Trial Outcomes & Findings for Study of Avelumab and Cetuximab Plus Gemcitabine and Cisplatin in Participants With NSCLC (NCT NCT03717155)
NCT ID: NCT03717155
Last Updated: 2022-06-06
Results Overview
Confirmed BOR was defined as the percentage of participants who achieved confirmed complete responses (CR) or partial response (PR), according to RECIST version 1.1 assessed by the Investigator.CR: Disappearance of all evidence of target and non-target lesions. PR: At least 30 percent (%) reduction from baseline in the sum of the longest diameter (SLD) of all lesions. Stable disease (SD)= Neither sufficient increase to qualify for progression of disease (PD) nor sufficient shrinkage to qualify for PR. 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. Confirmed CR=as at least two determinations of CR at least 4 weeks apart with no PD. Confirmed PR=as at least 2 determinations of PR or better (PR followed by PR or PR followed by CR), at least 4 weeks apart (not qualifying for a CR) with no PD in between. Percentage of Participants with confirmed BOR were reported.
Recruitment status
COMPLETED
Study phase
PHASE2
Target enrollment
43 participants
Primary outcome timeframe
Time from the first dose of study drug until occurrence of PD, death due to any cause (assessed up to 612 days)
Results posted on
2022-06-06
Participant Flow
A total of 43 participants were enrolled in this study at different sites in Hungary, Serbia and Spain.
Participant milestones
| Measure |
Avelumab and Cetuximab
Participants received 800 milligrams Avelumab, 1250 milligrams per square meter (mg/m\^2) gemcitabine on Day 1 and Day 8, cisplatin at a dose of 75 mg/m\^2 on Day 1 along with 250 mg/m2 body surface area Cetuximab on Day 1 and 500 mg/m2 body surface area on Day 8 of each cycle as intravenous (IV) infusions up to maximum of 4 cycles (each cycle is of 3 weeks) until disease progression or unacceptable toxicities. In case of cisplatin toxicities, participants were switched to carboplatin at a dose of target area under the serum concentration-time curve of 5 (AUC 5) on Day 1 for the remainder of cycles. Subsequently participants were administered with avelumab and cetuximab as IV infusion at the dose of 800 mg and 500 mg/m\^2 respectively, every 2 weeks in the Maintenance phase until disease progression or unacceptable toxicities.
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|---|---|
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Overall Study
STARTED
|
43
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|
Overall Study
COMPLETED
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43
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Overall Study
NOT COMPLETED
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0
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Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Study of Avelumab and Cetuximab Plus Gemcitabine and Cisplatin in Participants With NSCLC
Baseline characteristics by cohort
| Measure |
Avelumab and Cetuximab
n=43 Participants
Participants received 800 milligrams Avelumab, 1250 milligrams per square meter (mg/m\^2) gemcitabine on Day 1 and Day 8, cisplatin at a dose of 75 mg/m\^2 on Day 1 along with 250 mg/m2 body surface area Cetuximab on Day 1 and 500 mg/m2 body surface area on Day 8 of each cycle as intravenous (IV) infusions up to maximum of 4 cycles (each cycle is of 3 weeks) until disease progression or unacceptable toxicities. In case of cisplatin toxicities, participants were switched to carboplatin at a dose of target area under the serum concentration-time curve of 5 (AUC 5) on Day 1 for the remainder of cycles. Subsequently participants were administered with avelumab and cetuximab as IV infusion at the dose of 800 mg and 500 mg/m\^2 respectively, every 2 weeks in the Maintenance phase until disease progression or unacceptable toxicities.
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|---|---|
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Age, Continuous
|
63 Years
STANDARD_DEVIATION 7.2 • n=5 Participants
|
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Sex: Female, Male
Female
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8 Participants
n=5 Participants
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Sex: Female, Male
Male
|
35 Participants
n=5 Participants
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|
Race (NIH/OMB)
American Indian or Alaska Native
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0 Participants
n=5 Participants
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|
Race (NIH/OMB)
Asian
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0 Participants
n=5 Participants
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|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants
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|
Race (NIH/OMB)
Black or African American
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0 Participants
n=5 Participants
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|
Race (NIH/OMB)
White
|
43 Participants
n=5 Participants
|
|
Race (NIH/OMB)
More than one race
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0 Participants
n=5 Participants
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|
Race (NIH/OMB)
Unknown or Not Reported
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0 Participants
n=5 Participants
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PRIMARY outcome
Timeframe: Time from the first dose of study drug until occurrence of PD, death due to any cause (assessed up to 612 days)Population: Full analysis set includes all participants who received at least one non-zero dose of any study treatment.
Confirmed BOR was defined as the percentage of participants who achieved confirmed complete responses (CR) or partial response (PR), according to RECIST version 1.1 assessed by the Investigator.CR: Disappearance of all evidence of target and non-target lesions. PR: At least 30 percent (%) reduction from baseline in the sum of the longest diameter (SLD) of all lesions. Stable disease (SD)= Neither sufficient increase to qualify for progression of disease (PD) nor sufficient shrinkage to qualify for PR. 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. Confirmed CR=as at least two determinations of CR at least 4 weeks apart with no PD. Confirmed PR=as at least 2 determinations of PR or better (PR followed by PR or PR followed by CR), at least 4 weeks apart (not qualifying for a CR) with no PD in between. Percentage of Participants with confirmed BOR were reported.
Outcome measures
| Measure |
Avelumab and Cetuximab
n=43 Participants
Participants received 800 milligrams Avelumab, 1250 milligrams per square meter (mg/m\^2) gemcitabine on Day 1 and Day 8, cisplatin at a dose of 75 mg/m\^2 on Day 1 along with 250 mg/m2 body surface area Cetuximab on Day 1 and 500 mg/m2 body surface area on Day 8 of each cycle as intravenous (IV) infusions up to maximum of 4 cycles (each cycle is of 3 weeks) until disease progression or unacceptable toxicities. In case of cisplatin toxicities, participants were switched to carboplatin at a dose of target area under the serum concentration-time curve of 5 (AUC 5) on Day 1 for the remainder of cycles. Subsequently participants were administered with avelumab and cetuximab as IV infusion at the dose of 800 mg and 500 mg/m\^2 respectively, every 2 weeks in the Maintenance phase until disease progression or unacceptable toxicities.
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|---|---|
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Percentage of Participants With Confirmed Best Objective Response (BOR) According to Response Evaluation Criteria In Solid Tumors (RECIST) Version 1.1 Assessed by Investigator
|
34.9 percentage of participants
Interval 21.0 to 50.9
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SECONDARY outcome
Timeframe: Time from the first dose of study drug assessed up to (941 days)Population: Safety analysis set included all participants who received at least one non-zero dose of any study treatment.
Adverse event (AE) was defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease 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.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. TEAE is defined as AEs starting or worsening after the first intake of the study drug. TEAEs include both Serious and non-serious TEAEs. irAEs included AEs that matches a preferred term on the list of pre-selected MedDRA terms. AEs with relationship to study treatment are reported as Treatment-related AEs. Treatment related AEs with grade 3 or more is also reported.
Outcome measures
| Measure |
Avelumab and Cetuximab
n=43 Participants
Participants received 800 milligrams Avelumab, 1250 milligrams per square meter (mg/m\^2) gemcitabine on Day 1 and Day 8, cisplatin at a dose of 75 mg/m\^2 on Day 1 along with 250 mg/m2 body surface area Cetuximab on Day 1 and 500 mg/m2 body surface area on Day 8 of each cycle as intravenous (IV) infusions up to maximum of 4 cycles (each cycle is of 3 weeks) until disease progression or unacceptable toxicities. In case of cisplatin toxicities, participants were switched to carboplatin at a dose of target area under the serum concentration-time curve of 5 (AUC 5) on Day 1 for the remainder of cycles. Subsequently participants were administered with avelumab and cetuximab as IV infusion at the dose of 800 mg and 500 mg/m\^2 respectively, every 2 weeks in the Maintenance phase until disease progression or unacceptable toxicities.
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Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Treatment-Related Adverse Events (AEs), Treatment-Related Grade >=3 TEAEs and Immune-related Treatment Emergent AEs (irTEAEs)
TEAEs
|
41 Participants
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Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Treatment-Related Adverse Events (AEs), Treatment-Related Grade >=3 TEAEs and Immune-related Treatment Emergent AEs (irTEAEs)
Treatment-Related AEs
|
38 Participants
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|
Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Treatment-Related Adverse Events (AEs), Treatment-Related Grade >=3 TEAEs and Immune-related Treatment Emergent AEs (irTEAEs)
Treatment Related Grade>=3 TEAEs
|
24 Participants
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Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Treatment-Related Adverse Events (AEs), Treatment-Related Grade >=3 TEAEs and Immune-related Treatment Emergent AEs (irTEAEs)
irTEAEs
|
13 Participants
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SECONDARY outcome
Timeframe: Time from the first dose of study drug until occurrence of PD, death due to any cause (assessed up to 737 days)Population: Full analysis set includes all participants who received at least one non-zero dose of any study treatment.
Progression free survival (PFS) is defined as the time (in months) from first treatment day to the date of the first documentation of objective progression of disease (PD) according to RECIST version 1.1 assessed by Investigator, or death due to any cause, whichever occurs first. PD is defined as at least a 20 percent (%) increase in the SLD, taking as reference the smallest SLD recorded from baseline or the appearance of 1 or more new lesions.
Outcome measures
| Measure |
Avelumab and Cetuximab
n=43 Participants
Participants received 800 milligrams Avelumab, 1250 milligrams per square meter (mg/m\^2) gemcitabine on Day 1 and Day 8, cisplatin at a dose of 75 mg/m\^2 on Day 1 along with 250 mg/m2 body surface area Cetuximab on Day 1 and 500 mg/m2 body surface area on Day 8 of each cycle as intravenous (IV) infusions up to maximum of 4 cycles (each cycle is of 3 weeks) until disease progression or unacceptable toxicities. In case of cisplatin toxicities, participants were switched to carboplatin at a dose of target area under the serum concentration-time curve of 5 (AUC 5) on Day 1 for the remainder of cycles. Subsequently participants were administered with avelumab and cetuximab as IV infusion at the dose of 800 mg and 500 mg/m\^2 respectively, every 2 weeks in the Maintenance phase until disease progression or unacceptable toxicities.
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|---|---|
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Progression-Free Survival (PFS) Time Per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1
|
6.1 Months
Interval 4.3 to 9.0
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SECONDARY outcome
Timeframe: Time from the first dose of study drug until occurrence of PD, death due to any cause or last tumor assessment (assessed up to 612 days)Population: Full analysis set included all participants who receive at least one non-zero dose of any study treatment. Here "Overall number of participants analyzed" signifies those participants who had confirmed CR or PR.
DOR is defined for participants with confirmed complete response (CR) or partial response (PR), as the time from first documentation of confirmed response to the date of first documentation of progression of disease (PD) according to RECIST version 1.1 (assessed by Investigator) or death due to any cause or tumor assessment. Duration of objective response was assessed using Kaplan-Meier analysis. 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 percent (%) increase in the SLD, taking as reference the smallest SLD recorded from baseline or the appearance of 1 or more new lesions.
Outcome measures
| Measure |
Avelumab and Cetuximab
n=15 Participants
Participants received 800 milligrams Avelumab, 1250 milligrams per square meter (mg/m\^2) gemcitabine on Day 1 and Day 8, cisplatin at a dose of 75 mg/m\^2 on Day 1 along with 250 mg/m2 body surface area Cetuximab on Day 1 and 500 mg/m2 body surface area on Day 8 of each cycle as intravenous (IV) infusions up to maximum of 4 cycles (each cycle is of 3 weeks) until disease progression or unacceptable toxicities. In case of cisplatin toxicities, participants were switched to carboplatin at a dose of target area under the serum concentration-time curve of 5 (AUC 5) on Day 1 for the remainder of cycles. Subsequently participants were administered with avelumab and cetuximab as IV infusion at the dose of 800 mg and 500 mg/m\^2 respectively, every 2 weeks in the Maintenance phase until disease progression or unacceptable toxicities.
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|---|---|
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Duration of Response (DOR)
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7.1 Months
Interval 4.2 to 12.5
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SECONDARY outcome
Timeframe: Pre-dose, 2 hours after end of infusion on Day 1, 8, 22 and 29; Pre-dose, 30 minutes after the end of infusion on Day 43, 50, 64, 71; Pre-dose, 3 hours after end of infusion on Day 85, 99, 113, 127, 169, 253, and 337Population: Pharmacokinetic (PK) analysis set included all participants who receive at least one dose of avelumab and/or cetuximab, have no important events affecting PK, and provide at least one measurable post-dose concentration. Number of Participants Analyzed=participants evaluable for this outcome and Number analyzed=participants evaluated at specified time point.
Ceoi is the serum concentration observed immediately at the end of infusion. This was taken directly from the observed Avelumab concentration-time data.
Outcome measures
| Measure |
Avelumab and Cetuximab
n=40 Participants
Participants received 800 milligrams Avelumab, 1250 milligrams per square meter (mg/m\^2) gemcitabine on Day 1 and Day 8, cisplatin at a dose of 75 mg/m\^2 on Day 1 along with 250 mg/m2 body surface area Cetuximab on Day 1 and 500 mg/m2 body surface area on Day 8 of each cycle as intravenous (IV) infusions up to maximum of 4 cycles (each cycle is of 3 weeks) until disease progression or unacceptable toxicities. In case of cisplatin toxicities, participants were switched to carboplatin at a dose of target area under the serum concentration-time curve of 5 (AUC 5) on Day 1 for the remainder of cycles. Subsequently participants were administered with avelumab and cetuximab as IV infusion at the dose of 800 mg and 500 mg/m\^2 respectively, every 2 weeks in the Maintenance phase until disease progression or unacceptable toxicities.
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|---|---|
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Immediate Observed Serum Concentration at End of Infusion (Ceoi) of Avelumab
Day 1
|
206 microgram per milliliter (mcg/mL)
Geometric Coefficient of Variation 26.6
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Immediate Observed Serum Concentration at End of Infusion (Ceoi) of Avelumab
Day 8
|
243 microgram per milliliter (mcg/mL)
Geometric Coefficient of Variation 23.8
|
|
Immediate Observed Serum Concentration at End of Infusion (Ceoi) of Avelumab
Day 22
|
234 microgram per milliliter (mcg/mL)
Geometric Coefficient of Variation 24.1
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|
Immediate Observed Serum Concentration at End of Infusion (Ceoi) of Avelumab
Day 29
|
282 microgram per milliliter (mcg/mL)
Geometric Coefficient of Variation 26.8
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Immediate Observed Serum Concentration at End of Infusion (Ceoi) of Avelumab
Day 43
|
237 microgram per milliliter (mcg/mL)
Geometric Coefficient of Variation 30.5
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Immediate Observed Serum Concentration at End of Infusion (Ceoi) of Avelumab
Day 50
|
259 microgram per milliliter (mcg/mL)
Geometric Coefficient of Variation 38.9
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|
Immediate Observed Serum Concentration at End of Infusion (Ceoi) of Avelumab
Day 64
|
214 microgram per milliliter (mcg/mL)
Geometric Coefficient of Variation 67.6
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|
Immediate Observed Serum Concentration at End of Infusion (Ceoi) of Avelumab
Day 71
|
244 microgram per milliliter (mcg/mL)
Geometric Coefficient of Variation 43.8
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|
Immediate Observed Serum Concentration at End of Infusion (Ceoi) of Avelumab
Day 85
|
223 microgram per milliliter (mcg/mL)
Geometric Coefficient of Variation 33.3
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Immediate Observed Serum Concentration at End of Infusion (Ceoi) of Avelumab
Day 99
|
202 microgram per milliliter (mcg/mL)
Geometric Coefficient of Variation 62.4
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Immediate Observed Serum Concentration at End of Infusion (Ceoi) of Avelumab
Day 113
|
234 microgram per milliliter (mcg/mL)
Geometric Coefficient of Variation 29.7
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Immediate Observed Serum Concentration at End of Infusion (Ceoi) of Avelumab
Day 127
|
222 microgram per milliliter (mcg/mL)
Geometric Coefficient of Variation 55.1
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Immediate Observed Serum Concentration at End of Infusion (Ceoi) of Avelumab
Day 169
|
245 microgram per milliliter (mcg/mL)
Geometric Coefficient of Variation 20.8
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Immediate Observed Serum Concentration at End of Infusion (Ceoi) of Avelumab
Day 253
|
249 microgram per milliliter (mcg/mL)
Geometric Coefficient of Variation 28.7
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Immediate Observed Serum Concentration at End of Infusion (Ceoi) of Avelumab
Day 337
|
246 microgram per milliliter (mcg/mL)
Geometric Coefficient of Variation 38.6
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SECONDARY outcome
Timeframe: Pre-dose, 2 hours after end of infusion on Day 1, 8, 22 and 29; Pre-dose, 30 minutes after the end of infusion on Day 43, 50, 64, 71; Pre-dose, 3 hours after end of infusion on Day 85, 99, 113, 127, 169, 253, and 337Population: PK analysis set included all participants who receive at least one dose of avelumab and/or cetuximab, have no important events affecting PK, and provide at least one measurable post-dose concentration. Number analyzed=participants evaluated at specified time point.
Ceoi is the serum concentration observed immediately at the end of infusion. This was taken directly from the observed cetuximab concentration-time data.
Outcome measures
| Measure |
Avelumab and Cetuximab
n=43 Participants
Participants received 800 milligrams Avelumab, 1250 milligrams per square meter (mg/m\^2) gemcitabine on Day 1 and Day 8, cisplatin at a dose of 75 mg/m\^2 on Day 1 along with 250 mg/m2 body surface area Cetuximab on Day 1 and 500 mg/m2 body surface area on Day 8 of each cycle as intravenous (IV) infusions up to maximum of 4 cycles (each cycle is of 3 weeks) until disease progression or unacceptable toxicities. In case of cisplatin toxicities, participants were switched to carboplatin at a dose of target area under the serum concentration-time curve of 5 (AUC 5) on Day 1 for the remainder of cycles. Subsequently participants were administered with avelumab and cetuximab as IV infusion at the dose of 800 mg and 500 mg/m\^2 respectively, every 2 weeks in the Maintenance phase until disease progression or unacceptable toxicities.
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|---|---|
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Immediate Observed Serum Concentration at End of Infusion (Ceoi) of Cetuximab
Day 1
|
109 mcg/mL
Geometric Coefficient of Variation 50.7
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Immediate Observed Serum Concentration at End of Infusion (Ceoi) of Cetuximab
Day 8
|
198 mcg/mL
Geometric Coefficient of Variation 86.6
|
|
Immediate Observed Serum Concentration at End of Infusion (Ceoi) of Cetuximab
Day 22
|
124 mcg/mL
Geometric Coefficient of Variation 54.4
|
|
Immediate Observed Serum Concentration at End of Infusion (Ceoi) of Cetuximab
Day 29
|
260 mcg/mL
Geometric Coefficient of Variation 25.0
|
|
Immediate Observed Serum Concentration at End of Infusion (Ceoi) of Cetuximab
Day 43
|
154 mcg/mL
Geometric Coefficient of Variation 32.7
|
|
Immediate Observed Serum Concentration at End of Infusion (Ceoi) of Cetuximab
Day 50
|
238 mcg/mL
Geometric Coefficient of Variation 28.9
|
|
Immediate Observed Serum Concentration at End of Infusion (Ceoi) of Cetuximab
Day 64
|
159 mcg/mL
Geometric Coefficient of Variation 36.1
|
|
Immediate Observed Serum Concentration at End of Infusion (Ceoi) of Cetuximab
Day 71
|
262 mcg/mL
Geometric Coefficient of Variation 25.1
|
|
Immediate Observed Serum Concentration at End of Infusion (Ceoi) of Cetuximab
Day 85
|
239 mcg/mL
Geometric Coefficient of Variation 38.4
|
|
Immediate Observed Serum Concentration at End of Infusion (Ceoi) of Cetuximab
Day 99
|
252 mcg/mL
Geometric Coefficient of Variation 21.1
|
|
Immediate Observed Serum Concentration at End of Infusion (Ceoi) of Cetuximab
Day 113
|
250 mcg/mL
Geometric Coefficient of Variation 20.4
|
|
Immediate Observed Serum Concentration at End of Infusion (Ceoi) of Cetuximab
Day 127
|
245 mcg/mL
Geometric Coefficient of Variation 55.8
|
|
Immediate Observed Serum Concentration at End of Infusion (Ceoi) of Cetuximab
Day 169
|
297 mcg/mL
Geometric Coefficient of Variation 29.2
|
|
Immediate Observed Serum Concentration at End of Infusion (Ceoi) of Cetuximab
Day 253
|
269 mcg/mL
Geometric Coefficient of Variation 34.4
|
|
Immediate Observed Serum Concentration at End of Infusion (Ceoi) of Cetuximab
Day 337
|
304 mcg/mL
Geometric Coefficient of Variation 37.3
|
SECONDARY outcome
Timeframe: Pre-dose: Day 8, Day 22, Day 29, Day 43, Day 50, Day 64, Day 71, Day 85, Day 99, Day 113, Day 127, Day 169, Day 253 and Day 337Population: PK analysis set included all participants who receive at least one dose of avelumab and/or cetuximab, have no important events affecting PK, and provide at least one measurable post-dose concentration. Number of Participants Analyzed=participants evaluable for this outcome and Number analyzed=participants evaluated at specified time point.
Ctrough is the serum concentration observed immediately before next dosing.
Outcome measures
| Measure |
Avelumab and Cetuximab
n=35 Participants
Participants received 800 milligrams Avelumab, 1250 milligrams per square meter (mg/m\^2) gemcitabine on Day 1 and Day 8, cisplatin at a dose of 75 mg/m\^2 on Day 1 along with 250 mg/m2 body surface area Cetuximab on Day 1 and 500 mg/m2 body surface area on Day 8 of each cycle as intravenous (IV) infusions up to maximum of 4 cycles (each cycle is of 3 weeks) until disease progression or unacceptable toxicities. In case of cisplatin toxicities, participants were switched to carboplatin at a dose of target area under the serum concentration-time curve of 5 (AUC 5) on Day 1 for the remainder of cycles. Subsequently participants were administered with avelumab and cetuximab as IV infusion at the dose of 800 mg and 500 mg/m\^2 respectively, every 2 weeks in the Maintenance phase until disease progression or unacceptable toxicities.
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|---|---|
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Serum Trough Concentration Levels (Ctrough) of Avelumab
Day 8
|
28.8 mcg/mL
Geometric Coefficient of Variation 82.7
|
|
Serum Trough Concentration Levels (Ctrough) of Avelumab
Day 22
|
13.6 mcg/mL
Geometric Coefficient of Variation 97.1
|
|
Serum Trough Concentration Levels (Ctrough) of Avelumab
Day 29
|
42.4 mcg/mL
Geometric Coefficient of Variation 147.8
|
|
Serum Trough Concentration Levels (Ctrough) of Avelumab
Day 43
|
15.6 mcg/mL
Geometric Coefficient of Variation 115.1
|
|
Serum Trough Concentration Levels (Ctrough) of Avelumab
Day 50
|
56.4 mcg/mL
Geometric Coefficient of Variation 77.9
|
|
Serum Trough Concentration Levels (Ctrough) of Avelumab
Day 64
|
19.7 mcg/mL
Geometric Coefficient of Variation 145.7
|
|
Serum Trough Concentration Levels (Ctrough) of Avelumab
Day 71
|
58.2 mcg/mL
Geometric Coefficient of Variation 62.5
|
|
Serum Trough Concentration Levels (Ctrough) of Avelumab
Day 85
|
21.5 mcg/mL
Geometric Coefficient of Variation 70.9
|
|
Serum Trough Concentration Levels (Ctrough) of Avelumab
Day 99
|
21.2 mcg/mL
Geometric Coefficient of Variation 75.4
|
|
Serum Trough Concentration Levels (Ctrough) of Avelumab
Day 113
|
19.4 mcg/mL
Geometric Coefficient of Variation 78.5
|
|
Serum Trough Concentration Levels (Ctrough) of Avelumab
Day 127
|
18.1 mcg/mL
Geometric Coefficient of Variation 107.6
|
|
Serum Trough Concentration Levels (Ctrough) of Avelumab
Day 169
|
19.3 mcg/mL
Geometric Coefficient of Variation 67.2
|
|
Serum Trough Concentration Levels (Ctrough) of Avelumab
Day 253
|
17.0 mcg/mL
Geometric Coefficient of Variation 80.1
|
|
Serum Trough Concentration Levels (Ctrough) of Avelumab
Day 337
|
20.8 mcg/mL
Geometric Coefficient of Variation 55.9
|
SECONDARY outcome
Timeframe: Pre-dose: Day 8, Day 22, Day 29, Day 43, Day 50, Day 64, Day 71, Day 85, Day 99, Day 113, Day 127, Day 169, Day 253 and Day 337Population: PK analysis set included all participants who receive at least one dose of avelumab and/or cetuximab, have no important events affecting PK, and provide at least one measurable post-dose concentration. Number of Participants Analyzed=participants evaluable for this outcome and Number analyzed=participants evaluated at specified time point.
Ctrough is the serum concentration observed immediately before next dosing.
Outcome measures
| Measure |
Avelumab and Cetuximab
n=32 Participants
Participants received 800 milligrams Avelumab, 1250 milligrams per square meter (mg/m\^2) gemcitabine on Day 1 and Day 8, cisplatin at a dose of 75 mg/m\^2 on Day 1 along with 250 mg/m2 body surface area Cetuximab on Day 1 and 500 mg/m2 body surface area on Day 8 of each cycle as intravenous (IV) infusions up to maximum of 4 cycles (each cycle is of 3 weeks) until disease progression or unacceptable toxicities. In case of cisplatin toxicities, participants were switched to carboplatin at a dose of target area under the serum concentration-time curve of 5 (AUC 5) on Day 1 for the remainder of cycles. Subsequently participants were administered with avelumab and cetuximab as IV infusion at the dose of 800 mg and 500 mg/m\^2 respectively, every 2 weeks in the Maintenance phase until disease progression or unacceptable toxicities.
|
|---|---|
|
Serum Trough Concentration Levels (Ctrough) of Cetuximab
Day 8
|
12.1 mcg/mL
Geometric Coefficient of Variation 90.0
|
|
Serum Trough Concentration Levels (Ctrough) of Cetuximab
Day 22
|
12.8 mcg/mL
Geometric Coefficient of Variation 63.7
|
|
Serum Trough Concentration Levels (Ctrough) of Cetuximab
Day 29
|
22.8 mcg/mL
Geometric Coefficient of Variation 73.3
|
|
Serum Trough Concentration Levels (Ctrough) of Cetuximab
Day 43
|
25.6 mcg/mL
Geometric Coefficient of Variation 103.7
|
|
Serum Trough Concentration Levels (Ctrough) of Cetuximab
Day 50
|
23.9 mcg/mL
Geometric Coefficient of Variation 118.1
|
|
Serum Trough Concentration Levels (Ctrough) of Cetuximab
Day 64
|
17.2 mcg/mL
Geometric Coefficient of Variation 157.9
|
|
Serum Trough Concentration Levels (Ctrough) of Cetuximab
Day 71
|
35.4 mcg/mL
Geometric Coefficient of Variation 110.4
|
|
Serum Trough Concentration Levels (Ctrough) of Cetuximab
Day 85
|
26.5 mcg/mL
Geometric Coefficient of Variation 119.4
|
|
Serum Trough Concentration Levels (Ctrough) of Cetuximab
Day 99
|
22.6 mcg/mL
Geometric Coefficient of Variation 117.3
|
|
Serum Trough Concentration Levels (Ctrough) of Cetuximab
Day 113
|
35.0 mcg/mL
Geometric Coefficient of Variation 59.0
|
|
Serum Trough Concentration Levels (Ctrough) of Cetuximab
Day 127
|
38.0 mcg/mL
Geometric Coefficient of Variation 63.6
|
|
Serum Trough Concentration Levels (Ctrough) of Cetuximab
Day 169
|
40.4 mcg/mL
Geometric Coefficient of Variation 62.2
|
|
Serum Trough Concentration Levels (Ctrough) of Cetuximab
Day 253
|
31.9 mcg/mL
Geometric Coefficient of Variation 237.7
|
|
Serum Trough Concentration Levels (Ctrough) of Cetuximab
Day 337
|
28.9 mcg/mL
Geometric Coefficient of Variation 204.9
|
SECONDARY outcome
Timeframe: Time from the first dose of study drug until occurrence of death due to any cause (assessed up to 941 days)Population: Full analysis set includes all participants who received at least one non-zero dose of any study treatment.
OS is defined as the time from the first treatment day to the date of death due to any cause. Overall survival was assessed using Kaplan-Meier analysis.
Outcome measures
| Measure |
Avelumab and Cetuximab
n=43 Participants
Participants received 800 milligrams Avelumab, 1250 milligrams per square meter (mg/m\^2) gemcitabine on Day 1 and Day 8, cisplatin at a dose of 75 mg/m\^2 on Day 1 along with 250 mg/m2 body surface area Cetuximab on Day 1 and 500 mg/m2 body surface area on Day 8 of each cycle as intravenous (IV) infusions up to maximum of 4 cycles (each cycle is of 3 weeks) until disease progression or unacceptable toxicities. In case of cisplatin toxicities, participants were switched to carboplatin at a dose of target area under the serum concentration-time curve of 5 (AUC 5) on Day 1 for the remainder of cycles. Subsequently participants were administered with avelumab and cetuximab as IV infusion at the dose of 800 mg and 500 mg/m\^2 respectively, every 2 weeks in the Maintenance phase until disease progression or unacceptable toxicities.
|
|---|---|
|
Overall Survival (OS)
|
10.1 Months
Interval 8.6 to 14.5
|
SECONDARY outcome
Timeframe: Pre-dose up to 149 daysPopulation: ADA analysis set included all participants who received at least 1 dose of avelumab and/or cetuximab and have at least 1 valid ADA result.
The detection of antibodies to avelumab was performed using a validated immunoassay method with tiered testing of screening, confirmatory and titration. Number of participants with positive anti-drug antibody (ADA) of avelumab were reported.
Outcome measures
| Measure |
Avelumab and Cetuximab
n=43 Participants
Participants received 800 milligrams Avelumab, 1250 milligrams per square meter (mg/m\^2) gemcitabine on Day 1 and Day 8, cisplatin at a dose of 75 mg/m\^2 on Day 1 along with 250 mg/m2 body surface area Cetuximab on Day 1 and 500 mg/m2 body surface area on Day 8 of each cycle as intravenous (IV) infusions up to maximum of 4 cycles (each cycle is of 3 weeks) until disease progression or unacceptable toxicities. In case of cisplatin toxicities, participants were switched to carboplatin at a dose of target area under the serum concentration-time curve of 5 (AUC 5) on Day 1 for the remainder of cycles. Subsequently participants were administered with avelumab and cetuximab as IV infusion at the dose of 800 mg and 500 mg/m\^2 respectively, every 2 weeks in the Maintenance phase until disease progression or unacceptable toxicities.
|
|---|---|
|
Number of Participants With Positive Anti-Drug Antibody (ADA) of Avelumab
|
7 Participants
|
SECONDARY outcome
Timeframe: Pre-dose up to 149 daysPopulation: ADA analysis set included all participants who received at least 1 dose of avelumab and/or cetuximab and have at least 1 valid ADA result.
The detection of antibodies to cetuximab was performed using a validated immunoassay method with tiered testing of screening, confirmatory and titration. Number of participants with positive anti-drug antibody (ADA) of cetuximab were reported.
Outcome measures
| Measure |
Avelumab and Cetuximab
n=43 Participants
Participants received 800 milligrams Avelumab, 1250 milligrams per square meter (mg/m\^2) gemcitabine on Day 1 and Day 8, cisplatin at a dose of 75 mg/m\^2 on Day 1 along with 250 mg/m2 body surface area Cetuximab on Day 1 and 500 mg/m2 body surface area on Day 8 of each cycle as intravenous (IV) infusions up to maximum of 4 cycles (each cycle is of 3 weeks) until disease progression or unacceptable toxicities. In case of cisplatin toxicities, participants were switched to carboplatin at a dose of target area under the serum concentration-time curve of 5 (AUC 5) on Day 1 for the remainder of cycles. Subsequently participants were administered with avelumab and cetuximab as IV infusion at the dose of 800 mg and 500 mg/m\^2 respectively, every 2 weeks in the Maintenance phase until disease progression or unacceptable toxicities.
|
|---|---|
|
Number of Participants With Positive Anti-Drug Antibody (ADA) of Cetuximab
|
1 Participants
|
Adverse Events
Avelumab and Cetuximab
Serious events: 20 serious events
Other events: 39 other events
Deaths: 30 deaths
Serious adverse events
| Measure |
Avelumab and Cetuximab
n=43 participants at risk
Participants received 800 milligrams Avelumab, 1250 milligrams per square meter (mg/m\^2) gemcitabine on Day 1 and Day 8, cisplatin at a dose of 75 mg/m\^2 on Day 1 along with 250 mg/m2 body surface area Cetuximab on Day 1 and 500 mg/m2 body surface area on Day 8 of each cycle as intravenous (IV) infusions up to maximum of 4 cycles (each cycle is of 3 weeks) until disease progression or unacceptable toxicities. In case of cisplatin toxicities, participants were switched to carboplatin at a dose of target area under the serum concentration-time curve of 5 (AUC 5) on Day 1 for the remainder of cycles. Subsequently participants were administered with avelumab and cetuximab as IV infusion at the dose of 800 mg and 500 mg/m\^2 respectively, every 2 weeks in the Maintenance phase until disease progression or unacceptable toxicities.
|
|---|---|
|
Blood and lymphatic system disorders
Anaemia
|
4.7%
2/43 • Time from the first dose of study drug until 941 days.
|
|
Blood and lymphatic system disorders
Neutropenia
|
2.3%
1/43 • Time from the first dose of study drug until 941 days.
|
|
Blood and lymphatic system disorders
Thrombocytopenia
|
2.3%
1/43 • Time from the first dose of study drug until 941 days.
|
|
General disorders
Death
|
2.3%
1/43 • Time from the first dose of study drug until 941 days.
|
|
General disorders
Disease progression
|
9.3%
4/43 • Time from the first dose of study drug until 941 days.
|
|
General disorders
Non-cardiac chest pain
|
2.3%
1/43 • Time from the first dose of study drug until 941 days.
|
|
Immune system disorders
Anaphylactic reaction
|
2.3%
1/43 • Time from the first dose of study drug until 941 days.
|
|
Infections and infestations
Lower respiratory tract infection
|
2.3%
1/43 • Time from the first dose of study drug until 941 days.
|
|
Infections and infestations
Pneumonia
|
2.3%
1/43 • Time from the first dose of study drug until 941 days.
|
|
Investigations
Blood creatinine increased
|
2.3%
1/43 • Time from the first dose of study drug until 941 days.
|
|
Metabolism and nutrition disorders
Dehydration
|
2.3%
1/43 • Time from the first dose of study drug until 941 days.
|
|
Metabolism and nutrition disorders
Hypomagnesaemia
|
2.3%
1/43 • Time from the first dose of study drug until 941 days.
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
2.3%
1/43 • Time from the first dose of study drug until 941 days.
|
|
Nervous system disorders
Seizure
|
2.3%
1/43 • Time from the first dose of study drug until 941 days.
|
|
Renal and urinary disorders
Acute kidney injury
|
2.3%
1/43 • Time from the first dose of study drug until 941 days.
|
|
Renal and urinary disorders
Renal failure
|
2.3%
1/43 • Time from the first dose of study drug until 941 days.
|
|
Renal and urinary disorders
Renal impairment
|
2.3%
1/43 • Time from the first dose of study drug until 941 days.
|
|
Vascular disorders
Dry gangrene
|
2.3%
1/43 • Time from the first dose of study drug until 941 days.
|
|
Vascular disorders
Femoral artery embolism
|
2.3%
1/43 • Time from the first dose of study drug until 941 days.
|
|
Vascular disorders
Peripheral artery thrombosis
|
2.3%
1/43 • Time from the first dose of study drug until 941 days.
|
|
Cardiac disorders
Tachycardia
|
2.3%
1/43 • Time from the first dose of study drug until 941 days.
|
Other adverse events
| Measure |
Avelumab and Cetuximab
n=43 participants at risk
Participants received 800 milligrams Avelumab, 1250 milligrams per square meter (mg/m\^2) gemcitabine on Day 1 and Day 8, cisplatin at a dose of 75 mg/m\^2 on Day 1 along with 250 mg/m2 body surface area Cetuximab on Day 1 and 500 mg/m2 body surface area on Day 8 of each cycle as intravenous (IV) infusions up to maximum of 4 cycles (each cycle is of 3 weeks) until disease progression or unacceptable toxicities. In case of cisplatin toxicities, participants were switched to carboplatin at a dose of target area under the serum concentration-time curve of 5 (AUC 5) on Day 1 for the remainder of cycles. Subsequently participants were administered with avelumab and cetuximab as IV infusion at the dose of 800 mg and 500 mg/m\^2 respectively, every 2 weeks in the Maintenance phase until disease progression or unacceptable toxicities.
|
|---|---|
|
Blood and lymphatic system disorders
Anaemia
|
44.2%
19/43 • Time from the first dose of study drug until 941 days.
|
|
Blood and lymphatic system disorders
Leukopenia
|
11.6%
5/43 • Time from the first dose of study drug until 941 days.
|
|
Blood and lymphatic system disorders
Neutropenia
|
34.9%
15/43 • Time from the first dose of study drug until 941 days.
|
|
Blood and lymphatic system disorders
Thrombocytopenia
|
23.3%
10/43 • Time from the first dose of study drug until 941 days.
|
|
Gastrointestinal disorders
Diarrhoea
|
11.6%
5/43 • Time from the first dose of study drug until 941 days.
|
|
Gastrointestinal disorders
Nausea
|
27.9%
12/43 • Time from the first dose of study drug until 941 days.
|
|
Gastrointestinal disorders
Vomiting
|
16.3%
7/43 • Time from the first dose of study drug until 941 days.
|
|
General disorders
Asthenia
|
27.9%
12/43 • Time from the first dose of study drug until 941 days.
|
|
General disorders
Fatigue
|
16.3%
7/43 • Time from the first dose of study drug until 941 days.
|
|
General disorders
Oedema peripheral
|
7.0%
3/43 • Time from the first dose of study drug until 941 days.
|
|
General disorders
Pyrexia
|
14.0%
6/43 • Time from the first dose of study drug until 941 days.
|
|
Infections and infestations
Nasopharyngitis
|
7.0%
3/43 • Time from the first dose of study drug until 941 days.
|
|
Infections and infestations
Respiratory tract infection
|
7.0%
3/43 • Time from the first dose of study drug until 941 days.
|
|
Investigations
Alanine aminotransferase increased
|
14.0%
6/43 • Time from the first dose of study drug until 941 days.
|
|
Investigations
Amylase increased
|
11.6%
5/43 • Time from the first dose of study drug until 941 days.
|
|
Investigations
Aspartate aminotransferase increased
|
9.3%
4/43 • Time from the first dose of study drug until 941 days.
|
|
Investigations
Blood creatinine increased
|
11.6%
5/43 • Time from the first dose of study drug until 941 days.
|
|
Investigations
Neutrophil count decreased
|
7.0%
3/43 • Time from the first dose of study drug until 941 days.
|
|
Investigations
Transaminases increased
|
9.3%
4/43 • Time from the first dose of study drug until 941 days.
|
|
Metabolism and nutrition disorders
Decreased appetite
|
16.3%
7/43 • Time from the first dose of study drug until 941 days.
|
|
Metabolism and nutrition disorders
Hypocalcaemia
|
7.0%
3/43 • Time from the first dose of study drug until 941 days.
|
|
Metabolism and nutrition disorders
Hypomagnesaemia
|
37.2%
16/43 • Time from the first dose of study drug until 941 days.
|
|
Metabolism and nutrition disorders
Hyponatraemia
|
11.6%
5/43 • Time from the first dose of study drug until 941 days.
|
|
Metabolism and nutrition disorders
Hypophosphataemia
|
7.0%
3/43 • Time from the first dose of study drug until 941 days.
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea
|
7.0%
3/43 • Time from the first dose of study drug until 941 days.
|
|
Skin and subcutaneous tissue disorders
Dermatitis
|
7.0%
3/43 • Time from the first dose of study drug until 941 days.
|
|
Skin and subcutaneous tissue disorders
Dry skin
|
7.0%
3/43 • Time from the first dose of study drug until 941 days.
|
|
Skin and subcutaneous tissue disorders
Erythema
|
7.0%
3/43 • Time from the first dose of study drug until 941 days.
|
|
Skin and subcutaneous tissue disorders
Rash
|
51.2%
22/43 • Time from the first dose of study drug until 941 days.
|
|
Skin and subcutaneous tissue disorders
Dermatitis acneiform
|
7.0%
3/43 • Time from the first dose of study drug until 941 days.
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
9.3%
4/43 • Time from the first dose of study drug until 941 days.
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
7.0%
3/43 • Time from the first dose of study drug until 941 days.
|
Additional Information
Communication Center
Merck KGaA, Darmstadt, Germany
Phone: +49-6151-72-5200
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place