: Absolute Value of Cytokine Levels | IL-13: Day 15: Pre- Infusion | 0.456 nanogram per liter (ng/L) | Standard Deviation 0.301 |
| Dose-escalation Cohort: Avelumab 3 mg/kg | Dose-escalation Cohorts: Absolute Value of Cytokine Levels | Rantes: Day 8: 168 hours After Infusion | 36607.67 nanogram per liter (ng/L) | Standard Deviation 19388.38 |
| Dose-escalation Cohort: Avelumab 3 mg/kg | Dose-escalation Cohorts: Absolute Value of Cytokine Levels | Rantes: Day 45: 48 hours After Infusion | 28777.63 nanogram per liter (ng/L) | Standard Deviation 10267.15 |
| Dose-escalation Cohort: Avelumab 3 mg/kg | Dose-escalation Cohorts: Absolute Value of Cytokine Levels | TNF-alpha: Day 1: Pre-Infusion | 2.304 nanogram per liter (ng/L) | Standard Deviation 0.564 |
| Dose-escalation Cohort: Avelumab 3 mg/kg | Dose-escalation Cohorts: Absolute Value of Cytokine Levels | Rantes: Day 50: 168 hours After Infusion | 38235.52 nanogram per liter (ng/L) | Standard Deviation 6740.02 |
| Dose-escalation Cohort: Avelumab 3 mg/kg | Dose-escalation Cohorts: Absolute Value of Cytokine Levels | IL-13: Day 8: 168 hours After Infusion | 0.684 nanogram per liter (ng/L) | Standard Deviation 0.407 |
| Dose-escalation Cohort: Avelumab 3 mg/kg | Dose-escalation Cohorts: Absolute Value of Cytokine Levels | TNF-alpha: Day 8: 168 hours After Infusion | 2.440 nanogram per liter (ng/L) | Standard Deviation 0.763 |
| Dose-escalation Cohort: Avelumab 3 mg/kg | Dose-escalation Cohorts: Absolute Value of Cytokine Levels | IL-8: Day 15: Pre- Infusion | 24.372 nanogram per liter (ng/L) | Standard Deviation 25.645 |
| Dose-escalation Cohort: Avelumab 3 mg/kg | Dose-escalation Cohorts: Absolute Value of Cytokine Levels | IL-13: Day 3: 48 hours After Infusion | 0.314 nanogram per liter (ng/L) | Standard Deviation 0.165 |
| Dose-escalation Cohort: Avelumab 3 mg/kg | Dose-escalation Cohorts: Absolute Value of Cytokine Levels | TNF-alpha: Day 50: 168 hours After Infusion | 3.180 nanogram per liter (ng/L) | Standard Deviation 2.2 |
| Dose-escalation Cohort: Avelumab 3 mg/kg | Dose-escalation Cohorts: Absolute Value of Cytokine Levels | Rantes: Day 43: Pre-Infusion | 30657.45 nanogram per liter (ng/L) | Standard Deviation 6773.47 |
| Dose-escalation Cohort: Avelumab 3 mg/kg | Dose-escalation Cohorts: Absolute Value of Cytokine Levels | IL-10: Day 50:168 hours After Infusion | 0.906 nanogram per liter (ng/L) | Standard Deviation 1.227 |
| Dose-escalation Cohort: Avelumab 3 mg/kg | Dose-escalation Cohorts: Absolute Value of Cytokine Levels | IL-8: Day 1: Pre-Infusion | 23.210 nanogram per liter (ng/L) | Standard Deviation 26.035 |
| Dose-escalation Cohort: Avelumab 3 mg/kg | Dose-escalation Cohorts: Absolute Value of Cytokine Levels | IL-1beta: Day 43: Pre- Infusion | 0.255 nanogram per liter (ng/L) | Standard Deviation 0 |
| Dose-escalation Cohort: Avelumab 3 mg/kg | Dose-escalation Cohorts: Absolute Value of Cytokine Levels | IL-10: Day 45: 48 hours After Infusion | 1.574 nanogram per liter (ng/L) | Standard Deviation 2.463 |
| Dose-escalation Cohort: Avelumab 3 mg/kg | Dose-escalation Cohorts: Absolute Value of Cytokine Levels | IL-10: Day 43: Pre -Infusion | 0.790 nanogram per liter (ng/L) | Standard Deviation 0.77 |
| Dose-escalation Cohort: Avelumab 3 mg/kg | Dose-escalation Cohorts: Absolute Value of Cytokine Levels | IFN-gamma: Day 1: Pre-Infusion | 9.094 nanogram per liter (ng/L) | Standard Deviation 5.03 |
| Dose-escalation Cohort: Avelumab 3 mg/kg | Dose-escalation Cohorts: Absolute Value of Cytokine Levels | IL-12P70: Day 43: Pre- Infusion | 0.200 nanogram per liter (ng/L) | Standard Deviation 0 |
| Dose-escalation Cohort: Avelumab 3 mg/kg | Dose-escalation Cohorts: Absolute Value of Cytokine Levels | IL-10: Day 15: Pre- Infusion | 0.686 nanogram per liter (ng/L) | Standard Deviation 0.415 |
| Dose-escalation Cohort: Avelumab 3 mg/kg | Dose-escalation Cohorts: Absolute Value of Cytokine Levels | IFN-gamma: Day 3: 48 hours After Infusion | 17.716 nanogram per liter (ng/L) | Standard Deviation 10.063 |
| Dose-escalation Cohort: Avelumab 3 mg/kg | Dose-escalation Cohorts: Absolute Value of Cytokine Levels | IFN-gamma: Day 45: 48 hours After Infusion | 21.153 nanogram per liter (ng/L) | Standard Deviation 19.586 |
| Dose-escalation Cohort: Avelumab 3 mg/kg | Dose-escalation Cohorts: Absolute Value of Cytokine Levels | IFN-gamma: Day 8: 168 hours After Infusion | 15.016 nanogram per liter (ng/L) | Standard Deviation 17.665 |
| Dose-escalation Cohort: Avelumab 3 mg/kg | Dose-escalation Cohorts: Absolute Value of Cytokine Levels | IL-2: Day 8: 168 hours After Infusion | 0.354 nanogram per liter (ng/L) | Standard Deviation 0.162 |
| Dose-escalation Cohort: Avelumab 3 mg/kg | Dose-escalation Cohorts: Absolute Value of Cytokine Levels | IFN-gamma: Day 43: Pre-Infusion | 9.758 nanogram per liter (ng/L) | Standard Deviation 3.838 |
| Dose-escalation Cohort: Avelumab 3 mg/kg | Dose-escalation Cohorts: Absolute Value of Cytokine Levels | IFN-gamma: Day 15: Pre-Infusion | 21.347 nanogram per liter (ng/L) | Standard Deviation 23.831 |
| Dose-escalation Cohort: Avelumab 3 mg/kg | Dose-escalation Cohorts: Absolute Value of Cytokine Levels | IL-10: Day 8: 168 hours After Infusion | 0.675 nanogram per liter (ng/L) | Standard Deviation 0.68 |
| Dose-escalation Cohort: Avelumab 3 mg/kg | Dose-escalation Cohorts: Absolute Value of Cytokine Levels | IL-8: Day 45: 48 hours After Infusion | 51.015 nanogram per liter (ng/L) | Standard Deviation 74.76 |
| Dose-escalation Cohort: Avelumab 3 mg/kg | Dose-escalation Cohorts: Absolute Value of Cytokine Levels | Rantes: Day 15: Pre-Infusion | 59985.74 nanogram per liter (ng/L) | Standard Deviation 21964.23 |
| Dose-escalation Cohort: Avelumab 3 mg/kg | Dose-escalation Cohorts: Absolute Value of Cytokine Levels | IL-2: Day 15: Pre-Infusion | 0.320 nanogram per liter (ng/L) | Standard Deviation 0.13 |
| Dose-escalation Cohort: Avelumab 3 mg/kg | Dose-escalation Cohorts: Absolute Value of Cytokine Levels | IL-8: Day 8: 168 hours After Infusion | 31.082 nanogram per liter (ng/L) | Standard Deviation 35.176 |
| Dose-escalation Cohort: Avelumab 3 mg/kg | Dose-escalation Cohorts: Absolute Value of Cytokine Levels | Rantes: Day 3: 48 hours After Infusion | 31514.77 nanogram per liter (ng/L) | Standard Deviation 13931.92 |
| Dose-escalation Cohort: Avelumab 3 mg/kg | Dose-escalation Cohorts: Absolute Value of Cytokine Levels | IL-2: Day 43: Pre- Infusion | 0.388 nanogram per liter (ng/L) | Standard Deviation 0.148 |
| Dose-escalation Cohort: Avelumab 3 mg/kg | Dose-escalation Cohorts: Absolute Value of Cytokine Levels | IL-12P70: Day 45: 48 hours After Infusion | 0.200 nanogram per liter (ng/L) | Standard Deviation 0 |
| Dose-escalation Cohort: Avelumab 3 mg/kg | Dose-escalation Cohorts: Absolute Value of Cytokine Levels | MCP-1: Day 45: 48 hours After Infusion | 258.265 nanogram per liter (ng/L) | Standard Deviation 57.606 |
| Dose-escalation Cohort: Avelumab 3 mg/kg | Dose-escalation Cohorts: Absolute Value of Cytokine Levels | IL-2: Day 45: 48 hours After Infusion | 0.438 nanogram per liter (ng/L) | Standard Deviation 0.388 |
| Dose-escalation Cohort: Avelumab 3 mg/kg | Dose-escalation Cohorts: Absolute Value of Cytokine Levels | IL-12P70: Day 1: Pre-Infusion | 0.200 nanogram per liter (ng/L) | Standard Deviation 0 |
| Dose-escalation Cohort: Avelumab 3 mg/kg | Dose-escalation Cohorts: Absolute Value of Cytokine Levels | MCP-1: Day 43: Pre- Infusion | 282.053 nanogram per liter (ng/L) | Standard Deviation 65.125 |
| Dose-escalation Cohort: Avelumab 3 mg/kg | Dose-escalation Cohorts: Absolute Value of Cytokine Levels | IL-2: Day 50: 168 hours After Infusion | 0.448 nanogram per liter (ng/L) | Standard Deviation 0.241 |
| Dose-escalation Cohort: Avelumab 3 mg/kg | Dose-escalation Cohorts: Absolute Value of Cytokine Levels | IL-8: Day 3: 48 hours After Infusion | 30.122 nanogram per liter (ng/L) | Standard Deviation 28.378 |
| Dose-escalation Cohort: Avelumab 3 mg/kg | Dose-escalation Cohorts: Absolute Value of Cytokine Levels | MCP-1: Day 15: Pre- Infusion | 257.888 nanogram per liter (ng/L) | Standard Deviation 93.74 |
| Dose-escalation Cohort: Avelumab 3 mg/kg | Dose-escalation Cohorts: Absolute Value of Cytokine Levels | IL-4: Day 1: Pre-Infusion | 0.100 nanogram per liter (ng/L) | Standard Deviation 0 |
| Dose-escalation Cohort: Avelumab 3 mg/kg | Dose-escalation Cohorts: Absolute Value of Cytokine Levels | IL-12P70: Day 50: 168 hours After Infusion | 0.200 nanogram per liter (ng/L) | Standard Deviation 0 |
| Dose-escalation Cohort: Avelumab 3 mg/kg | Dose-escalation Cohorts: Absolute Value of Cytokine Levels | MCP-1: Day 8: 168 hours After Infusion | 257.706 nanogram per liter (ng/L) | Standard Deviation 69.318 |
| Dose-escalation Cohort: Avelumab 3 mg/kg | Dose-escalation Cohorts: Absolute Value of Cytokine Levels | IL-4: Day 3: 48 hours After Infusion | 0.100 nanogram per liter (ng/L) | Standard Deviation 0 |
| Dose-escalation Cohort: Avelumab 3 mg/kg | Dose-escalation Cohorts: Absolute Value of Cytokine Levels | IL-12P70: Day 3: 48 hours After Infusion | 0.200 nanogram per liter (ng/L) | Standard Deviation 0 |
| Dose-escalation Cohort: Avelumab 3 mg/kg | Dose-escalation Cohorts: Absolute Value of Cytokine Levels | MCP-1: Day 3: 48 hours After Infusion | 289.148 nanogram per liter (ng/L) | Standard Deviation 69.117 |
| Dose-escalation Cohort: Avelumab 3 mg/kg | Dose-escalation Cohorts: Absolute Value of Cytokine Levels | IL-4: Day 8: 168 hours After Infusion | 0.100 nanogram per liter (ng/L) | Standard Deviation 0 |
| Dose-escalation Cohort: Avelumab 3 mg/kg | Dose-escalation Cohorts: Absolute Value of Cytokine Levels | TNF-alpha: Day 45: 48 hours After Infusion | 3.983 nanogram per liter (ng/L) | Standard Deviation 3.359 |
| Dose-escalation Cohort: Avelumab 3 mg/kg | Dose-escalation Cohorts: Absolute Value of Cytokine Levels | MCP-1: Day 1: Pre-Infusion | 243.664 nanogram per liter (ng/L) | Standard Deviation 55.976 |
| Dose-escalation Cohort: Avelumab 3 mg/kg | Dose-escalation Cohorts: Absolute Value of Cytokine Levels | IL-4: Day 15: Pre-Infusion | 0.100 nanogram per liter (ng/L) | Standard Deviation 0 |
| Dose-escalation Cohort: Avelumab 3 mg/kg | Dose-escalation Cohorts: Absolute Value of Cytokine Levels | IL-10: Day 1: Pre-Infusion | 0.442 nanogram per liter (ng/L) | Standard Deviation 0.47 |
| Dose-escalation Cohort: Avelumab 3 mg/kg | Dose-escalation Cohorts: Absolute Value of Cytokine Levels | IL-6: Day 3: 48 hours After Infusion | 1.398 nanogram per liter (ng/L) | Standard Deviation 0.713 |
| Dose-escalation Cohort: Avelumab 3 mg/kg | Dose-escalation Cohorts: Absolute Value of Cytokine Levels | IL-4: Day 43: Pre- Infusion | 0.100 nanogram per liter (ng/L) | Standard Deviation 0 |
| Dose-escalation Cohort: Avelumab 3 mg/kg | Dose-escalation Cohorts: Absolute Value of Cytokine Levels | IL-10: Day 3: 48 hours After Infusion | 0.768 nanogram per liter (ng/L) | Standard Deviation 0.495 |
| Dose-escalation Cohort: Avelumab 3 mg/kg | Dose-escalation Cohorts: Absolute Value of Cytokine Levels | IL-2: Day 3: 48 hours After Infusion | 0.396 nanogram per liter (ng/L) | Standard Deviation 0.126 |
| Dose-escalation Cohort: Avelumab 3 mg/kg | Dose-escalation Cohorts: Absolute Value of Cytokine Levels | IL-4: Day 45: 48 hours After Infusion | 0.100 nanogram per liter (ng/L) | Standard Deviation 0 |
| Dose-escalation Cohort: Avelumab 3 mg/kg | Dose-escalation Cohorts: Absolute Value of Cytokine Levels | IFN-gamma: Day 50: 168 hours After Infusion | 11.635 nanogram per liter (ng/L) | Standard Deviation 6.705 |
| Dose-escalation Cohort: Avelumab 3 mg/kg | Dose-escalation Cohorts: Absolute Value of Cytokine Levels | IL-2: Day 1: Pre-Infusion | 0.400 nanogram per liter (ng/L) | Standard Deviation 0.22 |
| Dose-escalation Cohort: Avelumab 3 mg/kg | Dose-escalation Cohorts: Absolute Value of Cytokine Levels | IL-4: Day 50: 168 hours After Infusion | 0.100 nanogram per liter (ng/L) | Standard Deviation 0 |
| Dose-escalation Cohort: Avelumab 3 mg/kg | Dose-escalation Cohorts: Absolute Value of Cytokine Levels | IL-8: Day 43: Pre-Infusion | 56.310 nanogram per liter (ng/L) | Standard Deviation 88.524 |
| Dose-escalation Cohort: Avelumab 3 mg/kg | Dose-escalation Cohorts: Absolute Value of Cytokine Levels | IL-1beta: Day 50: 168 hours After Infusion | 0.255 nanogram per liter (ng/L) | Standard Deviation 0 |
| Dose-escalation Cohort: Avelumab 3 mg/kg | Dose-escalation Cohorts: Absolute Value of Cytokine Levels | IL-6: Day 1: Pre-Infusion | 1.372 nanogram per liter (ng/L) | Standard Deviation 0.917 |
| Dose-escalation Cohort: Avelumab 3 mg/kg | Dose-escalation Cohorts: Absolute Value of Cytokine Levels | TNF-alpha: Day 43: Pre-Infusion | 2.720 nanogram per liter (ng/L) | Standard Deviation 0.908 |
| Dose-escalation Cohort: Avelumab 3 mg/kg | Dose-escalation Cohorts: Absolute Value of Cytokine Levels | IL-13: Day 1: Pre-Infusion | 0.540 nanogram per liter (ng/L) | Standard Deviation 0.426 |
| Dose-escalation Cohort: Avelumab 3 mg/kg | Dose-escalation Cohorts: Absolute Value of Cytokine Levels | IL-1beta: Day 45: 48 hours After Infusion | 0.255 nanogram per liter (ng/L) | Standard Deviation 0 |
| Dose-escalation Cohort: Avelumab 3 mg/kg | Dose-escalation Cohorts: Absolute Value of Cytokine Levels | IL-6: Day 8: 168 hours After Infusion | 1.740 nanogram per liter (ng/L) | Standard Deviation 1.27 |
| Dose-escalation Cohort: Avelumab 3 mg/kg | Dose-escalation Cohorts: Absolute Value of Cytokine Levels | IL-12P70: Day 8: 168 hours After Infusion | 0.200 nanogram per liter (ng/L) | Standard Deviation 0 |
| Dose-escalation Cohort: Avelumab 3 mg/kg | Dose-escalation Cohorts: Absolute Value of Cytokine Levels | IL-1beta: Day 15: Pre- Infusion | 0.255 nanogram per liter (ng/L) | Standard Deviation 0 |
| Dose-escalation Cohort: Avelumab 3 mg/kg | Dose-escalation Cohorts: Absolute Value of Cytokine Levels | IL-6: Day 15: Pre- Infusion | 2.032 nanogram per liter (ng/L) | Standard Deviation 2.62 |
| Dose-escalation Cohort: Avelumab 3 mg/kg | Dose-escalation Cohorts: Absolute Value of Cytokine Levels | TNF-alpha: Day 15: Pre-Infusion | 2.832 nanogram per liter (ng/L) | Standard Deviation 1.523 |
| Dose-escalation Cohort: Avelumab 10 mg/kg | Dose-escalation Cohorts: Absolute Value of Cytokine Levels | Rantes: Day 50: 168 hours After Infusion | 52287.81 nanogram per liter (ng/L) | Standard Deviation 35615.67 |
| Dose-escalation Cohort: Avelumab 10 mg/kg | Dose-escalation Cohorts: Absolute Value of Cytokine Levels | IFN-gamma: Day 50: 168 hours After Infusion | 16.503 nanogram per liter (ng/L) | Standard Deviation 16.671 |
| Dose-escalation Cohort: Avelumab 10 mg/kg | Dose-escalation Cohorts: Absolute Value of Cytokine Levels | IL-12P70: Day 3: 48 hours After Infusion | 0.395 nanogram per liter (ng/L) | Standard Deviation 0.373 |
| Dose-escalation Cohort: Avelumab 10 mg/kg | Dose-escalation Cohorts: Absolute Value of Cytokine Levels | IL-12P70: Day 15: Pre- Infusion | 0.395 nanogram per liter (ng/L) | Standard Deviation 0.478 |
| Dose-escalation Cohort: Avelumab 10 mg/kg | Dose-escalation Cohorts: Absolute Value of Cytokine Levels | IL-12P70: Day 43: Pre- Infusion | 0.465 nanogram per liter (ng/L) | Standard Deviation 0.375 |
| Dose-escalation Cohort: Avelumab 10 mg/kg | Dose-escalation Cohorts: Absolute Value of Cytokine Levels | IL-12P70: Day 45: 48 hours After Infusion | 0.447 nanogram per liter (ng/L) | Standard Deviation 0.419 |
| Dose-escalation Cohort: Avelumab 10 mg/kg | Dose-escalation Cohorts: Absolute Value of Cytokine Levels | IL-12P70: Day 50: 168 hours After Infusion | 0.488 nanogram per liter (ng/L) | Standard Deviation 0.479 |
| Dose-escalation Cohort: Avelumab 10 mg/kg | Dose-escalation Cohorts: Absolute Value of Cytokine Levels | IL-10: Day 3: 48 hours After Infusion | 0.850 nanogram per liter (ng/L) | Standard Deviation 0.506 |
| Dose-escalation Cohort: Avelumab 10 mg/kg | Dose-escalation Cohorts: Absolute Value of Cytokine Levels | IL-10: Day 50:168 hours After Infusion | 2.199 nanogram per liter (ng/L) | Standard Deviation 3.698 |
| Dose-escalation Cohort: Avelumab 10 mg/kg | Dose-escalation Cohorts: Absolute Value of Cytokine Levels | IL-13: Day 1: Pre-Infusion | 0.972 nanogram per liter (ng/L) | Standard Deviation 0.23 |
| Dose-escalation Cohort: Avelumab 10 mg/kg | Dose-escalation Cohorts: Absolute Value of Cytokine Levels | IL-1beta: Day 3: 48 hours After Infusion | 0.255 nanogram per liter (ng/L) | Standard Deviation 0 |
| Dose-escalation Cohort: Avelumab 10 mg/kg | Dose-escalation Cohorts: Absolute Value of Cytokine Levels | IL-1beta: Day 8: 168 hours After Infusion | 0.348 nanogram per liter (ng/L) | Standard Deviation 0.227 |
| Dose-escalation Cohort: Avelumab 10 mg/kg | Dose-escalation Cohorts: Absolute Value of Cytokine Levels | IL-1beta: Day 15: Pre- Infusion | 0.255 nanogram per liter (ng/L) | Standard Deviation 0 |
| Dose-escalation Cohort: Avelumab 10 mg/kg | Dose-escalation Cohorts: Absolute Value of Cytokine Levels | IL-1beta: Day 43: Pre- Infusion | 0.363 nanogram per liter (ng/L) | Standard Deviation 0.263 |
| Dose-escalation Cohort: Avelumab 10 mg/kg | Dose-escalation Cohorts: Absolute Value of Cytokine Levels | IL-2: Day 8: 168 hours After Infusion | 0.475 nanogram per liter (ng/L) | Standard Deviation 0.33 |
| Dose-escalation Cohort: Avelumab 10 mg/kg | Dose-escalation Cohorts: Absolute Value of Cytokine Levels | IL-2: Day 15: Pre-Infusion | 0.300 nanogram per liter (ng/L) | Standard Deviation 0.209 |
| Dose-escalation Cohort: Avelumab 10 mg/kg | Dose-escalation Cohorts: Absolute Value of Cytokine Levels | IL-2: Day 43: Pre- Infusion | 0.500 nanogram per liter (ng/L) | Standard Deviation 0.273 |
| Dose-escalation Cohort: Avelumab 10 mg/kg | Dose-escalation Cohorts: Absolute Value of Cytokine Levels | IL-2: Day 45: 48 hours After Infusion | 0.470 nanogram per liter (ng/L) | Standard Deviation 0.345 |
| Dose-escalation Cohort: Avelumab 10 mg/kg | Dose-escalation Cohorts: Absolute Value of Cytokine Levels | IL-2: Day 50: 168 hours After Infusion | 0.465 nanogram per liter (ng/L) | Standard Deviation 0.278 |
| Dose-escalation Cohort: Avelumab 10 mg/kg | Dose-escalation Cohorts: Absolute Value of Cytokine Levels | IL-4: Day 1: Pre-Infusion | 0.100 nanogram per liter (ng/L) | Standard Deviation 0 |
| Dose-escalation Cohort: Avelumab 10 mg/kg | Dose-escalation Cohorts: Absolute Value of Cytokine Levels | IL-4: Day 3: 48 hours After Infusion | 0.100 nanogram per liter (ng/L) | Standard Deviation 0 |
| Dose-escalation Cohort: Avelumab 10 mg/kg | Dose-escalation Cohorts: Absolute Value of Cytokine Levels | IL-4: Day 8: 168 hours After Infusion | 0.100 nanogram per liter (ng/L) | Standard Deviation 0 |
| Dose-escalation Cohort: Avelumab 10 mg/kg | Dose-escalation Cohorts: Absolute Value of Cytokine Levels | IL-4: Day 15: Pre-Infusion | 0.100 nanogram per liter (ng/L) | Standard Deviation 0 |
| Dose-escalation Cohort: Avelumab 10 mg/kg | Dose-escalation Cohorts: Absolute Value of Cytokine Levels | IL-4: Day 43: Pre- Infusion | 0.100 nanogram per liter (ng/L) | Standard Deviation 0 |
| Dose-escalation Cohort: Avelumab 10 mg/kg | Dose-escalation Cohorts: Absolute Value of Cytokine Levels | IL-4: Day 45: 48 hours After Infusion | 0.100 nanogram per liter (ng/L) | Standard Deviation 0 |
| Dose-escalation Cohort: Avelumab 10 mg/kg | Dose-escalation Cohorts: Absolute Value of Cytokine Levels | IL-4: Day 50: 168 hours After Infusion | 0.100 nanogram per liter (ng/L) | Standard Deviation 0 |
| Dose-escalation Cohort: Avelumab 10 mg/kg | Dose-escalation Cohorts: Absolute Value of Cytokine Levels | IL-6: Day 1: Pre-Infusion | 3.633 nanogram per liter (ng/L) | Standard Deviation 6.078 |
| Dose-escalation Cohort: Avelumab 10 mg/kg | Dose-escalation Cohorts: Absolute Value of Cytokine Levels | IL-6: Day 3: 48 hours After Infusion | 3.843 nanogram per liter (ng/L) | Standard Deviation 5.018 |
| Dose-escalation Cohort: Avelumab 10 mg/kg | Dose-escalation Cohorts: Absolute Value of Cytokine Levels | IL-6: Day 8: 168 hours After Infusion | 2.922 nanogram per liter (ng/L) | Standard Deviation 3.538 |
| Dose-escalation Cohort: Avelumab 10 mg/kg | Dose-escalation Cohorts: Absolute Value of Cytokine Levels | IL-6: Day 15: Pre- Infusion | 3.325 nanogram per liter (ng/L) | Standard Deviation 2.939 |
| Dose-escalation Cohort: Avelumab 10 mg/kg | Dose-escalation Cohorts: Absolute Value of Cytokine Levels | IL-6: Day 43: Pre- Infusion | 1.978 nanogram per liter (ng/L) | Standard Deviation 2.07 |
| Dose-escalation Cohort: Avelumab 10 mg/kg | Dose-escalation Cohorts: Absolute Value of Cytokine Levels | IL-6: Day 45: 48 hours After Infusion | 3.583 nanogram per liter (ng/L) | Standard Deviation 6.013 |
| Dose-escalation Cohort: Avelumab 10 mg/kg | Dose-escalation Cohorts: Absolute Value of Cytokine Levels | IL-6: Day 50: 168 hours After Infusion | 4.082 nanogram per liter (ng/L) | Standard Deviation 6.986 |
| Dose-escalation Cohort: Avelumab 10 mg/kg | Dose-escalation Cohorts: Absolute Value of Cytokine Levels | MCP-1: Day 50: 168 hours After Infusion | 241.980 nanogram per liter (ng/L) | Standard Deviation 70.308 |
| Dose-escalation Cohort: Avelumab 10 mg/kg | Dose-escalation Cohorts: Absolute Value of Cytokine Levels | TNF-alpha: Day 3: 48 hours After Infusion | 4.403 nanogram per liter (ng/L) | Standard Deviation 1.578 |
| Dose-escalation Cohort: Avelumab 10 mg/kg | Dose-escalation Cohorts: Absolute Value of Cytokine Levels | TNF-alpha: Day 8: 168 hours After Infusion | 3.233 nanogram per liter (ng/L) | Standard Deviation 1.174 |
| Dose-escalation Cohort: Avelumab 10 mg/kg | Dose-escalation Cohorts: Absolute Value of Cytokine Levels | TNF-alpha: Day 50: 168 hours After Infusion | 3.967 nanogram per liter (ng/L) | Standard Deviation 2.515 |
| Dose-escalation Cohort: Avelumab 10 mg/kg | Dose-escalation Cohorts: Absolute Value of Cytokine Levels | IL-8: Day 50: 168 hours After Infusion | 28.783 nanogram per liter (ng/L) | Standard Deviation 11.963 |
| Dose-escalation Cohort: Avelumab 10 mg/kg | Dose-escalation Cohorts: Absolute Value of Cytokine Levels | IFN-gamma: Day 1: Pre-Infusion | 5.928 nanogram per liter (ng/L) | Standard Deviation 4.331 |
| Dose-escalation Cohort: Avelumab 10 mg/kg | Dose-escalation Cohorts: Absolute Value of Cytokine Levels | IFN-gamma: Day 8: 168 hours After Infusion | 8.782 nanogram per liter (ng/L) | Standard Deviation 3.118 |
| Dose-escalation Cohort: Avelumab 10 mg/kg | Dose-escalation Cohorts: Absolute Value of Cytokine Levels | IFN-gamma: Day 15: Pre-Infusion | 8.937 nanogram per liter (ng/L) | Standard Deviation 2.557 |
| Dose-escalation Cohort: Avelumab 10 mg/kg | Dose-escalation Cohorts: Absolute Value of Cytokine Levels | IFN-gamma: Day 43: Pre-Infusion | 15.947 nanogram per liter (ng/L) | Standard Deviation 10.844 |
| Dose-escalation Cohort: Avelumab 10 mg/kg | Dose-escalation Cohorts: Absolute Value of Cytokine Levels | IFN-gamma: Day 45: 48 hours After Infusion | 25.295 nanogram per liter (ng/L) | Standard Deviation 28.939 |
| Dose-escalation Cohort: Avelumab 10 mg/kg | Dose-escalation Cohorts: Absolute Value of Cytokine Levels | IL-12P70: Day 1: Pre-Infusion | 0.412 nanogram per liter (ng/L) | Standard Deviation 0.401 |
| Dose-escalation Cohort: Avelumab 10 mg/kg | Dose-escalation Cohorts: Absolute Value of Cytokine Levels | IL-12P70: Day 8: 168 hours After Infusion | 0.368 nanogram per liter (ng/L) | Standard Deviation 0.412 |
| Dose-escalation Cohort: Avelumab 10 mg/kg | Dose-escalation Cohorts: Absolute Value of Cytokine Levels | IL-10: Day 1: Pre-Infusion | 0.504 nanogram per liter (ng/L) | Standard Deviation 0.29 |
| Dose-escalation Cohort: Avelumab 10 mg/kg | Dose-escalation Cohorts: Absolute Value of Cytokine Levels | IL-10: Day 8: 168 hours After Infusion | 0.993 nanogram per liter (ng/L) | Standard Deviation 0.779 |
| Dose-escalation Cohort: Avelumab 10 mg/kg | Dose-escalation Cohorts: Absolute Value of Cytokine Levels | IL-10: Day 15: Pre- Infusion | 1.013 nanogram per liter (ng/L) | Standard Deviation 0.838 |
| Dose-escalation Cohort: Avelumab 10 mg/kg | Dose-escalation Cohorts: Absolute Value of Cytokine Levels | IL-10: Day 43: Pre -Infusion | 2.098 nanogram per liter (ng/L) | Standard Deviation 3.332 |
| Dose-escalation Cohort: Avelumab 10 mg/kg | Dose-escalation Cohorts: Absolute Value of Cytokine Levels | IL-10: Day 45: 48 hours After Infusion | 3.826 nanogram per liter (ng/L) | Standard Deviation 7.268 |
| Dose-escalation Cohort: Avelumab 10 mg/kg | Dose-escalation Cohorts: Absolute Value of Cytokine Levels | IL-13: Day 3: 48 hours After Infusion | 0.995 nanogram per liter (ng/L) | Standard Deviation 0.525 |
| Dose-escalation Cohort: Avelumab 10 mg/kg | Dose-escalation Cohorts: Absolute Value of Cytokine Levels | IL-13: Day 8: 168 hours After Infusion | 1.000 nanogram per liter (ng/L) | Standard Deviation 0.372 |
| Dose-escalation Cohort: Avelumab 10 mg/kg | Dose-escalation Cohorts: Absolute Value of Cytokine Levels | IL-13: Day 15: Pre- Infusion | 1.073 nanogram per liter (ng/L) | Standard Deviation 0.297 |
| Dose-escalation Cohort: Avelumab 10 mg/kg | Dose-escalation Cohorts: Absolute Value of Cytokine Levels | IL-13: Day 43: Pre- Infusion | 1.080 nanogram per liter (ng/L) | Standard Deviation 0.513 |
| Dose-escalation Cohort: Avelumab 10 mg/kg | Dose-escalation Cohorts: Absolute Value of Cytokine Levels | IL-13: Day 45: 48 hours After Infusion | 0.840 nanogram per liter (ng/L) | Standard Deviation 0.312 |
| Dose-escalation Cohort: Avelumab 10 mg/kg | Dose-escalation Cohorts: Absolute Value of Cytokine Levels | IL-13: Day 50:168 hours After Infusion 4 | 0.910 nanogram per liter (ng/L) | Standard Deviation 0.574 |
| Dose-escalation Cohort: Avelumab 10 mg/kg | Dose-escalation Cohorts: Absolute Value of Cytokine Levels | IL-1beta: Day 1: Pre-Infusion | 0.255 nanogram per liter (ng/L) | Standard Deviation 0 |
| Dose-escalation Cohort: Avelumab 10 mg/kg | Dose-escalation Cohorts: Absolute Value of Cytokine Levels | IL-1beta: Day 45: 48 hours After Infusion | 0.543 nanogram per liter (ng/L) | Standard Deviation 0.704 |
| Dose-escalation Cohort: Avelumab 10 mg/kg | Dose-escalation Cohorts: Absolute Value of Cytokine Levels | IL-1beta: Day 50: 168 hours After Infusion | 0.516 nanogram per liter (ng/L) | Standard Deviation 0.639 |
| Dose-escalation Cohort: Avelumab 10 mg/kg | Dose-escalation Cohorts: Absolute Value of Cytokine Levels | IL-2: Day 1: Pre-Infusion | 0.452 nanogram per liter (ng/L) | Standard Deviation 0.274 |
| Dose-escalation Cohort: Avelumab 10 mg/kg | Dose-escalation Cohorts: Absolute Value of Cytokine Levels | IL-2: Day 3: 48 hours After Infusion | 0.670 nanogram per liter (ng/L) | Standard Deviation 0.334 |
| Dose-escalation Cohort: Avelumab 10 mg/kg | Dose-escalation Cohorts: Absolute Value of Cytokine Levels | MCP-1: Day 1: Pre-Infusion | 209.280 nanogram per liter (ng/L) | Standard Deviation 31.895 |
| Dose-escalation Cohort: Avelumab 10 mg/kg | Dose-escalation Cohorts: Absolute Value of Cytokine Levels | MCP-1: Day 3: 48 hours After Infusion | 250.230 nanogram per liter (ng/L) | Standard Deviation 71.66 |
| Dose-escalation Cohort: Avelumab 10 mg/kg | Dose-escalation Cohorts: Absolute Value of Cytokine Levels | MCP-1: Day 8: 168 hours After Infusion | 229.240 nanogram per liter (ng/L) | Standard Deviation 56.104 |
| Dose-escalation Cohort: Avelumab 10 mg/kg | Dose-escalation Cohorts: Absolute Value of Cytokine Levels | MCP-1: Day 15: Pre- Infusion | 226.445 nanogram per liter (ng/L) | Standard Deviation 28.636 |
| Dose-escalation Cohort: Avelumab 10 mg/kg | Dose-escalation Cohorts: Absolute Value of Cytokine Levels | MCP-1: Day 43: Pre- Infusion | 218.855 nanogram per liter (ng/L) | Standard Deviation 45.141 |
| Dose-escalation Cohort: Avelumab 10 mg/kg | Dose-escalation Cohorts: Absolute Value of Cytokine Levels | MCP-1: Day 45: 48 hours After Infusion | 268.657 nanogram per liter (ng/L) | Standard Deviation 84.748 |
| Dose-escalation Cohort: Avelumab 10 mg/kg | Dose-escalation Cohorts: Absolute Value of Cytokine Levels | Rantes: Day 1: Pre-Infusion | 33583.68 nanogram per liter (ng/L) | Standard Deviation 26542.38 |
| Dose-escalation Cohort: Avelumab 10 mg/kg | Dose-escalation Cohorts: Absolute Value of Cytokine Levels | Rantes: Day 3: 48 hours After Infusion | 54874.62 nanogram per liter (ng/L) | Standard Deviation 45162.06 |
| Dose-escalation Cohort: Avelumab 10 mg/kg | Dose-escalation Cohorts: Absolute Value of Cytokine Levels | Rantes: Day 8: 168 hours After Infusion | 52933.35 nanogram per liter (ng/L) | Standard Deviation 37662.84 |
| Dose-escalation Cohort: Avelumab 10 mg/kg | Dose-escalation Cohorts: Absolute Value of Cytokine Levels | Rantes: Day 15: Pre-Infusion | 45301.97 nanogram per liter (ng/L) | Standard Deviation 19703.88 |
| Dose-escalation Cohort: Avelumab 10 mg/kg | Dose-escalation Cohorts: Absolute Value of Cytokine Levels | Rantes: Day 43: Pre-Infusion | 43532.09 nanogram per liter (ng/L) | Standard Deviation 25175.05 |
| Dose-escalation Cohort: Avelumab 10 mg/kg | Dose-escalation Cohorts: Absolute Value of Cytokine Levels | Rantes: Day 45: 48 hours After Infusion | 41629.09 nanogram per liter (ng/L) | Standard Deviation 25017.89 |
| Dose-escalation Cohort: Avelumab 10 mg/kg | Dose-escalation Cohorts: Absolute Value of Cytokine Levels | IFN-gamma: Day 3: 48 hours After Infusion | 10.868 nanogram per liter (ng/L) | Standard Deviation 3.609 |
| Dose-escalation Cohort: Avelumab 10 mg/kg | Dose-escalation Cohorts: Absolute Value of Cytokine Levels | TNF-alpha: Day 1: Pre-Infusion | 2.582 nanogram per liter (ng/L) | Standard Deviation 0.986 |
| Dose-escalation Cohort: Avelumab 10 mg/kg | Dose-escalation Cohorts: Absolute Value of Cytokine Levels | TNF-alpha: Day 15: Pre-Infusion | 3.155 nanogram per liter (ng/L) | Standard Deviation 1.154 |
| Dose-escalation Cohort: Avelumab 10 mg/kg | Dose-escalation Cohorts: Absolute Value of Cytokine Levels | TNF-alpha: Day 43: Pre-Infusion | 3.490 nanogram per liter (ng/L) | Standard Deviation 1.987 |
| Dose-escalation Cohort: Avelumab 10 mg/kg | Dose-escalation Cohorts: Absolute Value of Cytokine Levels | TNF-alpha: Day 45: 48 hours After Infusion | 3.935 nanogram per liter (ng/L) | Standard Deviation 2.316 |
| Dose-escalation Cohort: Avelumab 10 mg/kg | Dose-escalation Cohorts: Absolute Value of Cytokine Levels | IL-8: Day 1: Pre-Infusion | 20.517 nanogram per liter (ng/L) | Standard Deviation 7.254 |
| Dose-escalation Cohort: Avelumab 10 mg/kg | Dose-escalation Cohorts: Absolute Value of Cytokine Levels | IL-8: Day 3: 48 hours After Infusion | 31.717 nanogram per liter (ng/L) | Standard Deviation 14.891 |
| Dose-escalation Cohort: Avelumab 10 mg/kg | Dose-escalation Cohorts: Absolute Value of Cytokine Levels | IL-8: Day 8: 168 hours After Infusion | 29.750 nanogram per liter (ng/L) | Standard Deviation 20.021 |
| Dose-escalation Cohort: Avelumab 10 mg/kg | Dose-escalation Cohorts: Absolute Value of Cytokine Levels | IL-8: Day 15: Pre- Infusion | 23.817 nanogram per liter (ng/L) | Standard Deviation 12.85 |
| Dose-escalation Cohort: Avelumab 10 mg/kg | Dose-escalation Cohorts: Absolute Value of Cytokine Levels | IL-8: Day 43: Pre-Infusion | 25.733 nanogram per liter (ng/L) | Standard Deviation 14.433 |
| Dose-escalation Cohort: Avelumab 10 mg/kg | Dose-escalation Cohorts: Absolute Value of Cytokine Levels | IL-8: Day 45: 48 hours After Infusion | 30.083 nanogram per liter (ng/L) | Standard Deviation 17.206 |
| Dose-escalation Cohort: Avelumab 20 mg/kg | Dose-escalation Cohorts: Absolute Value of Cytokine Levels | IL-1beta: Day 3: 48 hours After Infusion | 0.346 nanogram per liter (ng/L) | Standard Deviation 0.222 |
| Dose-escalation Cohort: Avelumab 20 mg/kg | Dose-escalation Cohorts: Absolute Value of Cytokine Levels | IL-1beta: Day 1: Pre-Infusion | 0.255 nanogram per liter (ng/L) | Standard Deviation 0 |
| Dose-escalation Cohort: Avelumab 20 mg/kg | Dose-escalation Cohorts: Absolute Value of Cytokine Levels | IL-6: Day 15: Pre- Infusion | 1.890 nanogram per liter (ng/L) | Standard Deviation 1.097 |
| Dose-escalation Cohort: Avelumab 20 mg/kg | Dose-escalation Cohorts: Absolute Value of Cytokine Levels | IL-6: Day 8: 168 hours After Infusion | 1.788 nanogram per liter (ng/L) | Standard Deviation 0.529 |
| Dose-escalation Cohort: Avelumab 20 mg/kg | Dose-escalation Cohorts: Absolute Value of Cytokine Levels | IL-1beta: Day 43: Pre- Infusion | 0.255 nanogram per liter (ng/L) | Standard Deviation 0 |
| Dose-escalation Cohort: Avelumab 20 mg/kg | Dose-escalation Cohorts: Absolute Value of Cytokine Levels | IL-6: Day 3: 48 hours After Infusion | 6.433 nanogram per liter (ng/L) | Standard Deviation 11.449 |
| Dose-escalation Cohort: Avelumab 20 mg/kg | Dose-escalation Cohorts: Absolute Value of Cytokine Levels | IL-13: Day 45: 48 hours After Infusion | 0.848 nanogram per liter (ng/L) | Standard Deviation 0.469 |
| Dose-escalation Cohort: Avelumab 20 mg/kg | Dose-escalation Cohorts: Absolute Value of Cytokine Levels | IL-1beta: Day 45: 48 hours After Infusion | 0.255 nanogram per liter (ng/L) | Standard Deviation 0 |
| Dose-escalation Cohort: Avelumab 20 mg/kg | Dose-escalation Cohorts: Absolute Value of Cytokine Levels | IL-4: Day 50: 168 hours After Infusion | 0.100 nanogram per liter (ng/L) | Standard Deviation 0 |
| Dose-escalation Cohort: Avelumab 20 mg/kg | Dose-escalation Cohorts: Absolute Value of Cytokine Levels | IFN-gamma: Day 45: 48 hours After Infusion | 41.253 nanogram per liter (ng/L) | Standard Deviation 63.326 |
| Dose-escalation Cohort: Avelumab 20 mg/kg | Dose-escalation Cohorts: Absolute Value of Cytokine Levels | IL-1beta: Day 50: 168 hours After Infusion | 0.255 nanogram per liter (ng/L) | Standard Deviation 0 |
| Dose-escalation Cohort: Avelumab 20 mg/kg | Dose-escalation Cohorts: Absolute Value of Cytokine Levels | IL-4: Day 45: 48 hours After Infusion | 0.100 nanogram per liter (ng/L) | Standard Deviation 0 |
| Dose-escalation Cohort: Avelumab 20 mg/kg | Dose-escalation Cohorts: Absolute Value of Cytokine Levels | TNF-alpha: Day 15: Pre-Infusion | 2.720 nanogram per liter (ng/L) | Standard Deviation 0.969 |
| Dose-escalation Cohort: Avelumab 20 mg/kg | Dose-escalation Cohorts: Absolute Value of Cytokine Levels | IL-2: Day 1: Pre-Infusion | 0.458 nanogram per liter (ng/L) | Standard Deviation 0.472 |
| Dose-escalation Cohort: Avelumab 20 mg/kg | Dose-escalation Cohorts: Absolute Value of Cytokine Levels | IL-4: Day 43: Pre- Infusion | 0.100 nanogram per liter (ng/L) | Standard Deviation 0 |
| Dose-escalation Cohort: Avelumab 20 mg/kg | Dose-escalation Cohorts: Absolute Value of Cytokine Levels | IL-10: Day 50:168 hours After Infusion | 0.628 nanogram per liter (ng/L) | Standard Deviation 0.411 |
| Dose-escalation Cohort: Avelumab 20 mg/kg | Dose-escalation Cohorts: Absolute Value of Cytokine Levels | IL-2: Day 3: 48 hours After Infusion | 0.608 nanogram per liter (ng/L) | Standard Deviation 0.49 |
| Dose-escalation Cohort: Avelumab 20 mg/kg | Dose-escalation Cohorts: Absolute Value of Cytokine Levels | IL-6: Day 1: Pre-Infusion | 1.245 nanogram per liter (ng/L) | Standard Deviation 0.238 |
| Dose-escalation Cohort: Avelumab 20 mg/kg | Dose-escalation Cohorts: Absolute Value of Cytokine Levels | IL-4: Day 15: Pre-Infusion | 0.100 nanogram per liter (ng/L) | Standard Deviation 0 |
| Dose-escalation Cohort: Avelumab 20 mg/kg | Dose-escalation Cohorts: Absolute Value of Cytokine Levels | IL-4: Day 8: 168 hours After Infusion | 0.130 nanogram per liter (ng/L) | Standard Deviation 0.073 |
| Dose-escalation Cohort: Avelumab 20 mg/kg | Dose-escalation Cohorts: Absolute Value of Cytokine Levels | IL-8: Day 15: Pre- Infusion | 46.967 nanogram per liter (ng/L) | Standard Deviation 68.781 |
| Dose-escalation Cohort: Avelumab 20 mg/kg | Dose-escalation Cohorts: Absolute Value of Cytokine Levels | MCP-1: Day 1: Pre-Infusion | 268.415 nanogram per liter (ng/L) | Standard Deviation 52.24 |
| Dose-escalation Cohort: Avelumab 20 mg/kg | Dose-escalation Cohorts: Absolute Value of Cytokine Levels | IL-4: Day 3: 48 hours After Infusion | 0.100 nanogram per liter (ng/L) | Standard Deviation 0 |
| Dose-escalation Cohort: Avelumab 20 mg/kg | Dose-escalation Cohorts: Absolute Value of Cytokine Levels | TNF-alpha: Day 43: Pre-Infusion | 2.698 nanogram per liter (ng/L) | Standard Deviation 1.063 |
| Dose-escalation Cohort: Avelumab 20 mg/kg | Dose-escalation Cohorts: Absolute Value of Cytokine Levels | MCP-1: Day 3: 48 hours After Infusion | 276.765 nanogram per liter (ng/L) | Standard Deviation 30.402 |
| Dose-escalation Cohort: Avelumab 20 mg/kg | Dose-escalation Cohorts: Absolute Value of Cytokine Levels | IL-4: Day 1: Pre-Infusion | 0.100 nanogram per liter (ng/L) | Standard Deviation 0 |
| Dose-escalation Cohort: Avelumab 20 mg/kg | Dose-escalation Cohorts: Absolute Value of Cytokine Levels | IL-12P70: Day 50: 168 hours After Infusion | 0.348 nanogram per liter (ng/L) | Standard Deviation 0.184 |
| Dose-escalation Cohort: Avelumab 20 mg/kg | Dose-escalation Cohorts: Absolute Value of Cytokine Levels | MCP-1: Day 8: 168 hours After Infusion | 292.260 nanogram per liter (ng/L) | Standard Deviation 47.383 |
| Dose-escalation Cohort: Avelumab 20 mg/kg | Dose-escalation Cohorts: Absolute Value of Cytokine Levels | IL-2: Day 50: 168 hours After Infusion | 0.485 nanogram per liter (ng/L) | Standard Deviation 0.411 |
| Dose-escalation Cohort: Avelumab 20 mg/kg | Dose-escalation Cohorts: Absolute Value of Cytokine Levels | IL-12P70: Day 3: 48 hours After Infusion | 0.270 nanogram per liter (ng/L) | Standard Deviation 0.171 |
| Dose-escalation Cohort: Avelumab 20 mg/kg | Dose-escalation Cohorts: Absolute Value of Cytokine Levels | MCP-1: Day 15: Pre- Infusion | 267.008 nanogram per liter (ng/L) | Standard Deviation 38.395 |
| Dose-escalation Cohort: Avelumab 20 mg/kg | Dose-escalation Cohorts: Absolute Value of Cytokine Levels | IL-2: Day 45: 48 hours After Infusion | 0.488 nanogram per liter (ng/L) | Standard Deviation 0.404 |
| Dose-escalation Cohort: Avelumab 20 mg/kg | Dose-escalation Cohorts: Absolute Value of Cytokine Levels | TNF-alpha: Day 45: 48 hours After Infusion | 3.218 nanogram per liter (ng/L) | Standard Deviation 1.807 |
| Dose-escalation Cohort: Avelumab 20 mg/kg | Dose-escalation Cohorts: Absolute Value of Cytokine Levels | MCP-1: Day 43: Pre- Infusion | 228.460 nanogram per liter (ng/L) | Standard Deviation 53.309 |
| Dose-escalation Cohort: Avelumab 20 mg/kg | Dose-escalation Cohorts: Absolute Value of Cytokine Levels | IL-2: Day 43: Pre- Infusion | 0.470 nanogram per liter (ng/L) | Standard Deviation 0.362 |
| Dose-escalation Cohort: Avelumab 20 mg/kg | Dose-escalation Cohorts: Absolute Value of Cytokine Levels | IL-8: Day 45: 48 hours After Infusion | 21.300 nanogram per liter (ng/L) | Standard Deviation 7.806 |
| Dose-escalation Cohort: Avelumab 20 mg/kg | Dose-escalation Cohorts: Absolute Value of Cytokine Levels | MCP-1: Day 45: 48 hours After Infusion | 235.265 nanogram per liter (ng/L) | Standard Deviation 40.957 |
| Dose-escalation Cohort: Avelumab 20 mg/kg | Dose-escalation Cohorts: Absolute Value of Cytokine Levels | IL-8: Day 1: Pre-Infusion | 31.667 nanogram per liter (ng/L) | Standard Deviation 34.892 |
| Dose-escalation Cohort: Avelumab 20 mg/kg | Dose-escalation Cohorts: Absolute Value of Cytokine Levels | Rantes: Day 1: Pre-Infusion | 35038.29 nanogram per liter (ng/L) | Standard Deviation 6936.25 |
| Dose-escalation Cohort: Avelumab 20 mg/kg | Dose-escalation Cohorts: Absolute Value of Cytokine Levels | IL-2: Day 15: Pre-Infusion | 0.417 nanogram per liter (ng/L) | Standard Deviation 0.397 |
| Dose-escalation Cohort: Avelumab 20 mg/kg | Dose-escalation Cohorts: Absolute Value of Cytokine Levels | IL-12P70: Day 45: 48 hours After Infusion | 0.265 nanogram per liter (ng/L) | Standard Deviation 0.13 |
| Dose-escalation Cohort: Avelumab 20 mg/kg | Dose-escalation Cohorts: Absolute Value of Cytokine Levels | IFN-gamma: Day 15: Pre-Infusion | 17.998 nanogram per liter (ng/L) | Standard Deviation 18.306 |
| Dose-escalation Cohort: Avelumab 20 mg/kg | Dose-escalation Cohorts: Absolute Value of Cytokine Levels | IFN-gamma: Day 8: 168 hours After Infusion | 12.198 nanogram per liter (ng/L) | Standard Deviation 5.882 |
| Dose-escalation Cohort: Avelumab 20 mg/kg | Dose-escalation Cohorts: Absolute Value of Cytokine Levels | IL-8: Day 43: Pre-Infusion | 17.600 nanogram per liter (ng/L) | Standard Deviation 5.614 |
| Dose-escalation Cohort: Avelumab 20 mg/kg | Dose-escalation Cohorts: Absolute Value of Cytokine Levels | IFN-gamma: Day 43: Pre-Infusion | 14.863 nanogram per liter (ng/L) | Standard Deviation 13.232 |
| Dose-escalation Cohort: Avelumab 20 mg/kg | Dose-escalation Cohorts: Absolute Value of Cytokine Levels | IFN-gamma: Day 3: 48 hours After Infusion | 18.810 nanogram per liter (ng/L) | Standard Deviation 12.499 |
| Dose-escalation Cohort: Avelumab 20 mg/kg | Dose-escalation Cohorts: Absolute Value of Cytokine Levels | Rantes: Day 8: 168 hours After Infusion | 28655.39 nanogram per liter (ng/L) | Standard Deviation 8282.64 |
| Dose-escalation Cohort: Avelumab 20 mg/kg | Dose-escalation Cohorts: Absolute Value of Cytokine Levels | IL-2: Day 8: 168 hours After Infusion | 0.675 nanogram per liter (ng/L) | Standard Deviation 0.886 |
| Dose-escalation Cohort: Avelumab 20 mg/kg | Dose-escalation Cohorts: Absolute Value of Cytokine Levels | IL-12P70: Day 1: Pre-Infusion | 0.200 nanogram per liter (ng/L) | Standard Deviation 0 |
| Dose-escalation Cohort: Avelumab 20 mg/kg | Dose-escalation Cohorts: Absolute Value of Cytokine Levels | IL-8: Day 3: 48 hours After Infusion | 44.033 nanogram per liter (ng/L) | Standard Deviation 42.682 |
| Dose-escalation Cohort: Avelumab 20 mg/kg | Dose-escalation Cohorts: Absolute Value of Cytokine Levels | IL-12P70: Day 8: 168 hours After Infusion | 0.237 nanogram per liter (ng/L) | Standard Deviation 0.09 |
| Dose-escalation Cohort: Avelumab 20 mg/kg | Dose-escalation Cohorts: Absolute Value of Cytokine Levels | Rantes: Day 15: Pre-Infusion | 34758.15 nanogram per liter (ng/L) | Standard Deviation 9429.32 |
| Dose-escalation Cohort: Avelumab 20 mg/kg | Dose-escalation Cohorts: Absolute Value of Cytokine Levels | IL-10: Day 1: Pre-Infusion | 0.526 nanogram per liter (ng/L) | Standard Deviation 0.401 |
| Dose-escalation Cohort: Avelumab 20 mg/kg | Dose-escalation Cohorts: Absolute Value of Cytokine Levels | IL-1beta: Day 15: Pre- Infusion | 0.255 nanogram per liter (ng/L) | Standard Deviation 0 |
| Dose-escalation Cohort: Avelumab 20 mg/kg | Dose-escalation Cohorts: Absolute Value of Cytokine Levels | IL-10: Day 8: 168 hours After Infusion | 1.107 nanogram per liter (ng/L) | Standard Deviation 0.805 |
| Dose-escalation Cohort: Avelumab 20 mg/kg | Dose-escalation Cohorts: Absolute Value of Cytokine Levels | IFN-gamma: Day 1: Pre-Infusion | 7.723 nanogram per liter (ng/L) | Standard Deviation 2.533 |
| Dose-escalation Cohort: Avelumab 20 mg/kg | Dose-escalation Cohorts: Absolute Value of Cytokine Levels | IL-12P70: Day 43: Pre- Infusion | 0.200 nanogram per liter (ng/L) | Standard Deviation 0 |
| Dose-escalation Cohort: Avelumab 20 mg/kg | Dose-escalation Cohorts: Absolute Value of Cytokine Levels | IL-10: Day 15: Pre- Infusion | 1.045 nanogram per liter (ng/L) | Standard Deviation 0.949 |
| Dose-escalation Cohort: Avelumab 20 mg/kg | Dose-escalation Cohorts: Absolute Value of Cytokine Levels | IL-10: Day 3: 48 hours After Infusion | 0.960 nanogram per liter (ng/L) | Standard Deviation 0.634 |
| Dose-escalation Cohort: Avelumab 20 mg/kg | Dose-escalation Cohorts: Absolute Value of Cytokine Levels | Rantes: Day 43: Pre-Infusion | 36738.48 nanogram per liter (ng/L) | Standard Deviation 10865.4 |
| Dose-escalation Cohort: Avelumab 20 mg/kg | Dose-escalation Cohorts: Absolute Value of Cytokine Levels | IL-10: Day 43: Pre -Infusion | 1.248 nanogram per liter (ng/L) | Standard Deviation 1.495 |
| Dose-escalation Cohort: Avelumab 20 mg/kg | Dose-escalation Cohorts: Absolute Value of Cytokine Levels | IL-8: Day 50: 168 hours After Infusion | 19.028 nanogram per liter (ng/L) | Standard Deviation 9.162 |
| Dose-escalation Cohort: Avelumab 20 mg/kg | Dose-escalation Cohorts: Absolute Value of Cytokine Levels | IFN-gamma: Day 50: 168 hours After Infusion | 9.860 nanogram per liter (ng/L) | Standard Deviation 4.818 |
| Dose-escalation Cohort: Avelumab 20 mg/kg | Dose-escalation Cohorts: Absolute Value of Cytokine Levels | IL-10: Day 45: 48 hours After Infusion | 2.185 nanogram per liter (ng/L) | Standard Deviation 3.464 |
| Dose-escalation Cohort: Avelumab 20 mg/kg | Dose-escalation Cohorts: Absolute Value of Cytokine Levels | TNF-alpha: Day 50: 168 hours After Infusion | 2.525 nanogram per liter (ng/L) | Standard Deviation 0.965 |
| Dose-escalation Cohort: Avelumab 20 mg/kg | Dose-escalation Cohorts: Absolute Value of Cytokine Levels | IL-13: Day 1: Pre-Infusion | 1.430 nanogram per liter (ng/L) | Standard Deviation 0.637 |
| Dose-escalation Cohort: Avelumab 20 mg/kg | Dose-escalation Cohorts: Absolute Value of Cytokine Levels | TNF-alpha: Day 8: 168 hours After Infusion | 2.682 nanogram per liter (ng/L) | Standard Deviation 0.994 |
| Dose-escalation Cohort: Avelumab 20 mg/kg | Dose-escalation Cohorts: Absolute Value of Cytokine Levels | Rantes: Day 45: 48 hours After Infusion | 34107.87 nanogram per liter (ng/L) | Standard Deviation 15731.5 |
| Dose-escalation Cohort: Avelumab 20 mg/kg | Dose-escalation Cohorts: Absolute Value of Cytokine Levels | IL-13: Day 3: 48 hours After Infusion | 1.260 nanogram per liter (ng/L) | Standard Deviation 0.89 |
| Dose-escalation Cohort: Avelumab 20 mg/kg | Dose-escalation Cohorts: Absolute Value of Cytokine Levels | TNF-alpha: Day 3: 48 hours After Infusion | 3.607 nanogram per liter (ng/L) | Standard Deviation 1.579 |
| Dose-escalation Cohort: Avelumab 20 mg/kg | Dose-escalation Cohorts: Absolute Value of Cytokine Levels | IL-1beta: Day 8: 168 hours After Infusion | 0.255 nanogram per liter (ng/L) | Standard Deviation 0 |
| Dose-escalation Cohort: Avelumab 20 mg/kg | Dose-escalation Cohorts: Absolute Value of Cytokine Levels | IL-13: Day 8: 168 hours After Infusion | 1.052 nanogram per liter (ng/L) | Standard Deviation 0.586 |
| Dose-escalation Cohort: Avelumab 20 mg/kg | Dose-escalation Cohorts: Absolute Value of Cytokine Levels | Rantes: Day 3: 48 hours After Infusion | 29282.41 nanogram per liter (ng/L) | Standard Deviation 3512.35 |
| Dose-escalation Cohort: Avelumab 20 mg/kg | Dose-escalation Cohorts: Absolute Value of Cytokine Levels | IL-8: Day 8: 168 hours After Infusion | 36.500 nanogram per liter (ng/L) | Standard Deviation 40.883 |
| Dose-escalation Cohort: Avelumab 20 mg/kg | Dose-escalation Cohorts: Absolute Value of Cytokine Levels | IL-13: Day 15: Pre- Infusion | 1.032 nanogram per liter (ng/L) | Standard Deviation 0.564 |
| Dose-escalation Cohort: Avelumab 20 mg/kg | Dose-escalation Cohorts: Absolute Value of Cytokine Levels | MCP-1: Day 50: 168 hours After Infusion | 242.380 nanogram per liter (ng/L) | Standard Deviation 15.451 |
| Dose-escalation Cohort: Avelumab 20 mg/kg | Dose-escalation Cohorts: Absolute Value of Cytokine Levels | Rantes: Day 50: 168 hours After Infusion | 41265.30 nanogram per liter (ng/L) | Standard Deviation 9052.83 |
| Dose-escalation Cohort: Avelumab 20 mg/kg | Dose-escalation Cohorts: Absolute Value of Cytokine Levels | IL-13: Day 43: Pre- Infusion | 1.453 nanogram per liter (ng/L) | Standard Deviation 0.668 |
| Dose-escalation Cohort: Avelumab 20 mg/kg | Dose-escalation Cohorts: Absolute Value of Cytokine Levels | IL-6: Day 50: 168 hours After Infusion | 5.533 nanogram per liter (ng/L) | Standard Deviation 4.287 |
| Dose-escalation Cohort: Avelumab 20 mg/kg | Dose-escalation Cohorts: Absolute Value of Cytokine Levels | IL-12P70: Day 15: Pre- Infusion | 0.200 nanogram per liter (ng/L) | Standard Deviation 0 |
| Dose-escalation Cohort: Avelumab 20 mg/kg | Dose-escalation Cohorts: Absolute Value of Cytokine Levels | IL-6: Day 45: 48 hours After Infusion | 3.065 nanogram per liter (ng/L) | Standard Deviation 2.355 |
| Dose-escalation Cohort: Avelumab 20 mg/kg | Dose-escalation Cohorts: Absolute Value of Cytokine Levels | TNF-alpha: Day 1: Pre-Infusion | 2.188 nanogram per liter (ng/L) | Standard Deviation 0.65 |
| Dose-escalation Cohort: Avelumab 20 mg/kg | Dose-escalation Cohorts: Absolute Value of Cytokine Levels | IL-13: Day 50:168 hours After Infusion 4 | 0.985 nanogram per liter (ng/L) | Standard Deviation 0.534 |
| Dose-escalation Cohort: Avelumab 20 mg/kg | Dose-escalation Cohorts: Absolute Value of Cytokine Levels | IL-6: Day 43: Pre- Infusion | 2.995 nanogram per liter (ng/L) | Standard Deviation 2.5 |
Secondary
Dose-escalation Cohorts: Area Under the Serum Concentration-Time Curve From the Time of Dosing to the Time of the Last Observation (AUC0-t) of Avelumab
Area under the serum concentration vs time curve from time zero to the last sampling time t at which the concentration was at or above the lower limit of quantification (LLOQ). AUC0-t was calculated by linear trapezoidal summation.
Time frame: Within 6 hours before the infusion, at end of 1-hour infusion (Day 1), 0.5, 1, 2, 4, 6,12, 24, 36, 48, 168 hours after end of infusion
Population: Pharmacokinetic (PK) analysis set included all participants who have received at least 1 dose of study treatment and provided at least 1 measurable post-dose concentration.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Dose-escalation Cohort: Avelumab 3 mg/kg | Dose-escalation Cohorts: Area Under the Serum Concentration-Time Curve From the Time of Dosing to the Time of the Last Observation (AUC0-t) of Avelumab | 5120 hour*microgram per milliliter(hr*mcg/mL) | Geometric Coefficient of Variation 32.5 |
| Dose-escalation Cohort: Avelumab 10 mg/kg | Dose-escalation Cohorts: Area Under the Serum Concentration-Time Curve From the Time of Dosing to the Time of the Last Observation (AUC0-t) of Avelumab | 20100 hour*microgram per milliliter(hr*mcg/mL) | Geometric Coefficient of Variation 40 |
| Dose-escalation Cohort: Avelumab 20 mg/kg | Dose-escalation Cohorts: Area Under the Serum Concentration-Time Curve From the Time of Dosing to the Time of the Last Observation (AUC0-t) of Avelumab | 46800 hour*microgram per milliliter(hr*mcg/mL) | Geometric Coefficient of Variation 23.1 |
Secondary
Dose-escalation Cohorts: Area Under the Serum Concentration-Time Curve From Time Zero Extrapolated to Infinity (AUC0-inf) of Avelumab
Area under the curve from the time of dosing extrapolated to infinity was calculated by the linear trapezoidal summation and extrapolated to infinity using Clast/Lambda z after the first intravenous infusion. Clast was the last quantifiable concentration and Lambda z was terminal elimination rate constant determined by log-linear regression analysis of the measured serum concentrations of the terminal log-linear phase.
Time frame: Within 6 hours before the infusion, at end of 1-hour infusion (Day 1), 0.5, 1, 2, 4, 6,12, 24, 36, 48, 168 hours after end of infusion
Population: PK analysis set included all participants who have received at least 1 dose of study treatment and provided at least 1 measurable post-dose concentration.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Dose-escalation Cohort: Avelumab 3 mg/kg | Dose-escalation Cohorts: Area Under the Serum Concentration-Time Curve From Time Zero Extrapolated to Infinity (AUC0-inf) of Avelumab | 6040 hr*mcg/mL | Geometric Coefficient of Variation 27.5 |
| Dose-escalation Cohort: Avelumab 10 mg/kg | Dose-escalation Cohorts: Area Under the Serum Concentration-Time Curve From Time Zero Extrapolated to Infinity (AUC0-inf) of Avelumab | 24000 hr*mcg/mL | Geometric Coefficient of Variation 47.4 |
| Dose-escalation Cohort: Avelumab 20 mg/kg | Dose-escalation Cohorts: Area Under the Serum Concentration-Time Curve From Time Zero Extrapolated to Infinity (AUC0-inf) of Avelumab | 53700 hr*mcg/mL | Geometric Coefficient of Variation 24.3 |
Secondary
Dose-escalation Cohorts: Log Fold Change From Baseline in Cytokine Levels
Cytokine analysis was performed to evaluate levels of Rantes, Monocyte chemoattractant protein-1 (MCP-1) and various interleukins (including IL-1beta, IL-2, IL-4, IL-6, IL-10, IL-12p70, IL-13, IL-8), Tumor necrosis factors-alpha (TNF-alpha) and Interferon-gamma (IFN-gamma) in serum samples. Log fold change from baseline (logFC) was defined as logFC (cytokine at time t) = log (cytokine signal at time t) - log (cytokine signal at baseline).
Time frame: Baseline (Day 1 [Pre-infusion]), Day 3 (48 hours after infusion), Day 8 (168 hours after infusion), Day 15 (Pre-infusion), Day 43 (Pre-infusion), Day 45 (48 hours after infusion), Day 50 (168 hours after infusion)
Population: Safety analysis set included all participants who have received at least 1 dose of study treatment. Here number analyzed signified those participants who were evaluable for this outcome measure at the specified time points for the given category.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Dose-escalation Cohort: Avelumab 3 mg/kg | Dose-escalation Cohorts: Log Fold Change From Baseline in Cytokine Levels | IL-4: Day 50: 168 hours After Infusion | 0.000 log fold change | Standard Deviation 0 |
| Dose-escalation Cohort: Avelumab 3 mg/kg | Dose-escalation Cohorts: Log Fold Change From Baseline in Cytokine Levels | IL-8: Day 3: 48 hours After Infusion | 0.604 log fold change | Standard Deviation 0.553 |
| Dose-escalation Cohort: Avelumab 3 mg/kg | Dose-escalation Cohorts: Log Fold Change From Baseline in Cytokine Levels | IL-6: Day 3: 48 hours After Infusion | 0.153 log fold change | Standard Deviation 0.897 |
| Dose-escalation Cohort: Avelumab 3 mg/kg | Dose-escalation Cohorts: Log Fold Change From Baseline in Cytokine Levels | MCP-1: Day 8: 168 hours After Infusion | 0.067 log fold change | Standard Deviation 0.278 |
| Dose-escalation Cohort: Avelumab 3 mg/kg | Dose-escalation Cohorts: Log Fold Change From Baseline in Cytokine Levels | IFN-gamma: Day 15: Pre-Infusion | 0.396 log fold change | Standard Deviation 1.958 |
| Dose-escalation Cohort: Avelumab 3 mg/kg | Dose-escalation Cohorts: Log Fold Change From Baseline in Cytokine Levels | IL-6: Day 8: 168 hours After Infusion | 0.314 log fold change | Standard Deviation 0.421 |
| Dose-escalation Cohort: Avelumab 3 mg/kg | Dose-escalation Cohorts: Log Fold Change From Baseline in Cytokine Levels | IL-13: Day 15: Pre- Infusion | -0.133 log fold change | Standard Deviation 1.191 |
| Dose-escalation Cohort: Avelumab 3 mg/kg | Dose-escalation Cohorts: Log Fold Change From Baseline in Cytokine Levels | IFN-gamma: Day 3: 48 hours After Infusion | 0.903 log fold change | Standard Deviation 1.258 |
| Dose-escalation Cohort: Avelumab 3 mg/kg | Dose-escalation Cohorts: Log Fold Change From Baseline in Cytokine Levels | IL-6: Day 15: Pre- Infusion | 0.069 log fold change | Standard Deviation 1.455 |
| Dose-escalation Cohort: Avelumab 3 mg/kg | Dose-escalation Cohorts: Log Fold Change From Baseline in Cytokine Levels | IL-6: Day 43: Pre- Infusion | 0.068 log fold change | Standard Deviation 0.949 |
| Dose-escalation Cohort: Avelumab 3 mg/kg | Dose-escalation Cohorts: Log Fold Change From Baseline in Cytokine Levels | IL-12P70: Day 50: 168 hours After Infusion | 0.000 log fold change | Standard Deviation 0 |
| Dose-escalation Cohort: Avelumab 3 mg/kg | Dose-escalation Cohorts: Log Fold Change From Baseline in Cytokine Levels | IL-8: Day 50: 168 hours After Infusion | 0.924 log fold change | Standard Deviation 1.088 |
| Dose-escalation Cohort: Avelumab 3 mg/kg | Dose-escalation Cohorts: Log Fold Change From Baseline in Cytokine Levels | IL-6: Day 50: 168 hours After Infusion | 0.064 log fold change | Standard Deviation 0.573 |
| Dose-escalation Cohort: Avelumab 3 mg/kg | Dose-escalation Cohorts: Log Fold Change From Baseline in Cytokine Levels | MCP-1: Day 3: 48 hours After Infusion | 0.242 log fold change | Standard Deviation 0.206 |
| Dose-escalation Cohort: Avelumab 3 mg/kg | Dose-escalation Cohorts: Log Fold Change From Baseline in Cytokine Levels | IL-6: Day 45: 48 hours After Infusion | 0.273 log fold change | Standard Deviation 1.187 |
| Dose-escalation Cohort: Avelumab 3 mg/kg | Dose-escalation Cohorts: Log Fold Change From Baseline in Cytokine Levels | IL-13: Day 45: 48 hours After Infusion | 0.769 log fold change | Standard Deviation 1.778 |
| Dose-escalation Cohort: Avelumab 3 mg/kg | Dose-escalation Cohorts: Log Fold Change From Baseline in Cytokine Levels | IFN-gamma: Day 8: 168 hours After Infusion | 0.280 log fold change | Standard Deviation 1.365 |
| Dose-escalation Cohort: Avelumab 3 mg/kg | Dose-escalation Cohorts: Log Fold Change From Baseline in Cytokine Levels | IL-8: Day 15: Pre- Infusion | 0.201 log fold change | Standard Deviation 0.56 |
| Dose-escalation Cohort: Avelumab 3 mg/kg | Dose-escalation Cohorts: Log Fold Change From Baseline in Cytokine Levels | MCP-1: Day 50: 168 hours After Infusion | 0.144 log fold change | Standard Deviation 0.226 |
| Dose-escalation Cohort: Avelumab 3 mg/kg | Dose-escalation Cohorts: Log Fold Change From Baseline in Cytokine Levels | IL-4: Day 45: 48 hours After Infusion | 0.000 log fold change | Standard Deviation 0 |
| Dose-escalation Cohort: Avelumab 3 mg/kg | Dose-escalation Cohorts: Log Fold Change From Baseline in Cytokine Levels | IL-8: Day 8: 168 hours After Infusion | 0.444 log fold change | Standard Deviation 0.313 |
| Dose-escalation Cohort: Avelumab 3 mg/kg | Dose-escalation Cohorts: Log Fold Change From Baseline in Cytokine Levels | Rantes: Day 3: 48 hours After Infusion | 0.198 log fold change | Standard Deviation 0.849 |
| Dose-escalation Cohort: Avelumab 3 mg/kg | Dose-escalation Cohorts: Log Fold Change From Baseline in Cytokine Levels | IL-13: Day 50:168 hours After Infusion 4 | 0.867 log fold change | Standard Deviation 1.796 |
| Dose-escalation Cohort: Avelumab 3 mg/kg | Dose-escalation Cohorts: Log Fold Change From Baseline in Cytokine Levels | TNF-alpha: Day 45: 48 hours After Infusion | 0.612 log fold change | Standard Deviation 0.848 |
| Dose-escalation Cohort: Avelumab 3 mg/kg | Dose-escalation Cohorts: Log Fold Change From Baseline in Cytokine Levels | TNF-alpha: Day 50: 168 hours After Infusion | 0.400 log fold change | Standard Deviation 0.672 |
| Dose-escalation Cohort: Avelumab 3 mg/kg | Dose-escalation Cohorts: Log Fold Change From Baseline in Cytokine Levels | TNF-alpha: Day 43: Pre-Infusion | 0.329 log fold change | Standard Deviation 0.253 |
| Dose-escalation Cohort: Avelumab 3 mg/kg | Dose-escalation Cohorts: Log Fold Change From Baseline in Cytokine Levels | Rantes: Day 15: Pre-Infusion | 0.997 log fold change | Standard Deviation 1.992 |
| Dose-escalation Cohort: Avelumab 3 mg/kg | Dose-escalation Cohorts: Log Fold Change From Baseline in Cytokine Levels | IL-4: Day 8: 168 hours After Infusion | 0.000 log fold change | Standard Deviation 0 |
| Dose-escalation Cohort: Avelumab 3 mg/kg | Dose-escalation Cohorts: Log Fold Change From Baseline in Cytokine Levels | TNF-alpha: Day 15: Pre-Infusion | 0.182 log fold change | Standard Deviation 0.805 |
| Dose-escalation Cohort: Avelumab 3 mg/kg | Dose-escalation Cohorts: Log Fold Change From Baseline in Cytokine Levels | Rantes: Day 43: Pre-Infusion | 0.389 log fold change | Standard Deviation 1.452 |
| Dose-escalation Cohort: Avelumab 3 mg/kg | Dose-escalation Cohorts: Log Fold Change From Baseline in Cytokine Levels | IL-1beta: Day 3: 48 hours After Infusion | 0.000 log fold change | Standard Deviation 0 |
| Dose-escalation Cohort: Avelumab 3 mg/kg | Dose-escalation Cohorts: Log Fold Change From Baseline in Cytokine Levels | TNF-alpha: Day 8: 168 hours After Infusion | 0.065 log fold change | Standard Deviation 0.378 |
| Dose-escalation Cohort: Avelumab 3 mg/kg | Dose-escalation Cohorts: Log Fold Change From Baseline in Cytokine Levels | Rantes: Day 45: 48 hours After Infusion | 0.249 log fold change | Standard Deviation 1.947 |
| Dose-escalation Cohort: Avelumab 3 mg/kg | Dose-escalation Cohorts: Log Fold Change From Baseline in Cytokine Levels | IL-8: Day 45: 48 hours After Infusion | 0.858 log fold change | Standard Deviation 0.885 |
| Dose-escalation Cohort: Avelumab 3 mg/kg | Dose-escalation Cohorts: Log Fold Change From Baseline in Cytokine Levels | Rantes: Day 50: 168 hours After Infusion | 0.718 log fold change | Standard Deviation 1.386 |
| Dose-escalation Cohort: Avelumab 3 mg/kg | Dose-escalation Cohorts: Log Fold Change From Baseline in Cytokine Levels | IL-2: Day 8: 168 hours After Infusion | -0.118 log fold change | Standard Deviation 1.23 |
| Dose-escalation Cohort: Avelumab 3 mg/kg | Dose-escalation Cohorts: Log Fold Change From Baseline in Cytokine Levels | IL-1beta: Day 8: 168 hours After Infusion | 0.000 log fold change | Standard Deviation 0 |
| Dose-escalation Cohort: Avelumab 3 mg/kg | Dose-escalation Cohorts: Log Fold Change From Baseline in Cytokine Levels | TNF-alpha: Day 3: 48 hours After Infusion | 0.589 log fold change | Standard Deviation 0.443 |
| Dose-escalation Cohort: Avelumab 3 mg/kg | Dose-escalation Cohorts: Log Fold Change From Baseline in Cytokine Levels | IL-1beta: Day 50: 168 hours After Infusion | 0.000 log fold change | Standard Deviation 0 |
| Dose-escalation Cohort: Avelumab 3 mg/kg | Dose-escalation Cohorts: Log Fold Change From Baseline in Cytokine Levels | IL-1beta: Day 15: Pre- Infusion | 0.000 log fold change | Standard Deviation 0 |
| Dose-escalation Cohort: Avelumab 3 mg/kg | Dose-escalation Cohorts: Log Fold Change From Baseline in Cytokine Levels | IL-10: Day 8: 168 hours After Infusion | 0.624 log fold change | Standard Deviation 1.081 |
| Dose-escalation Cohort: Avelumab 3 mg/kg | Dose-escalation Cohorts: Log Fold Change From Baseline in Cytokine Levels | IL-1beta: Day 45: 48 hours After Infusion | 0.000 log fold change | Standard Deviation 0 |
| Dose-escalation Cohort: Avelumab 3 mg/kg | Dose-escalation Cohorts: Log Fold Change From Baseline in Cytokine Levels | IL-1beta: Day 43: Pre-Infusion | 0.000 log fold change | Standard Deviation 0 |
| Dose-escalation Cohort: Avelumab 3 mg/kg | Dose-escalation Cohorts: Log Fold Change From Baseline in Cytokine Levels | Rantes: Day 8: 168 hours After Infusion | 0.289 log fold change | Standard Deviation 1.709 |
| Dose-escalation Cohort: Avelumab 3 mg/kg | Dose-escalation Cohorts: Log Fold Change From Baseline in Cytokine Levels | IL-13: Day 43: Pre- Infusion | 0.353 log fold change | Standard Deviation 1.67 |
| Dose-escalation Cohort: Avelumab 3 mg/kg | Dose-escalation Cohorts: Log Fold Change From Baseline in Cytokine Levels | IL-10: Day 45: 48 hours After Infusion | 0.976 log fold change | Standard Deviation 1.416 |
| Dose-escalation Cohort: Avelumab 3 mg/kg | Dose-escalation Cohorts: Log Fold Change From Baseline in Cytokine Levels | IL-10: Day 43: Pre-Infusion | 0.919 log fold change | Standard Deviation 0.736 |
| Dose-escalation Cohort: Avelumab 3 mg/kg | Dose-escalation Cohorts: Log Fold Change From Baseline in Cytokine Levels | MCP-1: Day 45: 48 hours After Infusion | 0.045 log fold change | Standard Deviation 0.209 |
| Dose-escalation Cohort: Avelumab 3 mg/kg | Dose-escalation Cohorts: Log Fold Change From Baseline in Cytokine Levels | IL-10: Day 15: Pre- Infusion | 0.972 log fold change | Standard Deviation 0.691 |
| Dose-escalation Cohort: Avelumab 3 mg/kg | Dose-escalation Cohorts: Log Fold Change From Baseline in Cytokine Levels | IL-2: Day 3: 48 hours After Infusion | 0.108 log fold change | Standard Deviation 1.34 |
| Dose-escalation Cohort: Avelumab 3 mg/kg | Dose-escalation Cohorts: Log Fold Change From Baseline in Cytokine Levels | IL-10: Day 50:168 hours After Infusion | 0.633 log fold change | Standard Deviation 1.122 |
| Dose-escalation Cohort: Avelumab 3 mg/kg | Dose-escalation Cohorts: Log Fold Change From Baseline in Cytokine Levels | IL-10: Day 3: 48 hours After Infusion | 1.103 log fold change | Standard Deviation 0.888 |
| Dose-escalation Cohort: Avelumab 3 mg/kg | Dose-escalation Cohorts: Log Fold Change From Baseline in Cytokine Levels | IL-2: Day 15: Pre-Infusion | -0.228 log fold change | Standard Deviation 1.134 |
| Dose-escalation Cohort: Avelumab 3 mg/kg | Dose-escalation Cohorts: Log Fold Change From Baseline in Cytokine Levels | IFN-gamma: Day 45: 48 hours After Infusion | 0.768 log fold change | Standard Deviation 1.925 |
| Dose-escalation Cohort: Avelumab 3 mg/kg | Dose-escalation Cohorts: Log Fold Change From Baseline in Cytokine Levels | IL-12P70: Day 45: 48 hours After Infusion | 0.000 log fold change | Standard Deviation 0 |
| Dose-escalation Cohort: Avelumab 3 mg/kg | Dose-escalation Cohorts: Log Fold Change From Baseline in Cytokine Levels | IL-2: Day 43: Pre- Infusion | 0.296 log fold change | Standard Deviation 1.375 |
| Dose-escalation Cohort: Avelumab 3 mg/kg | Dose-escalation Cohorts: Log Fold Change From Baseline in Cytokine Levels | MCP-1: Day 43: Pre- Infusion | 0.173 log fold change | Standard Deviation 0.358 |
| Dose-escalation Cohort: Avelumab 3 mg/kg | Dose-escalation Cohorts: Log Fold Change From Baseline in Cytokine Levels | IL-12P70: Day 43: Pre- Infusion | 0.000 log fold change | Standard Deviation 0 |
| Dose-escalation Cohort: Avelumab 3 mg/kg | Dose-escalation Cohorts: Log Fold Change From Baseline in Cytokine Levels | IL-2: Day 45: 48 hours After Infusion | 0.194 log fold change | Standard Deviation 1.675 |
| Dose-escalation Cohort: Avelumab 3 mg/kg | Dose-escalation Cohorts: Log Fold Change From Baseline in Cytokine Levels | IL-13: Day 3: 48 hours After Infusion | -0.541 log fold change | Standard Deviation 0.98 |
| Dose-escalation Cohort: Avelumab 3 mg/kg | Dose-escalation Cohorts: Log Fold Change From Baseline in Cytokine Levels | IL-12P70: Day 15: Pre- Infusion | 0.000 log fold change | Standard Deviation 0 |
| Dose-escalation Cohort: Avelumab 3 mg/kg | Dose-escalation Cohorts: Log Fold Change From Baseline in Cytokine Levels | IL-2: Day 50: 168 hours After Infusion | 0.432 log fold change | Standard Deviation 1.547 |
| Dose-escalation Cohort: Avelumab 3 mg/kg | Dose-escalation Cohorts: Log Fold Change From Baseline in Cytokine Levels | IL-8: Day 43: Pre-Infusion | 0.773 log fold change | Standard Deviation 1.073 |
| Dose-escalation Cohort: Avelumab 3 mg/kg | Dose-escalation Cohorts: Log Fold Change From Baseline in Cytokine Levels | IL-12P70: Day 8: 168 hours After Infusion | 0.000 log fold change | Standard Deviation 0 |
| Dose-escalation Cohort: Avelumab 3 mg/kg | Dose-escalation Cohorts: Log Fold Change From Baseline in Cytokine Levels | IL-4: Day 3: 48 hours After Infusion | 0.000 log fold change | Standard Deviation 0 |
| Dose-escalation Cohort: Avelumab 3 mg/kg | Dose-escalation Cohorts: Log Fold Change From Baseline in Cytokine Levels | MCP-1: Day 15: Pre- Infusion | -0.010 log fold change | Standard Deviation 0.684 |
| Dose-escalation Cohort: Avelumab 3 mg/kg | Dose-escalation Cohorts: Log Fold Change From Baseline in Cytokine Levels | IL-12P70: Day 3: 48 hours After Infusion | 0.000 log fold change | Standard Deviation 0 |
| Dose-escalation Cohort: Avelumab 3 mg/kg | Dose-escalation Cohorts: Log Fold Change From Baseline in Cytokine Levels | IL-4: Day 15: Pre-Infusion | 0.000 log fold change | Standard Deviation 0 |
| Dose-escalation Cohort: Avelumab 3 mg/kg | Dose-escalation Cohorts: Log Fold Change From Baseline in Cytokine Levels | IL-13: Day 8: 168 hours After Infusion | 0.407 log fold change | Standard Deviation 0.896 |
| Dose-escalation Cohort: Avelumab 3 mg/kg | Dose-escalation Cohorts: Log Fold Change From Baseline in Cytokine Levels | IFN-gamma: Day 50: 168 hours After Infusion | 0.234 log fold change | Standard Deviation 1.385 |
| Dose-escalation Cohort: Avelumab 3 mg/kg | Dose-escalation Cohorts: Log Fold Change From Baseline in Cytokine Levels | IFN-gamma: Day 43: Pre-Infusion | 0.071 log fold change | Standard Deviation 0.8 |
| Dose-escalation Cohort: Avelumab 3 mg/kg | Dose-escalation Cohorts: Log Fold Change From Baseline in Cytokine Levels | IL-4: Day 43: Pre- Infusion | 0.000 log fold change | Standard Deviation 0 |
| Dose-escalation Cohort: Avelumab 10 mg/kg | Dose-escalation Cohorts: Log Fold Change From Baseline in Cytokine Levels | IL-8: Day 50: 168 hours After Infusion | 0.441 log fold change | Standard Deviation 0.284 |
| Dose-escalation Cohort: Avelumab 10 mg/kg | Dose-escalation Cohorts: Log Fold Change From Baseline in Cytokine Levels | IL-12P70: Day 50: 168 hours After Infusion | 0.151 log fold change | Standard Deviation 1.033 |
| Dose-escalation Cohort: Avelumab 10 mg/kg | Dose-escalation Cohorts: Log Fold Change From Baseline in Cytokine Levels | IL-10: Day 3: 48 hours After Infusion | 0.743 log fold change | Standard Deviation 0.371 |
| Dose-escalation Cohort: Avelumab 10 mg/kg | Dose-escalation Cohorts: Log Fold Change From Baseline in Cytokine Levels | IL-10: Day 50:168 hours After Infusion | 1.041 log fold change | Standard Deviation 1.68 |
| Dose-escalation Cohort: Avelumab 10 mg/kg | Dose-escalation Cohorts: Log Fold Change From Baseline in Cytokine Levels | IL-13: Day 3: 48 hours After Infusion | -0.170 log fold change | Standard Deviation 0.844 |
| Dose-escalation Cohort: Avelumab 10 mg/kg | Dose-escalation Cohorts: Log Fold Change From Baseline in Cytokine Levels | IL-13: Day 8: 168 hours After Infusion | -0.004 log fold change | Standard Deviation 0.245 |
| Dose-escalation Cohort: Avelumab 10 mg/kg | Dose-escalation Cohorts: Log Fold Change From Baseline in Cytokine Levels | IL-13: Day 15: Pre- Infusion | 0.125 log fold change | Standard Deviation 0.467 |
| Dose-escalation Cohort: Avelumab 10 mg/kg | Dose-escalation Cohorts: Log Fold Change From Baseline in Cytokine Levels | IL-13: Day 45: 48 hours After Infusion | -0.327 log fold change | Standard Deviation 0.729 |
| Dose-escalation Cohort: Avelumab 10 mg/kg | Dose-escalation Cohorts: Log Fold Change From Baseline in Cytokine Levels | IL-13: Day 50:168 hours After Infusion 4 | -0.427 log fold change | Standard Deviation 1.082 |
| Dose-escalation Cohort: Avelumab 10 mg/kg | Dose-escalation Cohorts: Log Fold Change From Baseline in Cytokine Levels | IL-1beta: Day 3: 48 hours After Infusion | 0.000 log fold change | Standard Deviation 0 |
| Dose-escalation Cohort: Avelumab 10 mg/kg | Dose-escalation Cohorts: Log Fold Change From Baseline in Cytokine Levels | IL-1beta: Day 8: 168 hours After Infusion | 0.278 log fold change | Standard Deviation 0.681 |
| Dose-escalation Cohort: Avelumab 10 mg/kg | Dose-escalation Cohorts: Log Fold Change From Baseline in Cytokine Levels | IL-1beta: Day 15: Pre- Infusion | 0.000 log fold change | Standard Deviation 0 |
| Dose-escalation Cohort: Avelumab 10 mg/kg | Dose-escalation Cohorts: Log Fold Change From Baseline in Cytokine Levels | IL-1beta: Day 43: Pre-Infusion | 0.303 log fold change | Standard Deviation 0.743 |
| Dose-escalation Cohort: Avelumab 10 mg/kg | Dose-escalation Cohorts: Log Fold Change From Baseline in Cytokine Levels | IL-2: Day 8: 168 hours After Infusion | 0.035 log fold change | Standard Deviation 0.906 |
| Dose-escalation Cohort: Avelumab 10 mg/kg | Dose-escalation Cohorts: Log Fold Change From Baseline in Cytokine Levels | IL-2: Day 3: 48 hours After Infusion | 0.664 log fold change | Standard Deviation 0.749 |
| Dose-escalation Cohort: Avelumab 10 mg/kg | Dose-escalation Cohorts: Log Fold Change From Baseline in Cytokine Levels | IL-2: Day 15: Pre-Infusion | -0.577 log fold change | Standard Deviation 1.055 |
| Dose-escalation Cohort: Avelumab 10 mg/kg | Dose-escalation Cohorts: Log Fold Change From Baseline in Cytokine Levels | IL-2: Day 43: Pre- Infusion | 0.211 log fold change | Standard Deviation 0.754 |
| Dose-escalation Cohort: Avelumab 10 mg/kg | Dose-escalation Cohorts: Log Fold Change From Baseline in Cytokine Levels | IL-2: Day 45: 48 hours After Infusion | 0.009 log fold change | Standard Deviation 0.892 |
| Dose-escalation Cohort: Avelumab 10 mg/kg | Dose-escalation Cohorts: Log Fold Change From Baseline in Cytokine Levels | IL-2: Day 50: 168 hours After Infusion | 0.099 log fold change | Standard Deviation 0.608 |
| Dose-escalation Cohort: Avelumab 10 mg/kg | Dose-escalation Cohorts: Log Fold Change From Baseline in Cytokine Levels | IL-4: Day 8: 168 hours After Infusion | 0.000 log fold change | Standard Deviation 0 |
| Dose-escalation Cohort: Avelumab 10 mg/kg | Dose-escalation Cohorts: Log Fold Change From Baseline in Cytokine Levels | IL-4: Day 15: Pre-Infusion | 0.000 log fold change | Standard Deviation 0 |
| Dose-escalation Cohort: Avelumab 10 mg/kg | Dose-escalation Cohorts: Log Fold Change From Baseline in Cytokine Levels | IL-4: Day 50: 168 hours After Infusion | 0.000 log fold change | Standard Deviation 0 |
| Dose-escalation Cohort: Avelumab 10 mg/kg | Dose-escalation Cohorts: Log Fold Change From Baseline in Cytokine Levels | IL-6: Day 3: 48 hours After Infusion | 0.660 log fold change | Standard Deviation 0.816 |
| Dose-escalation Cohort: Avelumab 10 mg/kg | Dose-escalation Cohorts: Log Fold Change From Baseline in Cytokine Levels | IL-6: Day 8: 168 hours After Infusion | 0.194 log fold change | Standard Deviation 0.618 |
| Dose-escalation Cohort: Avelumab 10 mg/kg | Dose-escalation Cohorts: Log Fold Change From Baseline in Cytokine Levels | IL-6: Day 43: Pre- Infusion | -0.009 log fold change | Standard Deviation 0.98 |
| Dose-escalation Cohort: Avelumab 10 mg/kg | Dose-escalation Cohorts: Log Fold Change From Baseline in Cytokine Levels | IL-6: Day 45: 48 hours After Infusion | 0.116 log fold change | Standard Deviation 0.676 |
| Dose-escalation Cohort: Avelumab 10 mg/kg | Dose-escalation Cohorts: Log Fold Change From Baseline in Cytokine Levels | MCP-1: Day 3: 48 hours After Infusion | 0.213 log fold change | Standard Deviation 0.296 |
| Dose-escalation Cohort: Avelumab 10 mg/kg | Dose-escalation Cohorts: Log Fold Change From Baseline in Cytokine Levels | MCP-1: Day 43: Pre- Infusion | 0.055 log fold change | Standard Deviation 0.343 |
| Dose-escalation Cohort: Avelumab 10 mg/kg | Dose-escalation Cohorts: Log Fold Change From Baseline in Cytokine Levels | MCP-1: Day 45: 48 hours After Infusion | 0.318 log fold change | Standard Deviation 0.383 |
| Dose-escalation Cohort: Avelumab 10 mg/kg | Dose-escalation Cohorts: Log Fold Change From Baseline in Cytokine Levels | MCP-1: Day 50: 168 hours After Infusion | 0.180 log fold change | Standard Deviation 0.394 |
| Dose-escalation Cohort: Avelumab 10 mg/kg | Dose-escalation Cohorts: Log Fold Change From Baseline in Cytokine Levels | Rantes: Day 3: 48 hours After Infusion | 0.589 log fold change | Standard Deviation 0.927 |
| Dose-escalation Cohort: Avelumab 10 mg/kg | Dose-escalation Cohorts: Log Fold Change From Baseline in Cytokine Levels | Rantes: Day 8: 168 hours After Infusion | 0.615 log fold change | Standard Deviation 0.866 |
| Dose-escalation Cohort: Avelumab 10 mg/kg | Dose-escalation Cohorts: Log Fold Change From Baseline in Cytokine Levels | Rantes: Day 15: Pre-Infusion | 0.582 log fold change | Standard Deviation 0.649 |
| Dose-escalation Cohort: Avelumab 10 mg/kg | Dose-escalation Cohorts: Log Fold Change From Baseline in Cytokine Levels | Rantes: Day 43: Pre-Infusion | 0.450 log fold change | Standard Deviation 0.765 |
| Dose-escalation Cohort: Avelumab 10 mg/kg | Dose-escalation Cohorts: Log Fold Change From Baseline in Cytokine Levels | Rantes: Day 45: 48 hours After Infusion | 0.353 log fold change | Standard Deviation 0.809 |
| Dose-escalation Cohort: Avelumab 10 mg/kg | Dose-escalation Cohorts: Log Fold Change From Baseline in Cytokine Levels | Rantes: Day 50: 168 hours After Infusion | 0.656 log fold change | Standard Deviation 0.634 |
| Dose-escalation Cohort: Avelumab 10 mg/kg | Dose-escalation Cohorts: Log Fold Change From Baseline in Cytokine Levels | TNF-alpha: Day 3: 48 hours After Infusion | 0.770 log fold change | Standard Deviation 0.314 |
| Dose-escalation Cohort: Avelumab 10 mg/kg | Dose-escalation Cohorts: Log Fold Change From Baseline in Cytokine Levels | TNF-alpha: Day 8: 168 hours After Infusion | 0.343 log fold change | Standard Deviation 0.195 |
| Dose-escalation Cohort: Avelumab 10 mg/kg | Dose-escalation Cohorts: Log Fold Change From Baseline in Cytokine Levels | IL-8: Day 3: 48 hours After Infusion | 0.539 log fold change | Standard Deviation 0.4 |
| Dose-escalation Cohort: Avelumab 10 mg/kg | Dose-escalation Cohorts: Log Fold Change From Baseline in Cytokine Levels | TNF-alpha: Day 15: Pre-Infusion | 0.301 log fold change | Standard Deviation 0.09 |
| Dose-escalation Cohort: Avelumab 10 mg/kg | Dose-escalation Cohorts: Log Fold Change From Baseline in Cytokine Levels | TNF-alpha: Day 43: Pre-Infusion | 0.365 log fold change | Standard Deviation 0.304 |
| Dose-escalation Cohort: Avelumab 10 mg/kg | Dose-escalation Cohorts: Log Fold Change From Baseline in Cytokine Levels | TNF-alpha: Day 45: 48 hours After Infusion | 0.527 log fold change | Standard Deviation 0.376 |
| Dose-escalation Cohort: Avelumab 10 mg/kg | Dose-escalation Cohorts: Log Fold Change From Baseline in Cytokine Levels | IL-8: Day 8: 168 hours After Infusion | 0.393 log fold change | Standard Deviation 0.406 |
| Dose-escalation Cohort: Avelumab 10 mg/kg | Dose-escalation Cohorts: Log Fold Change From Baseline in Cytokine Levels | IL-8: Day 43: Pre-Infusion | 0.241 log fold change | Standard Deviation 0.388 |
| Dose-escalation Cohort: Avelumab 10 mg/kg | Dose-escalation Cohorts: Log Fold Change From Baseline in Cytokine Levels | IL-8: Day 45: 48 hours After Infusion | 0.451 log fold change | Standard Deviation 0.33 |
| Dose-escalation Cohort: Avelumab 10 mg/kg | Dose-escalation Cohorts: Log Fold Change From Baseline in Cytokine Levels | IFN-gamma: Day 3: 48 hours After Infusion | 1.038 log fold change | Standard Deviation 0.689 |
| Dose-escalation Cohort: Avelumab 10 mg/kg | Dose-escalation Cohorts: Log Fold Change From Baseline in Cytokine Levels | IFN-gamma: Day 8: 168 hours After Infusion | 0.722 log fold change | Standard Deviation 0.945 |
| Dose-escalation Cohort: Avelumab 10 mg/kg | Dose-escalation Cohorts: Log Fold Change From Baseline in Cytokine Levels | IFN-gamma: Day 15: Pre-Infusion | 0.779 log fold change | Standard Deviation 0.654 |
| Dose-escalation Cohort: Avelumab 10 mg/kg | Dose-escalation Cohorts: Log Fold Change From Baseline in Cytokine Levels | IFN-gamma: Day 43: Pre-Infusion | 1.335 log fold change | Standard Deviation 1.735 |
| Dose-escalation Cohort: Avelumab 10 mg/kg | Dose-escalation Cohorts: Log Fold Change From Baseline in Cytokine Levels | IFN-gamma: Day 45: 48 hours After Infusion | 1.617 log fold change | Standard Deviation 2.037 |
| Dose-escalation Cohort: Avelumab 10 mg/kg | Dose-escalation Cohorts: Log Fold Change From Baseline in Cytokine Levels | IFN-gamma: Day 50: 168 hours After Infusion | 1.045 log fold change | Standard Deviation 2.01 |
| Dose-escalation Cohort: Avelumab 10 mg/kg | Dose-escalation Cohorts: Log Fold Change From Baseline in Cytokine Levels | IL-12P70: Day 3: 48 hours After Infusion | -0.030 log fold change | Standard Deviation 0.75 |
| Dose-escalation Cohort: Avelumab 10 mg/kg | Dose-escalation Cohorts: Log Fold Change From Baseline in Cytokine Levels | IL-12P70: Day 8: 168 hours After Infusion | -0.203 log fold change | Standard Deviation 0.504 |
| Dose-escalation Cohort: Avelumab 10 mg/kg | Dose-escalation Cohorts: Log Fold Change From Baseline in Cytokine Levels | IL-12P70: Day 15: Pre- Infusion | -0.174 log fold change | Standard Deviation 0.524 |
| Dose-escalation Cohort: Avelumab 10 mg/kg | Dose-escalation Cohorts: Log Fold Change From Baseline in Cytokine Levels | IL-12P70: Day 43: Pre- Infusion | 0.239 log fold change | Standard Deviation 0.99 |
| Dose-escalation Cohort: Avelumab 10 mg/kg | Dose-escalation Cohorts: Log Fold Change From Baseline in Cytokine Levels | IL-12P70: Day 45: 48 hours After Infusion | 0.087 log fold change | Standard Deviation 0.95 |
| Dose-escalation Cohort: Avelumab 10 mg/kg | Dose-escalation Cohorts: Log Fold Change From Baseline in Cytokine Levels | IL-10: Day 8: 168 hours After Infusion | 0.704 log fold change | Standard Deviation 0.962 |
| Dose-escalation Cohort: Avelumab 10 mg/kg | Dose-escalation Cohorts: Log Fold Change From Baseline in Cytokine Levels | IL-10: Day 15: Pre- Infusion | 0.720 log fold change | Standard Deviation 0.978 |
| Dose-escalation Cohort: Avelumab 10 mg/kg | Dose-escalation Cohorts: Log Fold Change From Baseline in Cytokine Levels | IL-10: Day 43: Pre-Infusion | 1.072 log fold change | Standard Deviation 1.452 |
| Dose-escalation Cohort: Avelumab 10 mg/kg | Dose-escalation Cohorts: Log Fold Change From Baseline in Cytokine Levels | IL-10: Day 45: 48 hours After Infusion | 1.375 log fold change | Standard Deviation 1.767 |
| Dose-escalation Cohort: Avelumab 10 mg/kg | Dose-escalation Cohorts: Log Fold Change From Baseline in Cytokine Levels | IL-13: Day 43: Pre- Infusion | -0.044 log fold change | Standard Deviation 0.866 |
| Dose-escalation Cohort: Avelumab 10 mg/kg | Dose-escalation Cohorts: Log Fold Change From Baseline in Cytokine Levels | IL-1beta: Day 45: 48 hours After Infusion | 0.493 log fold change | Standard Deviation 1.207 |
| Dose-escalation Cohort: Avelumab 10 mg/kg | Dose-escalation Cohorts: Log Fold Change From Baseline in Cytokine Levels | IL-1beta: Day 50: 168 hours After Infusion | 0.473 log fold change | Standard Deviation 1.158 |
| Dose-escalation Cohort: Avelumab 10 mg/kg | Dose-escalation Cohorts: Log Fold Change From Baseline in Cytokine Levels | IL-4: Day 3: 48 hours After Infusion | 0.000 log fold change | Standard Deviation 0 |
| Dose-escalation Cohort: Avelumab 10 mg/kg | Dose-escalation Cohorts: Log Fold Change From Baseline in Cytokine Levels | IL-4: Day 43: Pre- Infusion | 0.000 log fold change | Standard Deviation 0 |
| Dose-escalation Cohort: Avelumab 10 mg/kg | Dose-escalation Cohorts: Log Fold Change From Baseline in Cytokine Levels | IL-4: Day 45: 48 hours After Infusion | 0.000 log fold change | Standard Deviation 0 |
| Dose-escalation Cohort: Avelumab 10 mg/kg | Dose-escalation Cohorts: Log Fold Change From Baseline in Cytokine Levels | IL-6: Day 15: Pre- Infusion | 0.451 log fold change | Standard Deviation 1.457 |
| Dose-escalation Cohort: Avelumab 10 mg/kg | Dose-escalation Cohorts: Log Fold Change From Baseline in Cytokine Levels | IL-6: Day 50: 168 hours After Infusion | 0.279 log fold change | Standard Deviation 0.69 |
| Dose-escalation Cohort: Avelumab 10 mg/kg | Dose-escalation Cohorts: Log Fold Change From Baseline in Cytokine Levels | MCP-1: Day 8: 168 hours After Infusion | 0.110 log fold change | Standard Deviation 0.297 |
| Dose-escalation Cohort: Avelumab 10 mg/kg | Dose-escalation Cohorts: Log Fold Change From Baseline in Cytokine Levels | MCP-1: Day 15: Pre- Infusion | 0.120 log fold change | Standard Deviation 0.141 |
| Dose-escalation Cohort: Avelumab 10 mg/kg | Dose-escalation Cohorts: Log Fold Change From Baseline in Cytokine Levels | TNF-alpha: Day 50: 168 hours After Infusion | 0.507 log fold change | Standard Deviation 0.378 |
| Dose-escalation Cohort: Avelumab 10 mg/kg | Dose-escalation Cohorts: Log Fold Change From Baseline in Cytokine Levels | IL-8: Day 15: Pre- Infusion | 0.118 log fold change | Standard Deviation 0.467 |
| Dose-escalation Cohort: Avelumab 20 mg/kg | Dose-escalation Cohorts: Log Fold Change From Baseline in Cytokine Levels | IL-4: Day 50: 168 hours After Infusion | 0.000 log fold change | Standard Deviation 0 |
| Dose-escalation Cohort: Avelumab 20 mg/kg | Dose-escalation Cohorts: Log Fold Change From Baseline in Cytokine Levels | IL-6: Day 45: 48 hours After Infusion | 1.158 log fold change | Standard Deviation 0.998 |
| Dose-escalation Cohort: Avelumab 20 mg/kg | Dose-escalation Cohorts: Log Fold Change From Baseline in Cytokine Levels | IL-13: Day 15: Pre- Infusion | -0.603 log fold change | Standard Deviation 0.519 |
| Dose-escalation Cohort: Avelumab 20 mg/kg | Dose-escalation Cohorts: Log Fold Change From Baseline in Cytokine Levels | IFN-gamma: Day 45: 48 hours After Infusion | 1.215 log fold change | Standard Deviation 1.576 |
| Dose-escalation Cohort: Avelumab 20 mg/kg | Dose-escalation Cohorts: Log Fold Change From Baseline in Cytokine Levels | IL-4: Day 15: Pre-Infusion | 0.000 log fold change | Standard Deviation 0 |
| Dose-escalation Cohort: Avelumab 20 mg/kg | Dose-escalation Cohorts: Log Fold Change From Baseline in Cytokine Levels | IL-12P70: Day 45: 48 hours After Infusion | 0.300 log fold change | Standard Deviation 0.601 |
| Dose-escalation Cohort: Avelumab 20 mg/kg | Dose-escalation Cohorts: Log Fold Change From Baseline in Cytokine Levels | IL-4: Day 8: 168 hours After Infusion | 0.248 log fold change | Standard Deviation 0.606 |
| Dose-escalation Cohort: Avelumab 20 mg/kg | Dose-escalation Cohorts: Log Fold Change From Baseline in Cytokine Levels | IL-6: Day 50: 168 hours After Infusion | 1.883 log fold change | Standard Deviation 1.287 |
| Dose-escalation Cohort: Avelumab 20 mg/kg | Dose-escalation Cohorts: Log Fold Change From Baseline in Cytokine Levels | IL-12P70: Day 3: 48 hours After Infusion | 0.272 log fold change | Standard Deviation 0.666 |
| Dose-escalation Cohort: Avelumab 20 mg/kg | Dose-escalation Cohorts: Log Fold Change From Baseline in Cytokine Levels | IL-2: Day 50: 168 hours After Infusion | -0.188 log fold change | Standard Deviation 0.22 |
| Dose-escalation Cohort: Avelumab 20 mg/kg | Dose-escalation Cohorts: Log Fold Change From Baseline in Cytokine Levels | MCP-1: Day 3: 48 hours After Infusion | 0.062 log fold change | Standard Deviation 0.234 |
| Dose-escalation Cohort: Avelumab 20 mg/kg | Dose-escalation Cohorts: Log Fold Change From Baseline in Cytokine Levels | IL-12P70: Day 8: 168 hours After Infusion | 0.178 log fold change | Standard Deviation 0.437 |
| Dose-escalation Cohort: Avelumab 20 mg/kg | Dose-escalation Cohorts: Log Fold Change From Baseline in Cytokine Levels | IL-2: Day 45: 48 hours After Infusion | -0.175 log fold change | Standard Deviation 0.202 |
| Dose-escalation Cohort: Avelumab 20 mg/kg | Dose-escalation Cohorts: Log Fold Change From Baseline in Cytokine Levels | IL-13: Day 8: 168 hours After Infusion | -0.581 log fold change | Standard Deviation 0.49 |
| Dose-escalation Cohort: Avelumab 20 mg/kg | Dose-escalation Cohorts: Log Fold Change From Baseline in Cytokine Levels | IL-12P70: Day 15: Pre- Infusion | 0.000 log fold change | Standard Deviation 0 |
| Dose-escalation Cohort: Avelumab 20 mg/kg | Dose-escalation Cohorts: Log Fold Change From Baseline in Cytokine Levels | IL-2: Day 43: Pre- Infusion | -0.193 log fold change | Standard Deviation 0.243 |
| Dose-escalation Cohort: Avelumab 20 mg/kg | Dose-escalation Cohorts: Log Fold Change From Baseline in Cytokine Levels | IFN-gamma: Day 43: Pre-Infusion | 0.631 log fold change | Standard Deviation 0.593 |
| Dose-escalation Cohort: Avelumab 20 mg/kg | Dose-escalation Cohorts: Log Fold Change From Baseline in Cytokine Levels | IL-12P70: Day 43: Pre- Infusion | 0.000 log fold change | Standard Deviation 0 |
| Dose-escalation Cohort: Avelumab 20 mg/kg | Dose-escalation Cohorts: Log Fold Change From Baseline in Cytokine Levels | IL-2: Day 15: Pre-Infusion | -0.059 log fold change | Standard Deviation 0.096 |
| Dose-escalation Cohort: Avelumab 20 mg/kg | Dose-escalation Cohorts: Log Fold Change From Baseline in Cytokine Levels | MCP-1: Day 8: 168 hours After Infusion | 0.132 log fold change | Standard Deviation 0.202 |
| Dose-escalation Cohort: Avelumab 20 mg/kg | Dose-escalation Cohorts: Log Fold Change From Baseline in Cytokine Levels | IL-2: Day 3: 48 hours After Infusion | 0.531 log fold change | Standard Deviation 0.628 |
| Dose-escalation Cohort: Avelumab 20 mg/kg | Dose-escalation Cohorts: Log Fold Change From Baseline in Cytokine Levels | IL-13: Day 3: 48 hours After Infusion | -0.416 log fold change | Standard Deviation 1.245 |
| Dose-escalation Cohort: Avelumab 20 mg/kg | Dose-escalation Cohorts: Log Fold Change From Baseline in Cytokine Levels | IL-1beta: Day 50: 168 hours After Infusion | 0.000 log fold change | Standard Deviation 0 |
| Dose-escalation Cohort: Avelumab 20 mg/kg | Dose-escalation Cohorts: Log Fold Change From Baseline in Cytokine Levels | IL-8: Day 15: Pre- Infusion | 0.256 log fold change | Standard Deviation 0.536 |
| Dose-escalation Cohort: Avelumab 20 mg/kg | Dose-escalation Cohorts: Log Fold Change From Baseline in Cytokine Levels | IL-10: Day 15: Pre- Infusion | 0.942 log fold change | Standard Deviation 0.444 |
| Dose-escalation Cohort: Avelumab 20 mg/kg | Dose-escalation Cohorts: Log Fold Change From Baseline in Cytokine Levels | IL-1beta: Day 45: 48 hours After Infusion | 0.000 log fold change | Standard Deviation 0 |
| Dose-escalation Cohort: Avelumab 20 mg/kg | Dose-escalation Cohorts: Log Fold Change From Baseline in Cytokine Levels | MCP-1: Day 15: Pre- Infusion | 0.005 log fold change | Standard Deviation 0.211 |
| Dose-escalation Cohort: Avelumab 20 mg/kg | Dose-escalation Cohorts: Log Fold Change From Baseline in Cytokine Levels | IL-10: Day 43: Pre-Infusion | 1.317 log fold change | Standard Deviation 1.238 |
| Dose-escalation Cohort: Avelumab 20 mg/kg | Dose-escalation Cohorts: Log Fold Change From Baseline in Cytokine Levels | IL-2: Day 8: 168 hours After Infusion | 0.326 log fold change | Standard Deviation 0.545 |
| Dose-escalation Cohort: Avelumab 20 mg/kg | Dose-escalation Cohorts: Log Fold Change From Baseline in Cytokine Levels | IL-10: Day 50:168 hours After Infusion | 0.761 log fold change | Standard Deviation 0.713 |
| Dose-escalation Cohort: Avelumab 20 mg/kg | Dose-escalation Cohorts: Log Fold Change From Baseline in Cytokine Levels | IL-1beta: Day 43: Pre-Infusion | 0.000 log fold change | Standard Deviation 0 |
| Dose-escalation Cohort: Avelumab 20 mg/kg | Dose-escalation Cohorts: Log Fold Change From Baseline in Cytokine Levels | MCP-1: Day 43: Pre- Infusion | -0.232 log fold change | Standard Deviation 0.15 |
| Dose-escalation Cohort: Avelumab 20 mg/kg | Dose-escalation Cohorts: Log Fold Change From Baseline in Cytokine Levels | IL-1beta: Day 15: Pre- Infusion | 0.000 log fold change | Standard Deviation 0 |
| Dose-escalation Cohort: Avelumab 20 mg/kg | Dose-escalation Cohorts: Log Fold Change From Baseline in Cytokine Levels | IL-10: Day 45: 48 hours After Infusion | 1.467 log fold change | Standard Deviation 1.758 |
| Dose-escalation Cohort: Avelumab 20 mg/kg | Dose-escalation Cohorts: Log Fold Change From Baseline in Cytokine Levels | IL-1beta: Day 8: 168 hours After Infusion | 0.000 log fold change | Standard Deviation 0 |
| Dose-escalation Cohort: Avelumab 20 mg/kg | Dose-escalation Cohorts: Log Fold Change From Baseline in Cytokine Levels | Rantes: Day 45: 48 hours After Infusion | -0.257 log fold change | Standard Deviation 0.487 |
| Dose-escalation Cohort: Avelumab 20 mg/kg | Dose-escalation Cohorts: Log Fold Change From Baseline in Cytokine Levels | IL-10: Day 8: 168 hours After Infusion | 1.088 log fold change | Standard Deviation 0.348 |
| Dose-escalation Cohort: Avelumab 20 mg/kg | Dose-escalation Cohorts: Log Fold Change From Baseline in Cytokine Levels | Rantes: Day 50: 168 hours After Infusion | 0.107 log fold change | Standard Deviation 0.326 |
| Dose-escalation Cohort: Avelumab 20 mg/kg | Dose-escalation Cohorts: Log Fold Change From Baseline in Cytokine Levels | IL-1beta: Day 3: 48 hours After Infusion | 0.275 log fold change | Standard Deviation 0.673 |
| Dose-escalation Cohort: Avelumab 20 mg/kg | Dose-escalation Cohorts: Log Fold Change From Baseline in Cytokine Levels | TNF-alpha: Day 3: 48 hours After Infusion | 0.646 log fold change | Standard Deviation 0.388 |
| Dose-escalation Cohort: Avelumab 20 mg/kg | Dose-escalation Cohorts: Log Fold Change From Baseline in Cytokine Levels | Rantes: Day 43: Pre-Infusion | -0.079 log fold change | Standard Deviation 0.306 |
| Dose-escalation Cohort: Avelumab 20 mg/kg | Dose-escalation Cohorts: Log Fold Change From Baseline in Cytokine Levels | IL-10: Day 3: 48 hours After Infusion | 0.942 log fold change | Standard Deviation 0.199 |
| Dose-escalation Cohort: Avelumab 20 mg/kg | Dose-escalation Cohorts: Log Fold Change From Baseline in Cytokine Levels | IL-4: Day 3: 48 hours After Infusion | 0.000 log fold change | Standard Deviation 0 |
| Dose-escalation Cohort: Avelumab 20 mg/kg | Dose-escalation Cohorts: Log Fold Change From Baseline in Cytokine Levels | TNF-alpha: Day 8: 168 hours After Infusion | 0.262 log fold change | Standard Deviation 0.144 |
| Dose-escalation Cohort: Avelumab 20 mg/kg | Dose-escalation Cohorts: Log Fold Change From Baseline in Cytokine Levels | Rantes: Day 15: Pre-Infusion | -0.025 log fold change | Standard Deviation 0.36 |
| Dose-escalation Cohort: Avelumab 20 mg/kg | Dose-escalation Cohorts: Log Fold Change From Baseline in Cytokine Levels | IL-13: Day 50:168 hours After Infusion 4 | -0.319 log fold change | Standard Deviation 0.615 |
| Dose-escalation Cohort: Avelumab 20 mg/kg | Dose-escalation Cohorts: Log Fold Change From Baseline in Cytokine Levels | TNF-alpha: Day 15: Pre-Infusion | 0.292 log fold change | Standard Deviation 0.158 |
| Dose-escalation Cohort: Avelumab 20 mg/kg | Dose-escalation Cohorts: Log Fold Change From Baseline in Cytokine Levels | Rantes: Day 8: 168 hours After Infusion | -0.325 log fold change | Standard Deviation 0.625 |
| Dose-escalation Cohort: Avelumab 20 mg/kg | Dose-escalation Cohorts: Log Fold Change From Baseline in Cytokine Levels | IL-12P70: Day 50: 168 hours After Infusion | 0.643 log fold change | Standard Deviation 0.77 |
| Dose-escalation Cohort: Avelumab 20 mg/kg | Dose-escalation Cohorts: Log Fold Change From Baseline in Cytokine Levels | TNF-alpha: Day 43: Pre-Infusion | 0.216 log fold change | Standard Deviation 0.184 |
| Dose-escalation Cohort: Avelumab 20 mg/kg | Dose-escalation Cohorts: Log Fold Change From Baseline in Cytokine Levels | Rantes: Day 3: 48 hours After Infusion | -0.242 log fold change | Standard Deviation 0.383 |
| Dose-escalation Cohort: Avelumab 20 mg/kg | Dose-escalation Cohorts: Log Fold Change From Baseline in Cytokine Levels | IL-4: Day 43: Pre- Infusion | 0.000 log fold change | Standard Deviation 0 |
| Dose-escalation Cohort: Avelumab 20 mg/kg | Dose-escalation Cohorts: Log Fold Change From Baseline in Cytokine Levels | TNF-alpha: Day 45: 48 hours After Infusion | 0.382 log fold change | Standard Deviation 0.422 |
| Dose-escalation Cohort: Avelumab 20 mg/kg | Dose-escalation Cohorts: Log Fold Change From Baseline in Cytokine Levels | IL-8: Day 3: 48 hours After Infusion | 0.554 log fold change | Standard Deviation 0.484 |
| Dose-escalation Cohort: Avelumab 20 mg/kg | Dose-escalation Cohorts: Log Fold Change From Baseline in Cytokine Levels | MCP-1: Day 50: 168 hours After Infusion | -0.118 log fold change | Standard Deviation 0.42 |
| Dose-escalation Cohort: Avelumab 20 mg/kg | Dose-escalation Cohorts: Log Fold Change From Baseline in Cytokine Levels | IL-13: Day 45: 48 hours After Infusion | -0.660 log fold change | Standard Deviation 0.56 |
| Dose-escalation Cohort: Avelumab 20 mg/kg | Dose-escalation Cohorts: Log Fold Change From Baseline in Cytokine Levels | IL-8: Day 8: 168 hours After Infusion | 0.189 log fold change | Standard Deviation 0.145 |
| Dose-escalation Cohort: Avelumab 20 mg/kg | Dose-escalation Cohorts: Log Fold Change From Baseline in Cytokine Levels | MCP-1: Day 45: 48 hours After Infusion | -0.176 log fold change | Standard Deviation 0.183 |
| Dose-escalation Cohort: Avelumab 20 mg/kg | Dose-escalation Cohorts: Log Fold Change From Baseline in Cytokine Levels | IFN-gamma: Day 50: 168 hours After Infusion | 0.273 log fold change | Standard Deviation 0.249 |
| Dose-escalation Cohort: Avelumab 20 mg/kg | Dose-escalation Cohorts: Log Fold Change From Baseline in Cytokine Levels | IL-8: Day 43: Pre-Infusion | 0.033 log fold change | Standard Deviation 0.367 |
| Dose-escalation Cohort: Avelumab 20 mg/kg | Dose-escalation Cohorts: Log Fold Change From Baseline in Cytokine Levels | IL-4: Day 45: 48 hours After Infusion | 0.000 log fold change | Standard Deviation 0 |
| Dose-escalation Cohort: Avelumab 20 mg/kg | Dose-escalation Cohorts: Log Fold Change From Baseline in Cytokine Levels | IL-8: Day 45: 48 hours After Infusion | 0.283 log fold change | Standard Deviation 0.499 |
| Dose-escalation Cohort: Avelumab 20 mg/kg | Dose-escalation Cohorts: Log Fold Change From Baseline in Cytokine Levels | IL-6: Day 43: Pre- Infusion | 1.112 log fold change | Standard Deviation 0.898 |
| Dose-escalation Cohort: Avelumab 20 mg/kg | Dose-escalation Cohorts: Log Fold Change From Baseline in Cytokine Levels | IL-6: Day 8: 168 hours After Infusion | 0.498 log fold change | Standard Deviation 0.321 |
| Dose-escalation Cohort: Avelumab 20 mg/kg | Dose-escalation Cohorts: Log Fold Change From Baseline in Cytokine Levels | IL-8: Day 50: 168 hours After Infusion | 0.081 log fold change | Standard Deviation 0.798 |
| Dose-escalation Cohort: Avelumab 20 mg/kg | Dose-escalation Cohorts: Log Fold Change From Baseline in Cytokine Levels | TNF-alpha: Day 50: 168 hours After Infusion | 0.119 log fold change | Standard Deviation 0.134 |
| Dose-escalation Cohort: Avelumab 20 mg/kg | Dose-escalation Cohorts: Log Fold Change From Baseline in Cytokine Levels | IFN-gamma: Day 3: 48 hours After Infusion | 1.096 log fold change | Standard Deviation 0.975 |
| Dose-escalation Cohort: Avelumab 20 mg/kg | Dose-escalation Cohorts: Log Fold Change From Baseline in Cytokine Levels | IL-6: Day 15: Pre- Infusion | 0.474 log fold change | Standard Deviation 0.572 |
| Dose-escalation Cohort: Avelumab 20 mg/kg | Dose-escalation Cohorts: Log Fold Change From Baseline in Cytokine Levels | IFN-gamma: Day 8: 168 hours After Infusion | 0.600 log fold change | Standard Deviation 0.243 |
| Dose-escalation Cohort: Avelumab 20 mg/kg | Dose-escalation Cohorts: Log Fold Change From Baseline in Cytokine Levels | IL-6: Day 3: 48 hours After Infusion | 1.196 log fold change | Standard Deviation 1.614 |
| Dose-escalation Cohort: Avelumab 20 mg/kg | Dose-escalation Cohorts: Log Fold Change From Baseline in Cytokine Levels | IL-13: Day 43: Pre- Infusion | 0.200 log fold change | Standard Deviation 0.391 |
| Dose-escalation Cohort: Avelumab 20 mg/kg | Dose-escalation Cohorts: Log Fold Change From Baseline in Cytokine Levels | IFN-gamma: Day 15: Pre-Infusion | 0.867 log fold change | Standard Deviation 0.69 |
Secondary
Dose-escalation Cohorts: Maximum Observed Serum Concentration (Cmax) of Avelumab
Cmax was obtained directly from the concentration versus time curve.
Time frame: Within 6 hours before the infusion, at end of 1-hour infusion (Day 1), 0.5, 1, 2, 4, 6,12, 24, 36, 48, 168 hours after end of infusion
Population: PK analysis set included all participants who have received at least 1 dose of study treatment and provided at least 1 measurable post-dose concentration.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Dose-escalation Cohort: Avelumab 3 mg/kg | Dose-escalation Cohorts: Maximum Observed Serum Concentration (Cmax) of Avelumab | 64 mcg/mL | Geometric Coefficient of Variation 22.2 |
| Dose-escalation Cohort: Avelumab 10 mg/kg | Dose-escalation Cohorts: Maximum Observed Serum Concentration (Cmax) of Avelumab | 179 mcg/mL | Geometric Coefficient of Variation 19.6 |
| Dose-escalation Cohort: Avelumab 20 mg/kg | Dose-escalation Cohorts: Maximum Observed Serum Concentration (Cmax) of Avelumab | 459 mcg/mL | Geometric Coefficient of Variation 13.6 |
Secondary
Dose-escalation Cohorts: Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs, TEAEs Leading to Death, and TEAEs Leading to Discontinuation
An Adverse Event (AE) was defined as any unfavourable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of study drug, whether or not considered related to the study drug or worsening of pre-existing medical condition, whether or not related to study drug. A serious adverse event (SAE) was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect or was otherwise considered medically important. TEAEs were those events with onset dates occurring during the on-treatment period for the first time, or if the worsening of an event was during the on-treatment period. TEAEs included both serious TEAEs and non-serious TEAEs.
Time frame: Time from first dose of study treatment up to 2205 days
Population: Safety analysis set included all participants who have received at least 1 dose of study treatment.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Dose-escalation Cohort: Avelumab 3 mg/kg | Dose-escalation Cohorts: Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs, TEAEs Leading to Death, and TEAEs Leading to Discontinuation | TEAEs | 5 Participants |
| Dose-escalation Cohort: Avelumab 3 mg/kg | Dose-escalation Cohorts: Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs, TEAEs Leading to Death, and TEAEs Leading to Discontinuation | Serious TEAEs | 1 Participants |
| Dose-escalation Cohort: Avelumab 3 mg/kg | Dose-escalation Cohorts: Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs, TEAEs Leading to Death, and TEAEs Leading to Discontinuation | TEAEs Leading To Discontinuation | 0 Participants |
| Dose-escalation Cohort: Avelumab 3 mg/kg | Dose-escalation Cohorts: Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs, TEAEs Leading to Death, and TEAEs Leading to Discontinuation | TEAEs Leading To Death | 1 Participants |
| Dose-escalation Cohort: Avelumab 10 mg/kg | Dose-escalation Cohorts: Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs, TEAEs Leading to Death, and TEAEs Leading to Discontinuation | TEAEs Leading To Death | 0 Participants |
| Dose-escalation Cohort: Avelumab 10 mg/kg | Dose-escalation Cohorts: Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs, TEAEs Leading to Death, and TEAEs Leading to Discontinuation | TEAEs | 6 Participants |
| Dose-escalation Cohort: Avelumab 10 mg/kg | Dose-escalation Cohorts: Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs, TEAEs Leading to Death, and TEAEs Leading to Discontinuation | TEAEs Leading To Discontinuation | 0 Participants |
| Dose-escalation Cohort: Avelumab 10 mg/kg | Dose-escalation Cohorts: Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs, TEAEs Leading to Death, and TEAEs Leading to Discontinuation | Serious TEAEs | 0 Participants |
| Dose-escalation Cohort: Avelumab 20 mg/kg | Dose-escalation Cohorts: Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs, TEAEs Leading to Death, and TEAEs Leading to Discontinuation | TEAEs | 5 Participants |
| Dose-escalation Cohort: Avelumab 20 mg/kg | Dose-escalation Cohorts: Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs, TEAEs Leading to Death, and TEAEs Leading to Discontinuation | TEAEs Leading To Death | 0 Participants |
| Dose-escalation Cohort: Avelumab 20 mg/kg | Dose-escalation Cohorts: Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs, TEAEs Leading to Death, and TEAEs Leading to Discontinuation | Serious TEAEs | 2 Participants |
| Dose-escalation Cohort: Avelumab 20 mg/kg | Dose-escalation Cohorts: Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs, TEAEs Leading to Death, and TEAEs Leading to Discontinuation | TEAEs Leading To Discontinuation | 1 Participants |
Secondary
Dose-escalation Cohorts: Number of Participants With Treatment-Emergent Positive Human Anti-Human Antibody (HAHA)
Participants not having positive HAHA prior to treatment with Avelumab and with at least one positive post-baseline result in the HAHA assay were termed as treatment-emergent. Treatment-emergent participants were further classified as Transient Positive or Persistent positive. Participants were considered as transient positive if time between first and last positive result was less than 16 weeks apart and a negative result at the most recent visit. Participants were considered as persistent positive if time between first and last positive result greater than or equal to \[\>=\] 16 weeks apart or a positive evaluation at the most recent visit. Number of participants with treatment-emergent positive HAHA were reported.
Time frame: Day 15 up to Day 2205
Population: Safety analysis set included all participants who have received at least 1 dose of study treatment.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Dose-escalation Cohort: Avelumab 3 mg/kg | Dose-escalation Cohorts: Number of Participants With Treatment-Emergent Positive Human Anti-Human Antibody (HAHA) | Transient positive treatment emergent | 0 Participants |
| Dose-escalation Cohort: Avelumab 3 mg/kg | Dose-escalation Cohorts: Number of Participants With Treatment-Emergent Positive Human Anti-Human Antibody (HAHA) | Persistent positive treatment emergent | 1 Participants |
| Dose-escalation Cohort: Avelumab 10 mg/kg | Dose-escalation Cohorts: Number of Participants With Treatment-Emergent Positive Human Anti-Human Antibody (HAHA) | Transient positive treatment emergent | 0 Participants |
| Dose-escalation Cohort: Avelumab 10 mg/kg | Dose-escalation Cohorts: Number of Participants With Treatment-Emergent Positive Human Anti-Human Antibody (HAHA) | Persistent positive treatment emergent | 0 Participants |
| Dose-escalation Cohort: Avelumab 20 mg/kg | Dose-escalation Cohorts: Number of Participants With Treatment-Emergent Positive Human Anti-Human Antibody (HAHA) | Transient positive treatment emergent | 0 Participants |
| Dose-escalation Cohort: Avelumab 20 mg/kg | Dose-escalation Cohorts: Number of Participants With Treatment-Emergent Positive Human Anti-Human Antibody (HAHA) | Persistent positive treatment emergent | 0 Participants |
Secondary
Dose-escalation Cohorts: Programmed Death Ligand 1 (PD-L1) Receptor Occupancy
Percentage of PD-L1 receptors occupied by avelumab on human lymphocytes (CD3+ 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.
Time frame: Pre-infusion on Day 1; 4 and 48 hours after infusion on Day 3; Pre-infusion on Days 15, 29, 43, and 85
Population: Safety analysis set included all participants who have received at least 1 dose of study treatment.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Dose-escalation Cohort: Avelumab 3 mg/kg | Dose-escalation Cohorts: Programmed Death Ligand 1 (PD-L1) Receptor Occupancy | NA percentage of receptors |
| Dose-escalation Cohort: Avelumab 10 mg/kg | Dose-escalation Cohorts: Programmed Death Ligand 1 (PD-L1) Receptor Occupancy | NA percentage of receptors |
| Dose-escalation Cohort: Avelumab 20 mg/kg | Dose-escalation Cohorts: Programmed Death Ligand 1 (PD-L1) Receptor Occupancy | NA percentage of receptors |
Secondary
Dose-escalation Cohorts: Terminal Elimination Rate Constant (Lambda z) of Avelumab
Terminal elimination rate constant was determined by log-linear regression analysis of the measured serum concentrations of the terminal log-linear phase. Participant wise data was reported for this outcome measure.
Time frame: Within 6 hours before the infusion, at end of 1-hour infusion (Day 1), 0.5, 1, 2, 4, 6,12, 24, 36, 48, 168 hours after end of infusion
Population: PK analysis set included all participants who have received at least 1 dose of study treatment and provided at least 1 measurable post-dose concentration. The summarized data was not available for these arms therefore individual data was presented. Here, Number Analyzed signifies specific participant evaluated in respective arm.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Dose-escalation Cohort: Avelumab 3 mg/kg | Dose-escalation Cohorts: Terminal Elimination Rate Constant (Lambda z) of Avelumab | Participant 4 | 0.00663 per hour |
| Dose-escalation Cohort: Avelumab 3 mg/kg | Dose-escalation Cohorts: Terminal Elimination Rate Constant (Lambda z) of Avelumab | Participant 5 | 0.00501 per hour |
| Dose-escalation Cohort: Avelumab 3 mg/kg | Dose-escalation Cohorts: Terminal Elimination Rate Constant (Lambda z) of Avelumab | Participant 2 | 0.0114 per hour |
| Dose-escalation Cohort: Avelumab 3 mg/kg | Dose-escalation Cohorts: Terminal Elimination Rate Constant (Lambda z) of Avelumab | Participant 1 | 0.00667 per hour |
| Dose-escalation Cohort: Avelumab 3 mg/kg | Dose-escalation Cohorts: Terminal Elimination Rate Constant (Lambda z) of Avelumab | Participant 3 | 0.00868 per hour |
| Dose-escalation Cohort: Avelumab 10 mg/kg | Dose-escalation Cohorts: Terminal Elimination Rate Constant (Lambda z) of Avelumab | Participant 1 | 0.0103 per hour |
| Dose-escalation Cohort: Avelumab 10 mg/kg | Dose-escalation Cohorts: Terminal Elimination Rate Constant (Lambda z) of Avelumab | Participant 2 | 0.00456 per hour |
| Dose-escalation Cohort: Avelumab 10 mg/kg | Dose-escalation Cohorts: Terminal Elimination Rate Constant (Lambda z) of Avelumab | Participant 4 | 0.00508 per hour |
| Dose-escalation Cohort: Avelumab 10 mg/kg | Dose-escalation Cohorts: Terminal Elimination Rate Constant (Lambda z) of Avelumab | Participant 6 | 0.00662 per hour |
| Dose-escalation Cohort: Avelumab 10 mg/kg | Dose-escalation Cohorts: Terminal Elimination Rate Constant (Lambda z) of Avelumab | Participant 3 | 0.00456 per hour |
| Dose-escalation Cohort: Avelumab 10 mg/kg | Dose-escalation Cohorts: Terminal Elimination Rate Constant (Lambda z) of Avelumab | Participant 5 | 0.00476 per hour |
| Dose-escalation Cohort: Avelumab 20 mg/kg | Dose-escalation Cohorts: Terminal Elimination Rate Constant (Lambda z) of Avelumab | Participant 6 | 0.00562 per hour |
| Dose-escalation Cohort: Avelumab 20 mg/kg | Dose-escalation Cohorts: Terminal Elimination Rate Constant (Lambda z) of Avelumab | Participant 1 | 0.00568 per hour |
| Dose-escalation Cohort: Avelumab 20 mg/kg | Dose-escalation Cohorts: Terminal Elimination Rate Constant (Lambda z) of Avelumab | Participant 2 | 0.00750 per hour |
| Dose-escalation Cohort: Avelumab 20 mg/kg | Dose-escalation Cohorts: Terminal Elimination Rate Constant (Lambda z) of Avelumab | Participant 3 | 0.00604 per hour |
| Dose-escalation Cohort: Avelumab 20 mg/kg | Dose-escalation Cohorts: Terminal Elimination Rate Constant (Lambda z) of Avelumab | Participant 4 | 0.00568 per hour |
| Dose-escalation Cohort: Avelumab 20 mg/kg | Dose-escalation Cohorts: Terminal Elimination Rate Constant (Lambda z) of Avelumab | Participant 5 | 0.00666 per hour |
Secondary
Dose-escalation Cohorts: Terminal Half-Life (t1/2) of Avelumab
t1/2 was the time measured for the concentration to decrease by one half, determined as 0.693/Lambda z, here Lambda z was the terminal elimination rate constant determined by log-linear regression analysis of the measured serum concentrations of the terminal log-linear phase.
Time frame: Within 6 hours before the infusion, at end of 1-hour infusion (Day 1), 0.5, 1, 2, 4, 6,12, 24, 36, 48, 168 hours after end of infusion
Population: PK analysis set included all participants who have received at least 1 dose of study treatment and provided at least 1 measurable post-dose concentration.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Dose-escalation Cohort: Avelumab 3 mg/kg | Dose-escalation Cohorts: Terminal Half-Life (t1/2) of Avelumab | 94 hour | Geometric Coefficient of Variation 31.7 |
| Dose-escalation Cohort: Avelumab 10 mg/kg | Dose-escalation Cohorts: Terminal Half-Life (t1/2) of Avelumab | 122 hour | Geometric Coefficient of Variation 33.1 |
| Dose-escalation Cohort: Avelumab 20 mg/kg | Dose-escalation Cohorts: Terminal Half-Life (t1/2) of Avelumab | 112 hour | Geometric Coefficient of Variation 11.6 |
Secondary
Dose-escalation Cohorts: Time to Reach Maximum Observed Serum Concentration (Tmax) of Avelumab
Tmax was time to reach maximum observed serum concentration obtained directly from the concentration versus time curve.
Time frame: Within 6 hours before the infusion, at end of 1-hour infusion (Day 1), 0.5, 1, 2, 4, 6,12, 24, 36, 48, 168 hours after end of infusion
Population: PK analysis set included all participants who have received at least 1 dose of study treatment and provided at least 1 measurable post-dose concentration.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Dose-escalation Cohort: Avelumab 3 mg/kg | Dose-escalation Cohorts: Time to Reach Maximum Observed Serum Concentration (Tmax) of Avelumab | 1.683 hour |
| Dose-escalation Cohort: Avelumab 10 mg/kg | Dose-escalation Cohorts: Time to Reach Maximum Observed Serum Concentration (Tmax) of Avelumab | 1.533 hour |
| Dose-escalation Cohort: Avelumab 20 mg/kg | Dose-escalation Cohorts: Time to Reach Maximum Observed Serum Concentration (Tmax) of Avelumab | 1.683 hour |
Secondary
Expansion Cohort: Absolute Values of Cytokine Levels
Cytokine analysis was performed to evaluate levels of Monocyte chemoattractant protein-1 (MCP-1) and various interleukins (including IL-5, IL-6, IL-8), Tumor necrosis factors-alpha (TNF-alpha) and Interferon-gamma (IFN-gamma) in serum samples.
Time frame: Day 1 (Pre-infusion), Day 8 (168 hour after infusion) and Day 43 (Pre-infusion)
Population: Safety analysis set included all participants who have received at least 1 dose of study treatment. Here Number Analyzed = participants who were evaluable for this outcome measure at the specified time points for the given category.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Dose-escalation Cohort: Avelumab 3 mg/kg | Expansion Cohort: Absolute Values of Cytokine Levels | IFN-gamma: Day 43: Pre-Infusion | 19.215 nanogram per liter (ng/L) | Standard Deviation 22.041 |
| Dose-escalation Cohort: Avelumab 3 mg/kg | Expansion Cohort: Absolute Values of Cytokine Levels | IL-5: Day 1: Pre-Infusion | 1.139 nanogram per liter (ng/L) | Standard Deviation 1.596 |
| Dose-escalation Cohort: Avelumab 3 mg/kg | Expansion Cohort: Absolute Values of Cytokine Levels | IL-5: Day 8: 168 hours Post Infusion | 1.492 nanogram per liter (ng/L) | Standard Deviation 2.135 |
| Dose-escalation Cohort: Avelumab 3 mg/kg | Expansion Cohort: Absolute Values of Cytokine Levels | IL-5: Day 43: Pre-Infusion | 1.632 nanogram per liter (ng/L) | Standard Deviation 1.958 |
| Dose-escalation Cohort: Avelumab 3 mg/kg | Expansion Cohort: Absolute Values of Cytokine Levels | IL-6: Day 8: 168 hours Post Infusion | 4.102 nanogram per liter (ng/L) | Standard Deviation 8.479 |
| Dose-escalation Cohort: Avelumab 3 mg/kg | Expansion Cohort: Absolute Values of Cytokine Levels | IL-6: Day 43: Pre-Infusion | 1.501 nanogram per liter (ng/L) | Standard Deviation 1.555 |
| Dose-escalation Cohort: Avelumab 3 mg/kg | Expansion Cohort: Absolute Values of Cytokine Levels | MCP-1: Day 1: Pre-Infusion | 671.025 nanogram per liter (ng/L) | Standard Deviation 203.263 |
| Dose-escalation Cohort: Avelumab 3 mg/kg | Expansion Cohort: Absolute Values of Cytokine Levels | MCP-1: Day 8: 168 hours Post Infusion | 730.466 nanogram per liter (ng/L) | Standard Deviation 284.028 |
| Dose-escalation Cohort: Avelumab 3 mg/kg | Expansion Cohort: Absolute Values of Cytokine Levels | MCP-1: Day 43: Pre-Infusion | 775.411 nanogram per liter (ng/L) | Standard Deviation 280.839 |
| Dose-escalation Cohort: Avelumab 3 mg/kg | Expansion Cohort: Absolute Values of Cytokine Levels | TNF-alpha: Day 1: Pre-Infusion | 3.674 nanogram per liter (ng/L) | Standard Deviation 2.081 |
| Dose-escalation Cohort: Avelumab 3 mg/kg | Expansion Cohort: Absolute Values of Cytokine Levels | TNF-alpha: Day 8: 168 hours Post Infusion | 4.475 nanogram per liter (ng/L) | Standard Deviation 4.195 |
| Dose-escalation Cohort: Avelumab 3 mg/kg | Expansion Cohort: Absolute Values of Cytokine Levels | IL-8: Day 1: Pre-Infusion | 46.254 nanogram per liter (ng/L) | Standard Deviation 43.728 |
| Dose-escalation Cohort: Avelumab 3 mg/kg | Expansion Cohort: Absolute Values of Cytokine Levels | IL-8: Day 8: 168 hours Post Infusion | 54.107 nanogram per liter (ng/L) | Standard Deviation 56.734 |
| Dose-escalation Cohort: Avelumab 3 mg/kg | Expansion Cohort: Absolute Values of Cytokine Levels | IFN-gamma: Day 1: Pre-Infusion | 28.125 nanogram per liter (ng/L) | Standard Deviation 97.504 |
| Dose-escalation Cohort: Avelumab 3 mg/kg | Expansion Cohort: Absolute Values of Cytokine Levels | IFN-gamma: Day 8: 168 hours post Infusion | 23.063 nanogram per liter (ng/L) | Standard Deviation 25.899 |
| Dose-escalation Cohort: Avelumab 3 mg/kg | Expansion Cohort: Absolute Values of Cytokine Levels | IL-6: Day 1: Pre-Infusion | 3.502 nanogram per liter (ng/L) | Standard Deviation 7.968 |
| Dose-escalation Cohort: Avelumab 3 mg/kg | Expansion Cohort: Absolute Values of Cytokine Levels | TNF-alpha: Day 43: Pre-Infusion | 3.694 nanogram per liter (ng/L) | Standard Deviation 1.195 |
| Dose-escalation Cohort: Avelumab 3 mg/kg | Expansion Cohort: Absolute Values of Cytokine Levels | IL-8: Day 43: Pre-Infusion | 38.674 nanogram per liter (ng/L) | Standard Deviation 30.178 |
Secondary
Expansion Cohort: Area Under the Serum Concentration-Time Curve From the Time of Dosing to the End of Dose Interval (AUC0-336hour [hr]) of Avelumab
AUC0-336hour was defined as area under the serum concentration-time curve from the time of dosing to the end of dose interval (336 hr). It was calculated by linear trapezoidal summation.
Time frame: Within 6 hours before and the end of the 1-hour infusion (Day 1) and 336 hours after end of infusion
Population: PK analysis set included all participants who have received at least 1 dose of study treatment and provided at least 1 measurable post-dose concentration. Here Number of participants analyzed signifies those participants who were evaluable for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Dose-escalation Cohort: Avelumab 3 mg/kg | Expansion Cohort: Area Under the Serum Concentration-Time Curve From the Time of Dosing to the End of Dose Interval (AUC0-336hour [hr]) of Avelumab | 14.525 mcg/mL | Standard Deviation 6.3064 |
Secondary
Expansion Cohort: Immune-related Progression-Free Survival (irPFS) Time According to Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1
irPFS was defined as the time from the first dose of study treatment to the date of first documentation of immune-related progressive disease \[irPD\] (which was subsequently confirmed) or death due to any cause, whichever occurred first. irPD was defined as the sum of the longest diameters of target and new measurable lesions increases greater than or equal to \[\>=\] 20 percent (%), confirmed by a repeat, consecutive observations at least 4 weeks from the date first documented.
Time frame: Time from first dose of study treatment up to 1906 days
Population: Safety analysis set included all participants who have received at least 1 dose of study treatment.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Dose-escalation Cohort: Avelumab 3 mg/kg | Expansion Cohort: Immune-related Progression-Free Survival (irPFS) Time According to Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 | 12.00 weeks |
Secondary
Expansion Cohort: Log Fold Change From Baseline in Cytokine Levels
Cytokine analysis was performed to evaluate levels of Monocyte chemoattractant protein-1 (MCP-1) and various interleukins (including IL-5, IL-6, IL-8), Tumor necrosis factors-alpha (TNF-alpha) and Interferon-gamma (IFN-gamma) in serum samples. Log fold change from baseline (logFC) was defined as logFC (cytokine at time t) = log (cytokine signal at time t) - log (cytokine signal at baseline).
Time frame: Baseline (Day 1 [Pre-infusion]), Day 8 (168 hour after infusion) and Day 43 (Pre-infusion)
Population: Safety analysis set included all participants who have received at least 1 dose of study treatment. Here Number analyzed = participants who were evaluable for this outcome measure at the specified time points for the given category.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Dose-escalation Cohort: Avelumab 3 mg/kg | Expansion Cohort: Log Fold Change From Baseline in Cytokine Levels | MCP-1: Day 43: Pre-Infusion | 0.115 log fold change | Standard Deviation 0.42 |
| Dose-escalation Cohort: Avelumab 3 mg/kg | Expansion Cohort: Log Fold Change From Baseline in Cytokine Levels | TNF-alpha: Day 8: 168 hours Post Infusion | 0.209 log fold change | Standard Deviation 0.377 |
| Dose-escalation Cohort: Avelumab 3 mg/kg | Expansion Cohort: Log Fold Change From Baseline in Cytokine Levels | TNF-alpha: Day 43: Pre-Infusion | 0.156 log fold change | Standard Deviation 0.366 |
| Dose-escalation Cohort: Avelumab 3 mg/kg | Expansion Cohort: Log Fold Change From Baseline in Cytokine Levels | IL-8: Day 8: 168 hours Post Infusion | 0.199 log fold change | Standard Deviation 0.444 |
| Dose-escalation Cohort: Avelumab 3 mg/kg | Expansion Cohort: Log Fold Change From Baseline in Cytokine Levels | IL-8: Day 43: Pre-Infusion | 0.256 log fold change | Standard Deviation 0.664 |
| Dose-escalation Cohort: Avelumab 3 mg/kg | Expansion Cohort: Log Fold Change From Baseline in Cytokine Levels | IFN-gamma: Day 8: 168 hours Post Infusion | 0.697 log fold change | Standard Deviation 1.14 |
| Dose-escalation Cohort: Avelumab 3 mg/kg | Expansion Cohort: Log Fold Change From Baseline in Cytokine Levels | IFN-gamma: Day 43: Pre-Infusion | 0.484 log fold change | Standard Deviation 1.371 |
| Dose-escalation Cohort: Avelumab 3 mg/kg | Expansion Cohort: Log Fold Change From Baseline in Cytokine Levels | IL-5: Day 8: 168 hours Post Infusion | 0.080 log fold change | Standard Deviation 1.209 |
| Dose-escalation Cohort: Avelumab 3 mg/kg | Expansion Cohort: Log Fold Change From Baseline in Cytokine Levels | IL-5: Day 43: Pre-Infusion | 0.192 log fold change | Standard Deviation 1.466 |
| Dose-escalation Cohort: Avelumab 3 mg/kg | Expansion Cohort: Log Fold Change From Baseline in Cytokine Levels | IL-6: Day 8: 168 hours Post Infusion | 0.476 log fold change | Standard Deviation 2.172 |
| Dose-escalation Cohort: Avelumab 3 mg/kg | Expansion Cohort: Log Fold Change From Baseline in Cytokine Levels | IL-6: Day 43: Pre-Infusion | 0.880 log fold change | Standard Deviation 2.184 |
| Dose-escalation Cohort: Avelumab 3 mg/kg | Expansion Cohort: Log Fold Change From Baseline in Cytokine Levels | MCP-1: Day 8: 168 hours Post Infusion | 0.082 log fold change | Standard Deviation 0.353 |
Secondary
Expansion Cohort: Number of Participants With Best Overall Response (BOR) According to Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1
Confirmed BOR was defined as the best response of any of the complete response (CR), partial response (PR), stable disease (SD) and progressive disease (PD) recorded from the date of randomization until disease progression or recurrence (taking the smallest measurement recorded since the start of treatment as reference). CR: Disappearance of all evidence of target and non-target lesions. PR: At least 30% 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 was defined as at least a 20% increase in the 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. Number of participants with best overall response in each category (CR, PR, SD, PD) was reported.
Time frame: Time from first dose of study treatment up to 1906 days
Population: Safety analysis set included all participants who have received at least 1 dose of study treatment.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Dose-escalation Cohort: Avelumab 3 mg/kg | Expansion Cohort: Number of Participants With Best Overall Response (BOR) According to Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 | Complete response (CR) | 1 Participants |
| Dose-escalation Cohort: Avelumab 3 mg/kg | Expansion Cohort: Number of Participants With Best Overall Response (BOR) According to Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 | Partial Response (PR) | 3 Participants |
| Dose-escalation Cohort: Avelumab 3 mg/kg | Expansion Cohort: Number of Participants With Best Overall Response (BOR) According to Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 | Stable disease (SD) | 17 Participants |
| Dose-escalation Cohort: Avelumab 3 mg/kg | Expansion Cohort: Number of Participants With Best Overall Response (BOR) According to Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 | Progressive disease (PD) | 17 Participants |
| Dose-escalation Cohort: Avelumab 3 mg/kg | Expansion Cohort: Number of Participants With Best Overall Response (BOR) According to Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 | Non-evaluable (NE) | 2 Participants |
Secondary
Expansion Cohort: Number of Participants With Immune-related Best Overall Response (irBOR) According to Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1
BOR: 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 the date of randomization until disease progression or recurrence (taking the smallest measurement recorded since the start of treatment as reference). 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.
Time frame: Time from first dose of study treatment up to 1906 days
Population: Safety analysis set included all participants who have received at least 1 dose of study treatment.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Dose-escalation Cohort: Avelumab 3 mg/kg | Expansion Cohort: Number of Participants With Immune-related Best Overall Response (irBOR) According to Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 | Immune-related Complete response (irCR) | 1 Participants |
| Dose-escalation Cohort: Avelumab 3 mg/kg | Expansion Cohort: Number of Participants With Immune-related Best Overall Response (irBOR) According to Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 | Immune-related Partial Response (irPR) | 3 Participants |
| Dose-escalation Cohort: Avelumab 3 mg/kg | Expansion Cohort: Number of Participants With Immune-related Best Overall Response (irBOR) According to Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 | Immune-related Stable disease (irSD) | 21 Participants |
| Dose-escalation Cohort: Avelumab 3 mg/kg | Expansion Cohort: Number of Participants With Immune-related Best Overall Response (irBOR) According to Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 | Immune-related Progressive disease (irPD) | 9 Participants |
| Dose-escalation Cohort: Avelumab 3 mg/kg | Expansion Cohort: Number of Participants With Immune-related Best Overall Response (irBOR) According to Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 | Non-evaluable (NE) | 6 Participants |
Secondary
Expansion Cohort: Number of Participants With Programmed Death Ligand 1 (PD-L1) Tumor Expression
The PD-L1 expression was evaluated using an established antiPD-L1 immunohistochemistry (IHC) assay.
Time frame: Time from first dose of study treatment up to 1906 days
Population: Safety analysis set included all participants who have received at least 1 dose of study treatment.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Dose-escalation Cohort: Avelumab 3 mg/kg | Expansion Cohort: Number of Participants With Programmed Death Ligand 1 (PD-L1) Tumor Expression | 11 Participants |
Secondary
Expansion Cohort: Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs, TEAEs Leading to Death, and TEAEs Leading to Discontinuation
An Adverse Event (AE) was defined as any unfavourable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of study drug, whether or not considered related to the study drug or worsening of pre-existing medical condition, whether or not related to study drug. A serious adverse event (SAE) was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect or was otherwise considered medically important. TEAEs were those events with onset dates occurring during the on-treatment period for the first time, or if the worsening of an event was during the on-treatment period. TEAEs included both serious TEAEs and non-serious TEAEs.
Time frame: Time from first dose of study treatment up to 1906 days
Population: Safety analysis set included all participants who have received at least one dose of study treatment.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Dose-escalation Cohort: Avelumab 3 mg/kg | Expansion Cohort: Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs, TEAEs Leading to Death, and TEAEs Leading to Discontinuation | TEAEs | 40 Participants |
| Dose-escalation Cohort: Avelumab 3 mg/kg | Expansion Cohort: Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs, TEAEs Leading to Death, and TEAEs Leading to Discontinuation | Serious TEAEs | 11 Participants |
| Dose-escalation Cohort: Avelumab 3 mg/kg | Expansion Cohort: Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs, TEAEs Leading to Death, and TEAEs Leading to Discontinuation | TEAEs Leading to Discontinuation | 7 Participants |
| Dose-escalation Cohort: Avelumab 3 mg/kg | Expansion Cohort: Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs, TEAEs Leading to Death, and TEAEs Leading to Discontinuation | TEAEs Leading To Death | 3 Participants |
Secondary
Expansion Cohort: Number of Participants With Treatment-Emergent Positive Human Anti-Human Antibody (HAHA)
Number of participants with positive HAHA were reported. Participants not having positive HAHA prior to treatment with avelumab and with at least one positive post-baseline result in the HAHA assay were characterized as treatment-emergent. Treatment-emergent participants were further classified as Transient Positive or Persistent positive participants were considered as transient positive if time between first and last positive result was less than 16 weeks apart and a negative result at the most recent visit. Participants were considered as persistent positive if time between first and last positive result \>=16 weeks apart or a positive evaluation at the most recent visit.
Time frame: Day 15 up to Day 1906
Population: Safety analysis set included all participants who have received at least 1 dose of study treatment. Here, Overall Number of Participants Analyzed signified participants who were evaluable for this outcome measure.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Dose-escalation Cohort: Avelumab 3 mg/kg | Expansion Cohort: Number of Participants With Treatment-Emergent Positive Human Anti-Human Antibody (HAHA) | Transient positive treatment emergent | 2 Participants |
| Dose-escalation Cohort: Avelumab 3 mg/kg | Expansion Cohort: Number of Participants With Treatment-Emergent Positive Human Anti-Human Antibody (HAHA) | Persistent positive treatment emergent | 5 Participants |
Secondary
Expansion Cohort: Overall Survival (OS) Time
The OS time was defined as the time from randomization to the date of death. The participants who were still alive at the time of data analysis or who were lost to follow-up OS time was censored at the last recorded date that the participant was known to be alive before the data cutoff date. OS was measured using Kaplan-Meier (KM) estimates.
Time frame: Time from first dose of study treatment up to 1906 days
Population: Safety analysis set included all participants who have received at least 1 dose of study treatment.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Dose-escalation Cohort: Avelumab 3 mg/kg | Expansion Cohort: Overall Survival (OS) Time | 8.87 months |
Secondary
Expansion Cohort: Progression-Free Survival (PFS) Time According to Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1
PFS was defined as the time from date of randomization until date of the first documentation of progressive disease (PD) or death due to any cause in the absence of documented PD, whichever occurs first. PD was defined as at least a 20 percent (%) 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. PFS was measured using Kaplan-Meier (KM) estimates.
Time frame: Time from first dose of study treatment up to 1906 days
Population: Safety analysis set included all participants who have received at least 1 dose of study treatment.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Dose-escalation Cohort: Avelumab 3 mg/kg | Expansion Cohort: Progression-Free Survival (PFS) Time According to Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 | 10.64 weeks |
Secondary
Expansion Cohort: Serum Trough Concentration Levels (Ctrough) of Avelumab
Ctrough was defined as the trough or minimum serum concentration.
Time frame: Within 6 hours before the 1-hour infusion on Day 15, Day 29, Day 43, Day 85, Day 127 and Day 169.
Population: PK analysis set: all participants who have received at least 1 dose of study treatment and provided at least 1 measurable post-dose concentration. Overall Number of Participants Analyzed = participants evaluable for this outcome measure and Number analyzed = participants who were evaluable at the specified time points for the given category.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Dose-escalation Cohort: Avelumab 3 mg/kg | Expansion Cohort: Serum Trough Concentration Levels (Ctrough) of Avelumab | Day 15 | 14.525 mcg/mL | Standard Deviation 6.3064 |
| Dose-escalation Cohort: Avelumab 3 mg/kg | Expansion Cohort: Serum Trough Concentration Levels (Ctrough) of Avelumab | Day 29 | 17.366 mcg/mL | Standard Deviation 9.2981 |
| Dose-escalation Cohort: Avelumab 3 mg/kg | Expansion Cohort: Serum Trough Concentration Levels (Ctrough) of Avelumab | Day 43 | 19.686 mcg/mL | Standard Deviation 9.0747 |
| Dose-escalation Cohort: Avelumab 3 mg/kg | Expansion Cohort: Serum Trough Concentration Levels (Ctrough) of Avelumab | Day 85 | 25.125 mcg/mL | Standard Deviation 14.4089 |
| Dose-escalation Cohort: Avelumab 3 mg/kg | Expansion Cohort: Serum Trough Concentration Levels (Ctrough) of Avelumab | Day 127 | 22.544 mcg/mL | Standard Deviation 16.7706 |
| Dose-escalation Cohort: Avelumab 3 mg/kg | Expansion Cohort: Serum Trough Concentration Levels (Ctrough) of Avelumab | Day 169 | 20.857 mcg/mL | Standard Deviation 23.282 |