Lymphoma, Refractory or Relapsed Solid Tumors
Conditions
Keywords
Avelumab, Anti PD-L1, Solid tumors, CNS tumors, Lymphoma, Pediatric subjects
Brief summary
This is a multi-center, open-label, international study to evaluate the dose, safety and tolerability, antitumor activity, pharmacokinetic and pharmacodynamics of avelumab in pediatric subjects 0 to less than 18 years of age with refractory or relapsed malignant solid tumors (including central nervous system tumors) and lymphoma for which no standard therapy is available or for which the subject is not eligible for the existing therapy. The study was planned to be conducted in 2 parts: the dose-finding part (Phase I) and the tumor-specified expansion part (Phase II). However, Phase II was cancelled due to limited clinical benefit of PD-L1 monotherapy in pediatric participants.
Interventions
DRUGAvelumab
Participants received an intravenous infusion of avelumab 10mg/kg intervention (IV) once every 2 weeks until confirmed progression, death, unacceptable toxicity, or any criterion for withdrawal occurred.
Sponsors
Merck KGaA, Darmstadt, Germany
EMD Serono Research & Development Institute, Inc.
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
0 Years to 18 Years
Healthy volunteers
No
Inclusion criteria
* Male or female subjects 0 to less than 18 years of age at the time of first treatment dose with histologically or cytologically confirmed solid malignant tumors (including CNS tumors) or lymphoma for which no standard therapy is available * Confirmed progression on or refractory to standard therapy or no standard therapy available. * Availability of archival formalin-fixed, paraffin-embedded block containing tumor tissue, or slides, or a fresh/recent tumor biopsy prior to avelumab treatment for subjects in Phase 2 * Adequate bone marrow, kidney, and liver function * Other protocol defined inclusion criteria could apply
Exclusion criteria
* Prior therapy with any antibody or drug targeting T-cell coregulatory proteins * Concurrent anticancer treatment or immunosuppressive agents * Prior organ transplantation * Significant acute or chronic infections * Other significant diseases or conditions that might impair the subject's tolerance of trial treatment * Other protocol defined
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Treatment-Emergent Adverse Events (TEAEs) as Per Severity With Grade 3 or Higher According to National Cancer Institute-Common Terminology Criteria for Adverse Events Version 4.03 (NCI-CTCAE v4.03) | Baseline up to 1182 days | Adverse event (AE) was defined as any untoward medical occurrence in a participant, which does not necessarily have causal relationship with treatment. A serious AE was defined as an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged in participant 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. Severity of grade 3 or higher TEAEs were graded using NCI-CTCAE v4.03 toxicity grades, as follows: Grade 1 = Mild, Grade 2= Moderate, Grade 3 = Severe; Grade 4 = Life-threatening and Grade 5 = Death. Number of participants with TEAEs as per severity with Grade 3 and higher were reported. |
| Number of Participants Who Experienced Dose-Limiting Toxicities (DLTs) | Baseline up to 28 days | For the purpose of dose finding, any of the following AEs occurring during the primary DLT observation period. Hematologic: Grade 4 neutropenia for more than 7 days in duration; Grade greater than or equal to (\>=) 3 neutropenic infection; Grade \>= 3 thrombocytopenia with bleeding; Grade 4 thrombocytopenia \> 7 days and Grade 4 anemia. Nonhematologic: Any Grade \>= 3 toxicity, except for any of the following: Transient (less than or equal to (\<=) 72 hours; Grade 3 flu-like symptoms or fever, which was controlled with medical management; Transient (\<= 72 hours) Grade 3 fatigue, local reactions, headache, nausea, or emesis that resolved to Grade \<= 1 or to Baseline. Grade 3 diarrhea or Grade 3 skin toxicity that resolved to Grade \<= 1 in less than 7 days after medical management (immunosuppressant treatment) had been initiated. Grade \>= 3 amylase or lipase abnormality that was not associated with clinical manifestations of pancreatitis. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Time to Response According to Response Evaluation Criteria in Solid Tumors (RECIST Version 1.1) and as Adjudicated by the Investigator | Time from start of study treatment up to 1182 days | Time to response (TTR) was defined, for participants with an objective response, as the time from the start date of study treatment to the first documentation of OR (CR or PR) which was subsequently confirmed. |
| Progression-Free Survival According to Response Evaluation Criteria in Solid Tumors (RECIST Version 1.1) and as Adjudicated by the Investigator | Time from first administration of study drug until the first documentation of PD or death, assessed up to 1182 days | Progression-Free survival was defined as the time from first administration of study treatment until the first documentation of disease progression (PD) or death due to any cause, whichever occurred first. PD: 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. PFS was measured using Kaplan-Meier (KM) estimates. |
| Overall Survival (OS) | Time from first administration of study drug up to 1182 days | Overall Survival was defined as the time from date of first dose of study drug to the date of death due to any cause. For participants who were still alive at the time of data analysis or who were lost to follow-up, OS time was censored at the date of last contact. OS was measured using Kaplan-Meier (KM) estimates. |
| Number of Participants With Treatment-Emergent Adverse Events, Adverse Events of Special Interest (AESI) and Treatment-related Adverse Events According to NCI-CTCAE v4.03 | Baseline up to 1182 days | Adverse Event (AE) was defined any untoward medical occurrence in a participant administered with a study drug, which does not necessarily had a causal relationship with this treatment. Serious AE was defined AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial/prolonged inpatient hospitalization; congenital anomaly/birth defect. TEAEs: TEAEs was defined as events with onset date or worsening during the on-treatment period. TEAEs included serious AEs and non-serious AEs. Treatment-related TEAEs: reasonably related to the study intervention. AESIs included Infusion-related reactions (IRRs) and Immune-related AE (irAEs). |
| Number of Participants With Grade 3 or Higher Laboratory Abnormalities According to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) Version 4.03 | Baseline up to 1182 days | The total number of participants with laboratory test abnormalities were assessed. Clinical laboratory tests included hematology and biochemistry abnormalities. The hematology and biochemistry abnormalities (by worst on-treatment NCI-CTCAE Grade 3 and Grade 4) were reported. Laboratory abnormalities were graded using NCI-CTCAE v4.03 toxicity grades, as follows: Grade 1 = Mild, Grade 2= Moderate, Grade 3 = Severe; Grade 4 = Life-threatening and Grade 5 = Death. |
| Maximum Observed Serum Concentration (Cmax) of Avelumab | Pre-dose, end of infusion (1 hour), 3 hours post-dose on Day 1, cycle 1 (each cycle is for 14 days) | Cmax is the maximum observed serum concentration obtained directly from the concentration versus time curve. |
| Area Under the Serum Concentration-Time Curve From Time Zero to the 336 Hours Post-Dose (AUC 0-336 Hours) of Avelumab | Pre-dose, end of infusion (1 hour), 3 hours to 336 hours post-dose | Area under the serum concentration-time curve from time zero to the 336 Hours Post-Dose (AUC 0-336 hours) of Avelumab were calculated. Calculated using the mixed loglinear trapezoidal rule (linear up, log down). |
| Apparent Terminal Half Life (t1/2) of Avelumab | Pre-dose, end of infusion (1 hour), 3 hours post-dose on Day 1, cycle 1 (each cycle is for 14 days) | Apparent terminal half-life was defined as the time required for the plasma concentration of drug to decrease 50 percent in the final stage of its elimination. Apparent terminal half-life. t1/2 = log (ln) 2/lambdaz (λz). |
| Number of Participants With Confirmed Best Overall Response (BOR) as Per Response Evaluation Criteria in Solid Tumors (RECIST Version 1.1) and as Adjudicated by the Investigator | Baseline up to 1182 days | Confirmed BOR was evaluated based on RECIST v1.1 and Investigator's assessments and defined as best response of any of confirmed complete response (CR), partial response (PR), stable disease (SD) and progressive disease (PD) recorded from date of study treatment until disease progression. CR: Disappearance of all evidence of target/non-target lesions. PR: At least 30 percent (%) reduction from baseline in sum of longest diameter (SLD) of all lesions. SD: Neither sufficient increase to qualify for PD nor sufficient shrinkage to qualify for PR. PD: at least a 20% increase in SLD, taking as reference smallest SLD recorded from baseline/appearance of 1or more new lesions and unequivocal progression of non-target lesions. |
| Number of Participants With Positive Treatment Emergent Anti-drug Antibodies (ADA) and Neutralizing Antibodies (Nabs) | Baseline up to 1182 days | Serum samples were analyzed by a validated electrochemiluminesce immunoassay to detect the presence of anti-drug antibodies and neutralizing antibodies. Samples that screened positive were subsequently tested in a confirmatory assay. Those confirmed positive were tittered for a quasi-quantitative result. Number of participants with positive treatment emergent anti-drug antibodies and neutralizing antibodies were reported. Participants not positive prior to treatment with avelumab and with at least one positive result in the human-Antihuman Antibodies assay were characterized as treatment-emergent. |
| Number of Participants With Positive Tumor Programmed Death Ligand 1 (PD-L1) Expression | Baseline up to end of treatment visit (27.5 weeks) | Number of participants with positive tumor programmed death ligand 1 (PDL-1) with cut off \>=1%, \>= 5%, \>=25%, \>=50% and \>=80% expression were reported. |
| Number of Participants With Substantial, Sustained, or Significant Changes From Baseline for Tumor-Infiltrating T-cell Levels | Baseline up to end of treatment visit (27.5 weeks) | Number of participants with substantial, sustained, or significant changes from baseline for Tumor-Infiltrating T-cell Levels were reported. Significant clinical deterioration (clinical progression), defined as new symptoms that are deemed by the Investigator to be clinically significant or significant worsening of existing symptoms. |
| Number of Participants With Substantial, Sustained, or Significant Changes From Baseline for T-cell Population in Blood | Baseline up to end of treatment visit (27.5 weeks) | Number of participants with substantial, sustained, or significant changes from baseline for T-cell population in blood were reported. Significant clinical deterioration (clinical progression), defined as new symptoms that are deemed by the Investigator to be clinically significant or significant worsening of existing symptoms. |
| Number of Participants With Substantial, Sustained, or Significant Changes From Baseline for B-cell and Natural Killer Cell (NK-Cell) in Blood | Baseline up to end of treatment visit (27.5 weeks) | Number of participants with substantial, sustained, or significant changes from baseline for B-cell and NK-cell in blood were reported. Significant clinical deterioration (clinical progression), defined as new symptoms that are deemed by the Investigator to be clinically significant or significant worsening of existing symptoms. |
| Number of Participants With Substantial, Sustained, or Significant Changes From Baseline for Vaccination-Related Antibody Concentrations | Baseline up to end of treatment visit (27.5 weeks) | Samples for the testing of vaccination-related antibody concentrations for diphtheria, tetanus, and pneumococcal conjugate (PCV-7) were collected. Significant clinical deterioration (clinical progression), defined as new symptoms that are deemed by the Investigator to be clinically significant or significant worsening of existing symptoms. |
| Number of Participants With TEAEs Related to Vital Signs That Resulted in Treatment Discontinuation | Baseline up to 1182 days | Vital signs included: Body temperature, Heart Rate, Blood pressure and respiratory rate. Vital signs were measured in semi-supine position after 5 minutes rest for the participants. |
| Minimum Serum Post-dose Trough (Ctrough) Concentration of Avelumab | Pre-dose at Day 15 | The concentration observed immediately before next dosing (corresponding to predose or trough concentration for multiple dosing) was calculated. |
| Duration of Response (DOR) as Per Response Evaluation Criteria in Solid Tumors (RECIST Version 1.1) and as Adjudicated by the Investigator | Time from first documentation of objective response up to 1182 days | Duration of response was defined for participants with confirmed objective response (OR), as the time from first documentation of objective response (Complete Response or Partial Response) to the date of first documentation of objective PD or death due to any cause, whichever occurred first. CR: Disappearance of all evidence of target and non-target lesions. PR: At least 30% reduction from baseline in the SLD of all lesions. PD: 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. DOR was determined according to RECIST v1.1 and assessed by Investigator. |
Countries
Belgium, Canada, Denmark, South Korea, United States
Participant flow
Recruitment details
A total of 26 participants were screened for participation in the Phase I part of the study, out of which 21 participants were eligible and received the study treatment.
Pre-assignment details
The study was planned to be conducted in 2 parts: the dose-finding part (Phase I) and the tumor-specified expansion part (Phase II). However, Phase II was cancelled due to limited clinical benefit of Programmed death ligand 1 (PD-L1) monotherapy in pediatric participants.
Participants by arm
| Arm | Count |
|---|---|
| Avelumab 10 Miligram Per Kilogram (mg/kg) Participants received an intravenous infusion of avelumab 10mg/kg intervention (IV) once every 2 weeks until confirmed progression, death, unacceptable toxicity, or any criterion for withdrawal occurred. | 6 |
| Avelumab 20 mg/kg Participants received an intravenous infusion of avelumab 20 mg/kg IV once every 2 weeks until confirmed progression, death, unacceptable toxicity, or any criterion for withdrawal occurred. | 15 |
| Total | 21 |
Baseline characteristics
| Characteristic | Avelumab 20 mg/kg | Total | Avelumab 10 Miligram Per Kilogram (mg/kg) |
|---|---|---|---|
| Age, Continuous | 10.7 Years STANDARD_DEVIATION 5.02 | 11.1 Years STANDARD_DEVIATION 4.52 | 12.0 Years STANDARD_DEVIATION 3.1 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 13 Participants | 19 Participants | 6 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 2 Participants | 2 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 9 Participants | 15 Participants | 6 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 2 Participants | 2 Participants | 0 Participants |
| Race (NIH/OMB) White | 4 Participants | 4 Participants | 0 Participants |
| Sex: Female, Male Female | 8 Participants | 10 Participants | 2 Participants |
| Sex: Female, Male Male | 7 Participants | 11 Participants | 4 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 6 / 6 | 12 / 15 |
| other Total, other adverse events | 0 / 0 | 0 / 0 |
| serious Total, serious adverse events | 6 / 6 | 15 / 15 |
Outcome results
Primary
Number of Participants Who Experienced Dose-Limiting Toxicities (DLTs)
For the purpose of dose finding, any of the following AEs occurring during the primary DLT observation period. Hematologic: Grade 4 neutropenia for more than 7 days in duration; Grade greater than or equal to (\>=) 3 neutropenic infection; Grade \>= 3 thrombocytopenia with bleeding; Grade 4 thrombocytopenia \> 7 days and Grade 4 anemia. Nonhematologic: Any Grade \>= 3 toxicity, except for any of the following: Transient (less than or equal to (\<=) 72 hours; Grade 3 flu-like symptoms or fever, which was controlled with medical management; Transient (\<= 72 hours) Grade 3 fatigue, local reactions, headache, nausea, or emesis that resolved to Grade \<= 1 or to Baseline. Grade 3 diarrhea or Grade 3 skin toxicity that resolved to Grade \<= 1 in less than 7 days after medical management (immunosuppressant treatment) had been initiated. Grade \>= 3 amylase or lipase abnormality that was not associated with clinical manifestations of pancreatitis.
Time frame: Baseline up to 28 days
Population: The DLT analysis set includes all participants who meet either of the following criteria: Have received 100 percent (% ) of all planned doses of treatment during the DLT evaluation period (first 2 cycles of treatment) and have been followed for at least 28 days or have stopped treatment because of a DLT in the DLT evaluation period.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Avelumab 10 Miligram Per Kilogram (mg/kg) | Number of Participants Who Experienced Dose-Limiting Toxicities (DLTs) | 0 Participants |
| Avelumab 20 mg/kg | Number of Participants Who Experienced Dose-Limiting Toxicities (DLTs) | 1 Participants |
Primary
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) as Per Severity With Grade 3 or Higher According to National Cancer Institute-Common Terminology Criteria for Adverse Events Version 4.03 (NCI-CTCAE v4.03)
Adverse event (AE) was defined as any untoward medical occurrence in a participant, which does not necessarily have causal relationship with treatment. A serious AE was defined as an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged in participant 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. Severity of grade 3 or higher TEAEs were graded using NCI-CTCAE v4.03 toxicity grades, as follows: Grade 1 = Mild, Grade 2= Moderate, Grade 3 = Severe; Grade 4 = Life-threatening and Grade 5 = Death. Number of participants with TEAEs as per severity with Grade 3 and higher were reported.
Time frame: Baseline up to 1182 days
Population: Safety analysis set included all participants who received any dose of avelumab.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Avelumab 10 Miligram Per Kilogram (mg/kg) | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) as Per Severity With Grade 3 or Higher According to National Cancer Institute-Common Terminology Criteria for Adverse Events Version 4.03 (NCI-CTCAE v4.03) | Participants With TEAEs: Grade 3 | 4 Participants |
| Avelumab 10 Miligram Per Kilogram (mg/kg) | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) as Per Severity With Grade 3 or Higher According to National Cancer Institute-Common Terminology Criteria for Adverse Events Version 4.03 (NCI-CTCAE v4.03) | Participants With TEAEs: Grade 4 | 0 Participants |
| Avelumab 10 Miligram Per Kilogram (mg/kg) | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) as Per Severity With Grade 3 or Higher According to National Cancer Institute-Common Terminology Criteria for Adverse Events Version 4.03 (NCI-CTCAE v4.03) | Participants With TEAEs: Grade 5 | 1 Participants |
| Avelumab 20 mg/kg | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) as Per Severity With Grade 3 or Higher According to National Cancer Institute-Common Terminology Criteria for Adverse Events Version 4.03 (NCI-CTCAE v4.03) | Participants With TEAEs: Grade 3 | 6 Participants |
| Avelumab 20 mg/kg | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) as Per Severity With Grade 3 or Higher According to National Cancer Institute-Common Terminology Criteria for Adverse Events Version 4.03 (NCI-CTCAE v4.03) | Participants With TEAEs: Grade 4 | 2 Participants |
| Avelumab 20 mg/kg | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) as Per Severity With Grade 3 or Higher According to National Cancer Institute-Common Terminology Criteria for Adverse Events Version 4.03 (NCI-CTCAE v4.03) | Participants With TEAEs: Grade 5 | 3 Participants |
Secondary
Apparent Terminal Half Life (t1/2) of Avelumab
Apparent terminal half-life was defined as the time required for the plasma concentration of drug to decrease 50 percent in the final stage of its elimination. Apparent terminal half-life. t1/2 = log (ln) 2/lambdaz (λz).
Time frame: Pre-dose, end of infusion (1 hour), 3 hours post-dose on Day 1, cycle 1 (each cycle is for 14 days)
Population: The PK analysis set included all participants who received at least one dose of avelumab, had no important protocol deviations or important events affecting PK, and provided at least one measurable post-dose concentration. Here, Number of participants analyzed are those who are evaluable for this outcome measure.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Avelumab 10 Miligram Per Kilogram (mg/kg) | Apparent Terminal Half Life (t1/2) of Avelumab | 85.9 hours | Geometric Coefficient of Variation 15.1 |
| Avelumab 20 mg/kg | Apparent Terminal Half Life (t1/2) of Avelumab | 119 hours | Geometric Coefficient of Variation 73.7 |
Secondary
Area Under the Serum Concentration-Time Curve From Time Zero to the 336 Hours Post-Dose (AUC 0-336 Hours) of Avelumab
Area under the serum concentration-time curve from time zero to the 336 Hours Post-Dose (AUC 0-336 hours) of Avelumab were calculated. Calculated using the mixed loglinear trapezoidal rule (linear up, log down).
Time frame: Pre-dose, end of infusion (1 hour), 3 hours to 336 hours post-dose
Population: The PK analysis set included all particpants who received at least one dose of avelumab, had no important protocol deviations or important events affecting PK, and provided at least one measurable post-dose concentration. Here number of participants analyzed are those who are evaluable for this outcome measure.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Avelumab 10 Miligram Per Kilogram (mg/kg) | Area Under the Serum Concentration-Time Curve From Time Zero to the 336 Hours Post-Dose (AUC 0-336 Hours) of Avelumab | 18800 microgram*hour per mililiter (mcg•h/mL) | Geometric Coefficient of Variation 29.2 |
| Avelumab 20 mg/kg | Area Under the Serum Concentration-Time Curve From Time Zero to the 336 Hours Post-Dose (AUC 0-336 Hours) of Avelumab | 43500 microgram*hour per mililiter (mcg•h/mL) | Geometric Coefficient of Variation 21.5 |
Secondary
Duration of Response (DOR) as Per Response Evaluation Criteria in Solid Tumors (RECIST Version 1.1) and as Adjudicated by the Investigator
Duration of response was defined for participants with confirmed objective response (OR), as the time from first documentation of objective response (Complete Response or Partial Response) to the date of first documentation of objective PD or death due to any cause, whichever occurred first. CR: Disappearance of all evidence of target and non-target lesions. PR: At least 30% reduction from baseline in the SLD of all lesions. PD: 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. DOR was determined according to RECIST v1.1 and assessed by Investigator.
Time frame: Time from first documentation of objective response up to 1182 days
Population: Data could not be calculated as none of the participants showed objective response.
Secondary
Maximum Observed Serum Concentration (Cmax) of Avelumab
Cmax is the maximum observed serum concentration obtained directly from the concentration versus time curve.
Time frame: Pre-dose, end of infusion (1 hour), 3 hours post-dose on Day 1, cycle 1 (each cycle is for 14 days)
Population: The Pharmacokinetic (PK) analysis set included all participants who received at least one dose of avelumab, had no important protocol deviations or important events affecting PK, and provided at least one measurable post-dose concentration.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Avelumab 10 Miligram Per Kilogram (mg/kg) | Maximum Observed Serum Concentration (Cmax) of Avelumab | 190 microgram per mililiter (mcg/mL) | Geometric Coefficient of Variation 34.5 |
| Avelumab 20 mg/kg | Maximum Observed Serum Concentration (Cmax) of Avelumab | 384 microgram per mililiter (mcg/mL) | Geometric Coefficient of Variation 27.3 |
Secondary
Minimum Serum Post-dose Trough (Ctrough) Concentration of Avelumab
The concentration observed immediately before next dosing (corresponding to predose or trough concentration for multiple dosing) was calculated.
Time frame: Pre-dose at Day 15
Population: The PK analysis set included all participants who received at least one dose of avelumab, had no important protocol deviations or important events affecting PK, and provided at least one measurable post-dose concentration.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Avelumab 10 Miligram Per Kilogram (mg/kg) | Minimum Serum Post-dose Trough (Ctrough) Concentration of Avelumab | 11.2 microgram per ml (mcg/mL) | Geometric Coefficient of Variation 44.9 |
| Avelumab 20 mg/kg | Minimum Serum Post-dose Trough (Ctrough) Concentration of Avelumab | 34.8 microgram per ml (mcg/mL) | Geometric Coefficient of Variation 77.8 |
Secondary
Number of Participants With Confirmed Best Overall Response (BOR) as Per Response Evaluation Criteria in Solid Tumors (RECIST Version 1.1) and as Adjudicated by the Investigator
Confirmed BOR was evaluated based on RECIST v1.1 and Investigator's assessments and defined as best response of any of confirmed complete response (CR), partial response (PR), stable disease (SD) and progressive disease (PD) recorded from date of study treatment until disease progression. CR: Disappearance of all evidence of target/non-target lesions. PR: At least 30 percent (%) reduction from baseline in sum of longest diameter (SLD) of all lesions. SD: Neither sufficient increase to qualify for PD nor sufficient shrinkage to qualify for PR. PD: at least a 20% increase in SLD, taking as reference smallest SLD recorded from baseline/appearance of 1or more new lesions and unequivocal progression of non-target lesions.
Time frame: Baseline up to 1182 days
Population: Full analysis set included all participants who received any dose of avelumab.
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Avelumab 10 Miligram Per Kilogram (mg/kg) | Number of Participants With Confirmed Best Overall Response (BOR) as Per Response Evaluation Criteria in Solid Tumors (RECIST Version 1.1) and as Adjudicated by the Investigator | Complete Response (CR) | 0 Participants |
| Avelumab 10 Miligram Per Kilogram (mg/kg) | Number of Participants With Confirmed Best Overall Response (BOR) as Per Response Evaluation Criteria in Solid Tumors (RECIST Version 1.1) and as Adjudicated by the Investigator | Partial Response (PR) | 0 Participants |
| Avelumab 10 Miligram Per Kilogram (mg/kg) | Number of Participants With Confirmed Best Overall Response (BOR) as Per Response Evaluation Criteria in Solid Tumors (RECIST Version 1.1) and as Adjudicated by the Investigator | Stable Disease (SD) | 0 Participants |
| Avelumab 10 Miligram Per Kilogram (mg/kg) | Number of Participants With Confirmed Best Overall Response (BOR) as Per Response Evaluation Criteria in Solid Tumors (RECIST Version 1.1) and as Adjudicated by the Investigator | Non-CR/Non-PR | 0 Participants |
| Avelumab 10 Miligram Per Kilogram (mg/kg) | Number of Participants With Confirmed Best Overall Response (BOR) as Per Response Evaluation Criteria in Solid Tumors (RECIST Version 1.1) and as Adjudicated by the Investigator | Progressive Disease (PD) | 5 Participants |
| Avelumab 10 Miligram Per Kilogram (mg/kg) | Number of Participants With Confirmed Best Overall Response (BOR) as Per Response Evaluation Criteria in Solid Tumors (RECIST Version 1.1) and as Adjudicated by the Investigator | Not Evaluable | 1 Participants |
| Avelumab 20 mg/kg | Number of Participants With Confirmed Best Overall Response (BOR) as Per Response Evaluation Criteria in Solid Tumors (RECIST Version 1.1) and as Adjudicated by the Investigator | Progressive Disease (PD) | 9 Participants |
| Avelumab 20 mg/kg | Number of Participants With Confirmed Best Overall Response (BOR) as Per Response Evaluation Criteria in Solid Tumors (RECIST Version 1.1) and as Adjudicated by the Investigator | Complete Response (CR) | 0 Participants |
| Avelumab 20 mg/kg | Number of Participants With Confirmed Best Overall Response (BOR) as Per Response Evaluation Criteria in Solid Tumors (RECIST Version 1.1) and as Adjudicated by the Investigator | Non-CR/Non-PR | 0 Participants |
| Avelumab 20 mg/kg | Number of Participants With Confirmed Best Overall Response (BOR) as Per Response Evaluation Criteria in Solid Tumors (RECIST Version 1.1) and as Adjudicated by the Investigator | Partial Response (PR) | 0 Participants |
| Avelumab 20 mg/kg | Number of Participants With Confirmed Best Overall Response (BOR) as Per Response Evaluation Criteria in Solid Tumors (RECIST Version 1.1) and as Adjudicated by the Investigator | Not Evaluable | 2 Participants |
| Avelumab 20 mg/kg | Number of Participants With Confirmed Best Overall Response (BOR) as Per Response Evaluation Criteria in Solid Tumors (RECIST Version 1.1) and as Adjudicated by the Investigator | Stable Disease (SD) | 4 Participants |
Secondary
Number of Participants With Grade 3 or Higher Laboratory Abnormalities According to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) Version 4.03
The total number of participants with laboratory test abnormalities were assessed. Clinical laboratory tests included hematology and biochemistry abnormalities. The hematology and biochemistry abnormalities (by worst on-treatment NCI-CTCAE Grade 3 and Grade 4) were reported. Laboratory abnormalities were graded using NCI-CTCAE v4.03 toxicity grades, as follows: Grade 1 = Mild, Grade 2= Moderate, Grade 3 = Severe; Grade 4 = Life-threatening and Grade 5 = Death.
Time frame: Baseline up to 1182 days
Population: Safety analysis set included all participants who received any dose of avelumab.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Avelumab 10 Miligram Per Kilogram (mg/kg) | Number of Participants With Grade 3 or Higher Laboratory Abnormalities According to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) Version 4.03 | Grade 3: hypokalemia | 0 Participants |
| Avelumab 10 Miligram Per Kilogram (mg/kg) | Number of Participants With Grade 3 or Higher Laboratory Abnormalities According to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) Version 4.03 | Grade 3: lymphocyte count decreased | 1 Participants |
| Avelumab 10 Miligram Per Kilogram (mg/kg) | Number of Participants With Grade 3 or Higher Laboratory Abnormalities According to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) Version 4.03 | Grade 4: platelet count decreased | 0 Participants |
| Avelumab 10 Miligram Per Kilogram (mg/kg) | Number of Participants With Grade 3 or Higher Laboratory Abnormalities According to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) Version 4.03 | Grade 3: hyponatremia | 1 Participants |
| Avelumab 10 Miligram Per Kilogram (mg/kg) | Number of Participants With Grade 3 or Higher Laboratory Abnormalities According to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) Version 4.03 | Grade 3: hyperkalemia | 1 Participants |
| Avelumab 10 Miligram Per Kilogram (mg/kg) | Number of Participants With Grade 3 or Higher Laboratory Abnormalities According to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) Version 4.03 | Grade 3: creatinine increased | 1 Participants |
| Avelumab 10 Miligram Per Kilogram (mg/kg) | Number of Participants With Grade 3 or Higher Laboratory Abnormalities According to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) Version 4.03 | Grade 3: alkaline phosphatase increased | 1 Participants |
| Avelumab 10 Miligram Per Kilogram (mg/kg) | Number of Participants With Grade 3 or Higher Laboratory Abnormalities According to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) Version 4.03 | Grade 3: serum amylase increased | 0 Participants |
| Avelumab 10 Miligram Per Kilogram (mg/kg) | Number of Participants With Grade 3 or Higher Laboratory Abnormalities According to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) Version 4.03 | Grade 4: Hyperkalemia | 0 Participants |
| Avelumab 10 Miligram Per Kilogram (mg/kg) | Number of Participants With Grade 3 or Higher Laboratory Abnormalities According to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) Version 4.03 | Grade 3: Anemia: | 1 Participants |
| Avelumab 20 mg/kg | Number of Participants With Grade 3 or Higher Laboratory Abnormalities According to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) Version 4.03 | Grade 4: Hyperkalemia | 1 Participants |
| Avelumab 20 mg/kg | Number of Participants With Grade 3 or Higher Laboratory Abnormalities According to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) Version 4.03 | Grade 3: Anemia: | 1 Participants |
| Avelumab 20 mg/kg | Number of Participants With Grade 3 or Higher Laboratory Abnormalities According to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) Version 4.03 | Grade 3: creatinine increased | 0 Participants |
| Avelumab 20 mg/kg | Number of Participants With Grade 3 or Higher Laboratory Abnormalities According to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) Version 4.03 | Grade 3: lymphocyte count decreased | 2 Participants |
| Avelumab 20 mg/kg | Number of Participants With Grade 3 or Higher Laboratory Abnormalities According to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) Version 4.03 | Grade 3: serum amylase increased | 1 Participants |
| Avelumab 20 mg/kg | Number of Participants With Grade 3 or Higher Laboratory Abnormalities According to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) Version 4.03 | Grade 4: platelet count decreased | 1 Participants |
| Avelumab 20 mg/kg | Number of Participants With Grade 3 or Higher Laboratory Abnormalities According to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) Version 4.03 | Grade 3: alkaline phosphatase increased | 1 Participants |
| Avelumab 20 mg/kg | Number of Participants With Grade 3 or Higher Laboratory Abnormalities According to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) Version 4.03 | Grade 3: hyponatremia | 3 Participants |
| Avelumab 20 mg/kg | Number of Participants With Grade 3 or Higher Laboratory Abnormalities According to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) Version 4.03 | Grade 3: hypokalemia | 2 Participants |
| Avelumab 20 mg/kg | Number of Participants With Grade 3 or Higher Laboratory Abnormalities According to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) Version 4.03 | Grade 3: hyperkalemia | 0 Participants |
Secondary
Number of Participants With Positive Treatment Emergent Anti-drug Antibodies (ADA) and Neutralizing Antibodies (Nabs)
Serum samples were analyzed by a validated electrochemiluminesce immunoassay to detect the presence of anti-drug antibodies and neutralizing antibodies. Samples that screened positive were subsequently tested in a confirmatory assay. Those confirmed positive were tittered for a quasi-quantitative result. Number of participants with positive treatment emergent anti-drug antibodies and neutralizing antibodies were reported. Participants not positive prior to treatment with avelumab and with at least one positive result in the human-Antihuman Antibodies assay were characterized as treatment-emergent.
Time frame: Baseline up to 1182 days
Population: Immunogenicity Analysis Set included all partiicpants who received any dose of avelumab and have at least one valid ADA result.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Avelumab 10 Miligram Per Kilogram (mg/kg) | Number of Participants With Positive Treatment Emergent Anti-drug Antibodies (ADA) and Neutralizing Antibodies (Nabs) | Participants With Anti-drug Antibodies | 1 Participants |
| Avelumab 10 Miligram Per Kilogram (mg/kg) | Number of Participants With Positive Treatment Emergent Anti-drug Antibodies (ADA) and Neutralizing Antibodies (Nabs) | Participants With Neutralizing Antibodies | 1 Participants |
| Avelumab 20 mg/kg | Number of Participants With Positive Treatment Emergent Anti-drug Antibodies (ADA) and Neutralizing Antibodies (Nabs) | Participants With Anti-drug Antibodies | 0 Participants |
| Avelumab 20 mg/kg | Number of Participants With Positive Treatment Emergent Anti-drug Antibodies (ADA) and Neutralizing Antibodies (Nabs) | Participants With Neutralizing Antibodies | 0 Participants |
Secondary
Number of Participants With Positive Tumor Programmed Death Ligand 1 (PD-L1) Expression
Number of participants with positive tumor programmed death ligand 1 (PDL-1) with cut off \>=1%, \>= 5%, \>=25%, \>=50% and \>=80% expression were reported.
Time frame: Baseline up to end of treatment visit (27.5 weeks)
Population: Biomarker Analysis Set included all participants who received any dose of avelumab and who have provided at least one blood, serum, plasma, or tumor sample for biomarker assessments.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Avelumab 10 Miligram Per Kilogram (mg/kg) | Number of Participants With Positive Tumor Programmed Death Ligand 1 (PD-L1) Expression | PD-L1 expression at cut-off of >=5% | 0 Participants |
| Avelumab 10 Miligram Per Kilogram (mg/kg) | Number of Participants With Positive Tumor Programmed Death Ligand 1 (PD-L1) Expression | PD-L1 expression at cut-off of >=50% | 0 Participants |
| Avelumab 10 Miligram Per Kilogram (mg/kg) | Number of Participants With Positive Tumor Programmed Death Ligand 1 (PD-L1) Expression | PD-L1 expression at cut-off of >=25% | 0 Participants |
| Avelumab 10 Miligram Per Kilogram (mg/kg) | Number of Participants With Positive Tumor Programmed Death Ligand 1 (PD-L1) Expression | PD-L1 expression at cut-off of >=80% | 0 Participants |
| Avelumab 10 Miligram Per Kilogram (mg/kg) | Number of Participants With Positive Tumor Programmed Death Ligand 1 (PD-L1) Expression | PD-L1 expression at cut-off (>=)1% | 0 Participants |
| Avelumab 20 mg/kg | Number of Participants With Positive Tumor Programmed Death Ligand 1 (PD-L1) Expression | PD-L1 expression at cut-off of >=80% | 2 Participants |
| Avelumab 20 mg/kg | Number of Participants With Positive Tumor Programmed Death Ligand 1 (PD-L1) Expression | PD-L1 expression at cut-off (>=)1% | 5 Participants |
| Avelumab 20 mg/kg | Number of Participants With Positive Tumor Programmed Death Ligand 1 (PD-L1) Expression | PD-L1 expression at cut-off of >=5% | 4 Participants |
| Avelumab 20 mg/kg | Number of Participants With Positive Tumor Programmed Death Ligand 1 (PD-L1) Expression | PD-L1 expression at cut-off of >=25% | 3 Participants |
| Avelumab 20 mg/kg | Number of Participants With Positive Tumor Programmed Death Ligand 1 (PD-L1) Expression | PD-L1 expression at cut-off of >=50% | 2 Participants |
Secondary
Number of Participants With Substantial, Sustained, or Significant Changes From Baseline for B-cell and Natural Killer Cell (NK-Cell) in Blood
Number of participants with substantial, sustained, or significant changes from baseline for B-cell and NK-cell in blood were reported. Significant clinical deterioration (clinical progression), defined as new symptoms that are deemed by the Investigator to be clinically significant or significant worsening of existing symptoms.
Time frame: Baseline up to end of treatment visit (27.5 weeks)
Population: Due to early termination of the study, the data for this outcome measure was not collected.
Secondary
Number of Participants With Substantial, Sustained, or Significant Changes From Baseline for T-cell Population in Blood
Number of participants with substantial, sustained, or significant changes from baseline for T-cell population in blood were reported. Significant clinical deterioration (clinical progression), defined as new symptoms that are deemed by the Investigator to be clinically significant or significant worsening of existing symptoms.
Time frame: Baseline up to end of treatment visit (27.5 weeks)
Population: Due to early termination of the study, the data for this outcome measure was not collected.
Secondary
Number of Participants With Substantial, Sustained, or Significant Changes From Baseline for Tumor-Infiltrating T-cell Levels
Number of participants with substantial, sustained, or significant changes from baseline for Tumor-Infiltrating T-cell Levels were reported. Significant clinical deterioration (clinical progression), defined as new symptoms that are deemed by the Investigator to be clinically significant or significant worsening of existing symptoms.
Time frame: Baseline up to end of treatment visit (27.5 weeks)
Population: Since all evaluable tumor tissue samples were collected at baseline and no evaluable sample was provided at end of treatment as planned, an analysis of participants with substantial, sustained, or significant changes from baseline for tumor-infiltrating T-cell levels could not be performed.
Secondary
Number of Participants With Substantial, Sustained, or Significant Changes From Baseline for Vaccination-Related Antibody Concentrations
Samples for the testing of vaccination-related antibody concentrations for diphtheria, tetanus, and pneumococcal conjugate (PCV-7) were collected. Significant clinical deterioration (clinical progression), defined as new symptoms that are deemed by the Investigator to be clinically significant or significant worsening of existing symptoms.
Time frame: Baseline up to end of treatment visit (27.5 weeks)
Population: Due to early termination of the study, the data for this outcome measure was not collected.
Secondary
Number of Participants With TEAEs Related to Vital Signs That Resulted in Treatment Discontinuation
Vital signs included: Body temperature, Heart Rate, Blood pressure and respiratory rate. Vital signs were measured in semi-supine position after 5 minutes rest for the participants.
Time frame: Baseline up to 1182 days
Population: The safety analysis set included all participants who received any dose of avelumab.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Avelumab 10 Miligram Per Kilogram (mg/kg) | Number of Participants With TEAEs Related to Vital Signs That Resulted in Treatment Discontinuation | 0 Participants |
| Avelumab 20 mg/kg | Number of Participants With TEAEs Related to Vital Signs That Resulted in Treatment Discontinuation | 0 Participants |
Secondary
Number of Participants With Treatment-Emergent Adverse Events, Adverse Events of Special Interest (AESI) and Treatment-related Adverse Events According to NCI-CTCAE v4.03
Adverse Event (AE) was defined any untoward medical occurrence in a participant administered with a study drug, which does not necessarily had a causal relationship with this treatment. Serious AE was defined AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial/prolonged inpatient hospitalization; congenital anomaly/birth defect. TEAEs: TEAEs was defined as events with onset date or worsening during the on-treatment period. TEAEs included serious AEs and non-serious AEs. Treatment-related TEAEs: reasonably related to the study intervention. AESIs included Infusion-related reactions (IRRs) and Immune-related AE (irAEs).
Time frame: Baseline up to 1182 days
Population: The safety analysis set included all participants who received any dose of avelumab.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Avelumab 10 Miligram Per Kilogram (mg/kg) | Number of Participants With Treatment-Emergent Adverse Events, Adverse Events of Special Interest (AESI) and Treatment-related Adverse Events According to NCI-CTCAE v4.03 | Participants with any TEAEs | 6 Participants |
| Avelumab 10 Miligram Per Kilogram (mg/kg) | Number of Participants With Treatment-Emergent Adverse Events, Adverse Events of Special Interest (AESI) and Treatment-related Adverse Events According to NCI-CTCAE v4.03 | Participants with Treatment-emergent irAE | 0 Participants |
| Avelumab 10 Miligram Per Kilogram (mg/kg) | Number of Participants With Treatment-Emergent Adverse Events, Adverse Events of Special Interest (AESI) and Treatment-related Adverse Events According to NCI-CTCAE v4.03 | Participants with Treatment-emergent IRR | 2 Participants |
| Avelumab 10 Miligram Per Kilogram (mg/kg) | Number of Participants With Treatment-Emergent Adverse Events, Adverse Events of Special Interest (AESI) and Treatment-related Adverse Events According to NCI-CTCAE v4.03 | Participants with Study-drug related TEAEs | 3 Participants |
| Avelumab 20 mg/kg | Number of Participants With Treatment-Emergent Adverse Events, Adverse Events of Special Interest (AESI) and Treatment-related Adverse Events According to NCI-CTCAE v4.03 | Participants with Study-drug related TEAEs | 10 Participants |
| Avelumab 20 mg/kg | Number of Participants With Treatment-Emergent Adverse Events, Adverse Events of Special Interest (AESI) and Treatment-related Adverse Events According to NCI-CTCAE v4.03 | Participants with any TEAEs | 15 Participants |
| Avelumab 20 mg/kg | Number of Participants With Treatment-Emergent Adverse Events, Adverse Events of Special Interest (AESI) and Treatment-related Adverse Events According to NCI-CTCAE v4.03 | Participants with Treatment-emergent IRR | 7 Participants |
| Avelumab 20 mg/kg | Number of Participants With Treatment-Emergent Adverse Events, Adverse Events of Special Interest (AESI) and Treatment-related Adverse Events According to NCI-CTCAE v4.03 | Participants with Treatment-emergent irAE | 1 Participants |
Secondary
Overall Survival (OS)
Overall Survival was defined as the time from date of first dose of study drug to the date of death due to any cause. For participants who were still alive at the time of data analysis or who were lost to follow-up, OS time was censored at the date of last contact. OS was measured using Kaplan-Meier (KM) estimates.
Time frame: Time from first administration of study drug up to 1182 days
Population: Full analysis set included all participants who received any dose of avelumab. Here, Number of participants analyzed signifies those participants who were evaluable for this outcome measure.
| Arm | Measure | Value (MEDIAN) | Dispersion |
|---|---|---|---|
| Avelumab 10 Miligram Per Kilogram (mg/kg) | Overall Survival (OS) | 4.4 Months | Full Range 1.51 |
| Avelumab 20 mg/kg | Overall Survival (OS) | 7.0 Months | Full Range 0.85 |
Secondary
Progression-Free Survival According to Response Evaluation Criteria in Solid Tumors (RECIST Version 1.1) and as Adjudicated by the Investigator
Progression-Free survival was defined as the time from first administration of study treatment until the first documentation of disease progression (PD) or death due to any cause, whichever occurred first. PD: 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. PFS was measured using Kaplan-Meier (KM) estimates.
Time frame: Time from first administration of study drug until the first documentation of PD or death, assessed up to 1182 days
Population: Full analysis set included all participants who received any dose of avelumab. Here, Number of participants analyzed signifies those participants who were evaluable for this outcome measure.
| Arm | Measure | Value (MEDIAN) | Dispersion |
|---|---|---|---|
| Avelumab 10 Miligram Per Kilogram (mg/kg) | Progression-Free Survival According to Response Evaluation Criteria in Solid Tumors (RECIST Version 1.1) and as Adjudicated by the Investigator | 7.5 Weeks | Full Range 6.57 |
| Avelumab 20 mg/kg | Progression-Free Survival According to Response Evaluation Criteria in Solid Tumors (RECIST Version 1.1) and as Adjudicated by the Investigator | 7.7 Weeks | Full Range 0.14 |
Secondary
Time to Response According to Response Evaluation Criteria in Solid Tumors (RECIST Version 1.1) and as Adjudicated by the Investigator
Time to response (TTR) was defined, for participants with an objective response, as the time from the start date of study treatment to the first documentation of OR (CR or PR) which was subsequently confirmed.
Time frame: Time from start of study treatment up to 1182 days
Population: Data could not be calculated as none of the participants showed confirmed objective response.