Trial Outcomes & Findings for A Study of Avelumab in Combination With Axitinib In Non-Small Cell Lung Cancer (NSCLC) or Urothelial Cancer (Javelin Medley VEGF) (NCT NCT03472560)

Last Updated: 2024-04-09

Results Overview

ORR: percentage of participants with a confirmed Complete Response (CR) or Partial Response (PR) based on investigator's assessment as per Response Evaluation Criteria in Solid Tumours (RECIST version \[v\] 1.1). Both CR and PR were confirmed by repeat assessments performed no less than 4 weeks after criteria for response was first met. Per RECIST v1.1: CR was defined as complete disappearance of all target lesions and non-target disease, with exception of nodal disease. All nodes, both target and non-target, must decrease to normal (short axis less than \[\<\]10 millimeter \[mm\]). No new lesions. PR was defined as greater than or equal to (\>=) 30 percent (%) decrease under baseline of sum of diameters of all target lesions. Short axis was used in sum for target nodes, while longest diameter was used in sum for all other target lesions. No unequivocal progression of non-target disease. No new lesions. Stable disease was defined as not qualifying for CR, PR, Progressive Disease.

Recruitment status

TERMINATED

Study phase

PHASE2

Target enrollment

61 participants

Primary outcome timeframe

Baseline up to 56 months

Results posted on

2024-04-09

Participant Flow

Participants diagnosed with advanced or metastatic non- small cell lung cancer (NSCLC) and received at least 1 prior platinum-containing therapy or participants with advanced or metastatic urothelial cancer (UC) and were treatment naïve and ineligible for cisplatin-containing chemotherapy for their advanced disease were enrolled.

A total of 104 participants were screened, out of which 43 participants failed screening and 61 participants were enrolled into the study.

Participant milestones

Participant milestones
Measure	NSCLC Avelumab + Axitinib Participants received avelumab 800 milligrams (mg) intravenous dose every two weeks, (Day 1 and 15) of each 28-day cycle in combination with axitinib 5 mg twice daily dose on a continuous dosing schedule.	UC Avelumab + Axitinib Participants received avelumab 800 mg intravenous dose every two weeks, (Day 1 and 15) of each 28-day cycle in combination with axitinib 5 mg twice daily dose on a continuous dosing schedule.
Overall Study STARTED	41	20
Overall Study COMPLETED	0	0
Overall Study NOT COMPLETED	41	20

Reasons for withdrawal

Reasons for withdrawal
Measure	NSCLC Avelumab + Axitinib Participants received avelumab 800 milligrams (mg) intravenous dose every two weeks, (Day 1 and 15) of each 28-day cycle in combination with axitinib 5 mg twice daily dose on a continuous dosing schedule.	UC Avelumab + Axitinib Participants received avelumab 800 mg intravenous dose every two weeks, (Day 1 and 15) of each 28-day cycle in combination with axitinib 5 mg twice daily dose on a continuous dosing schedule.
Overall Study Subject transfer to continuation protocol	0	1
Overall Study Withdrawal by Subject	4	0
Overall Study Progressive disease	24	8
Overall Study Physician Decision	1	0
Overall Study Death	7	4
Overall Study Adverse Event	5	3
Overall Study Global deterioration of health status	0	4

Baseline Characteristics

A Study of Avelumab in Combination With Axitinib In Non-Small Cell Lung Cancer (NSCLC) or Urothelial Cancer (Javelin Medley VEGF)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	NSCLC Avelumab + Axitinib n=41 Participants Participants received avelumab 800 milligrams (mg) intravenous dose every two weeks, (Day 1 and 15) of each 28-day cycle in combination with axitinib 5 mg twice daily dose on a continuous dosing schedule.	UC Avelumab + Axitinib n=20 Participants Participants received avelumab 800 mg intravenous dose every two weeks, (Day 1 and 15) of each 28-day cycle in combination with axitinib 5 mg twice daily dose on a continuous dosing schedule.	Total n=61 Participants Total of all reporting groups
Age, Continuous	64.0 Years STANDARD_DEVIATION 8.93 • n=93 Participants	70.7 Years STANDARD_DEVIATION 8.66 • n=4 Participants	66.16 Years STANDARD_DEVIATION 9.33 • n=27 Participants
Sex: Female, Male Female	11 Participants n=93 Participants	8 Participants n=4 Participants	19 Participants n=27 Participants
Sex: Female, Male Male	30 Participants n=93 Participants	12 Participants n=4 Participants	42 Participants n=27 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	1 Participants n=93 Participants	2 Participants n=4 Participants	3 Participants n=27 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	40 Participants n=93 Participants	17 Participants n=4 Participants	57 Participants n=27 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=93 Participants	1 Participants n=4 Participants	1 Participants n=27 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants
Race (NIH/OMB) Asian	21 Participants n=93 Participants	1 Participants n=4 Participants	22 Participants n=27 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants
Race (NIH/OMB) Black or African American	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants
Race (NIH/OMB) White	20 Participants n=93 Participants	17 Participants n=4 Participants	37 Participants n=27 Participants
Race (NIH/OMB) More than one race	0 Participants n=93 Participants	1 Participants n=4 Participants	1 Participants n=27 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=93 Participants	1 Participants n=4 Participants	1 Participants n=27 Participants

PRIMARY outcome

Timeframe: Baseline up to 56 months

Population: Full Analysis Set included all participants who received at least one dose of avelumab and axitinib. Participants were classified according to the study treatment received.

Outcome measures

Outcome measures
Measure	NSCLC Avelumab + Axitinib n=41 Participants Participants received avelumab 800 milligrams (mg) intravenous dose every two weeks, (Day 1 and 15) of each 28-day cycle in combination with axitinib 5 mg twice daily dose on a continuous dosing schedule.	UC Avelumab + Axitinib n=20 Participants Participants received avelumab 800 mg intravenous dose every two weeks, (Day 1 and 15) of each 28-day cycle in combination with axitinib 5 mg twice daily dose on a continuous dosing schedule.
Percentage of Participants With Confirmed Objective Response- Objective Response Rate (ORR)	31.7 Percentage of participants Interval 18.1 to 48.1	10.0 Percentage of participants Interval 1.2 to 31.7

SECONDARY outcome

Timeframe: From first dose of study treatment (Day 1) up to 30 days post last dose of study treatment or start of new anti-cancer treatment -1 day (maximum up to 56 months)

Population: Safety analysis set included all participants who received at least one dose of study drug (avelumab or axitinib). Participants were classified according to the study treatment received.

An Adverse Event (AE) was any untoward medical occurrence attributed to study drug in a participant who received avelumab or axitinib. Treatment-emergent adverse events (TEAEs) were those events with onset dates occurring during the on-treatment period (the time from the first dose of study treatment through minimum 30 days post last dose of study treatment or start day of new anti-cancer treatment -1 day).

Outcome measures

Outcome measures
Measure	NSCLC Avelumab + Axitinib n=41 Participants Participants received avelumab 800 milligrams (mg) intravenous dose every two weeks, (Day 1 and 15) of each 28-day cycle in combination with axitinib 5 mg twice daily dose on a continuous dosing schedule.	UC Avelumab + Axitinib n=20 Participants Participants received avelumab 800 mg intravenous dose every two weeks, (Day 1 and 15) of each 28-day cycle in combination with axitinib 5 mg twice daily dose on a continuous dosing schedule.
Percentage of Participants With Treatment Emergent Adverse Events (TEAEs) During the On-Treatment Period	100.0 Percentage of Participants	100.0 Percentage of Participants

SECONDARY outcome

Timeframe: From first dose of study treatment (Day 1) up to 30 days post last dose of study treatment or start of new anti-cancer treatment -1 day (maximum up to 56 months)

Population: Safety analysis set included all participants who received at least one dose of study drug (avelumab or axitinib). Participants were classified according to the study treatment received. Here 'Overall Number of Participants Analyzed' signifies participants evaluable for this outcome measure.

The following hematology parameters were assessed: anemia, hemoglobin increased, international normalized ratio (INR) increased, lymphocyte count decreased, lymphocyte count increased, neutrophil count decreased, platelet count decreased and white blood cell decreased. Laboratory abnormality events were graded according to NCI CTCAE v 4.03 (grade 3= severe and grade 4= life-threatening). Categories with non-zero values are presented.

Outcome measures

Outcome measures
Measure	NSCLC Avelumab + Axitinib n=41 Participants Participants received avelumab 800 milligrams (mg) intravenous dose every two weeks, (Day 1 and 15) of each 28-day cycle in combination with axitinib 5 mg twice daily dose on a continuous dosing schedule.	UC Avelumab + Axitinib n=18 Participants Participants received avelumab 800 mg intravenous dose every two weeks, (Day 1 and 15) of each 28-day cycle in combination with axitinib 5 mg twice daily dose on a continuous dosing schedule.
Percentage of Participants With Hematology Test Results of Maximum National Cancer Institute; Common Terminology Criteria for Adverse Events (NCI CTCAE) Grade During the On-Treatment Period Platelet count decreased (Grade >=3)	0 Percentage of participants	5.6 Percentage of participants
Percentage of Participants With Hematology Test Results of Maximum National Cancer Institute; Common Terminology Criteria for Adverse Events (NCI CTCAE) Grade During the On-Treatment Period Lymphocyte count decreased (Grade >=3)	12.2 Percentage of participants	5.6 Percentage of participants
Percentage of Participants With Hematology Test Results of Maximum National Cancer Institute; Common Terminology Criteria for Adverse Events (NCI CTCAE) Grade During the On-Treatment Period Neutrophil count decreased (Grade >=3)	2.4 Percentage of participants	0 Percentage of participants
Percentage of Participants With Hematology Test Results of Maximum National Cancer Institute; Common Terminology Criteria for Adverse Events (NCI CTCAE) Grade During the On-Treatment Period White blood cell decreased (Grade >=3)	2.4 Percentage of participants	0 Percentage of participants

SECONDARY outcome

Timeframe: From first dose of study treatment (Day 1) up to 30 days post last dose of study treatment or start of new anti-cancer treatment -1 day (maximum up to 56 months)

The following chemistry parameters were assessed: alanine aminotransferase increased, alkaline phosphatase increased, aspartate aminotransferase increased, blood bilirubin increased, cholesterol high, creatine phosphokinase (CPK) increased, creatinine increased, gamma-glutamyl transferase (GGT) increased, hypercalcemia, hyperglycemia, hyperkalemia, hypermagnesemia, hypernatremia, hypertriglyceridemia, hypoalbuminemia, hypocalcemia, hypoglycemia, hypokalemia, hypomagnesemia, hyponatremia, hypophosphatemia, lipase increased and serum amylase increased. Laboratory abnormalities were graded according CTCAE version 4.03 (grade 3= severe, grade 4= life-threatening and grade 5= death related). Categories with non-zero values are presented.

Outcome measures

Outcome measures
Measure	NSCLC Avelumab + Axitinib n=41 Participants Participants received avelumab 800 milligrams (mg) intravenous dose every two weeks, (Day 1 and 15) of each 28-day cycle in combination with axitinib 5 mg twice daily dose on a continuous dosing schedule.	UC Avelumab + Axitinib n=18 Participants Participants received avelumab 800 mg intravenous dose every two weeks, (Day 1 and 15) of each 28-day cycle in combination with axitinib 5 mg twice daily dose on a continuous dosing schedule.
Percentage of Participants With Chemistry Test Results of Maximum CTCAE Grade During the On-Treatment Period Alkaline phosphatase increased (Grade 3)	2.4 Percentage of participants	11.1 Percentage of participants
Percentage of Participants With Chemistry Test Results of Maximum CTCAE Grade During the On-Treatment Period Aspartate aminotransferase increased (Grade 3)	2.4 Percentage of participants	5.6 Percentage of participants
Percentage of Participants With Chemistry Test Results of Maximum CTCAE Grade During the On-Treatment Period Creatinine increased (Grade 3)	2.4 Percentage of participants	5.6 Percentage of participants
Percentage of Participants With Chemistry Test Results of Maximum CTCAE Grade During the On-Treatment Period Hyperglycemia (Grade 3)	4.9 Percentage of participants	5.6 Percentage of participants
Percentage of Participants With Chemistry Test Results of Maximum CTCAE Grade During the On-Treatment Period Hyperglycemia (Grade 4)	2.4 Percentage of participants	0 Percentage of participants
Percentage of Participants With Chemistry Test Results of Maximum CTCAE Grade During the On-Treatment Period Hyperkalemia (Grade 3)	7.3 Percentage of participants	0 Percentage of participants
Percentage of Participants With Chemistry Test Results of Maximum CTCAE Grade During the On-Treatment Period Hypermagnesemia (Grade 3)	2.4 Percentage of participants	0 Percentage of participants
Percentage of Participants With Chemistry Test Results of Maximum CTCAE Grade During the On-Treatment Period Hypermagnesemia (Grade 4)	0 Percentage of participants	5.6 Percentage of participants
Percentage of Participants With Chemistry Test Results of Maximum CTCAE Grade During the On-Treatment Period Hypoalbuminemia (Grade 3)	0 Percentage of participants	5.6 Percentage of participants
Percentage of Participants With Chemistry Test Results of Maximum CTCAE Grade During the On-Treatment Period Hypocalcemia (Grade 3)	4.9 Percentage of participants	5.6 Percentage of participants
Percentage of Participants With Chemistry Test Results of Maximum CTCAE Grade During the On-Treatment Period Hypoglycemia (Grade 4)	2.4 Percentage of participants	0 Percentage of participants
Percentage of Participants With Chemistry Test Results of Maximum CTCAE Grade During the On-Treatment Period Hypokalemia (Grade 3)	4.9 Percentage of participants	0 Percentage of participants
Percentage of Participants With Chemistry Test Results of Maximum CTCAE Grade During the On-Treatment Period Hypomagnesemia (Grade 3)	2.4 Percentage of participants	0 Percentage of participants
Percentage of Participants With Chemistry Test Results of Maximum CTCAE Grade During the On-Treatment Period Hypomagnesemia (Grade 4)	2.4 Percentage of participants	0 Percentage of participants
Percentage of Participants With Chemistry Test Results of Maximum CTCAE Grade During the On-Treatment Period Hyponatremia (Grade 3)	9.8 Percentage of participants	16.7 Percentage of participants
Percentage of Participants With Chemistry Test Results of Maximum CTCAE Grade During the On-Treatment Period Hyponatremia (Grade 4)	2.4 Percentage of participants	0 Percentage of participants
Percentage of Participants With Chemistry Test Results of Maximum CTCAE Grade During the On-Treatment Period Hypophosphatemia (Grade 3)	4.9 Percentage of participants	5.6 Percentage of participants
Percentage of Participants With Chemistry Test Results of Maximum CTCAE Grade During the On-Treatment Period Lipase increased (Grade 3)	10.3 Percentage of participants	6.3 Percentage of participants
Percentage of Participants With Chemistry Test Results of Maximum CTCAE Grade During the On-Treatment Period Lipase increased (Grade 4)	2.6 Percentage of participants	6.3 Percentage of participants
Percentage of Participants With Chemistry Test Results of Maximum CTCAE Grade During the On-Treatment Period Serum amylase increase (Grade 3)	2.5 Percentage of participants	12.5 Percentage of participants
Percentage of Participants With Chemistry Test Results of Maximum CTCAE Grade During the On-Treatment Period Alanine aminotransferase increased (Grade 3)	7.3 Percentage of participants	5.6 Percentage of participants
Percentage of Participants With Chemistry Test Results of Maximum CTCAE Grade During the On-Treatment Period Blood bilirubin increased (Grade 3)	2.4 Percentage of participants	0 Percentage of participants
Percentage of Participants With Chemistry Test Results of Maximum CTCAE Grade During the On-Treatment Period GGT increased (Grade 3)	7.5 Percentage of participants	18.8 Percentage of participants

SECONDARY outcome

Timeframe: From date of start of treatment until date of first documentation of objective tumor response (maximum up to 56 months)

Population: Full Analysis Set included all participants who received at least one dose of avelumab and axitinib. Participants were classified according to the study treatment received. Here, 'Overall Number of Participants Analyzed' signifies participants evaluable for this outcome measure.

TTR was defined as the time from the first dose of study treatment to the first documentation of objective tumor response documented in participants with confirmed objective response (CR or PR). CR was defined as complete disappearance of all target lesions and non-target disease, with the exception of nodal disease. All nodes, both target and non-target, must decrease to normal (short axis \<10 mm). No new lesions. PR was defined as \>=30% decrease under baseline of the sum of diameters of all target lesions. The short axis was used in the sum for target nodes, while the longest diameter was used in the sum for all other target lesions. No unequivocal progression of non-target disease. No new lesions. Analysis was performed using Kaplan-Meier method.

Outcome measures

Outcome measures
Measure	NSCLC Avelumab + Axitinib n=13 Participants Participants received avelumab 800 milligrams (mg) intravenous dose every two weeks, (Day 1 and 15) of each 28-day cycle in combination with axitinib 5 mg twice daily dose on a continuous dosing schedule.	UC Avelumab + Axitinib n=2 Participants Participants received avelumab 800 mg intravenous dose every two weeks, (Day 1 and 15) of each 28-day cycle in combination with axitinib 5 mg twice daily dose on a continuous dosing schedule.
Time to Tumor Response (TTR) in Participants With Confirmed CR or PR	1.9 Months Interval 1.8 to 5.3	2.8 Months Interval 1.8 to 3.7

SECONDARY outcome

Timeframe: From date of first documentation of objective tumor response to the first documentation of objective tumor progression or to death due to any cause, whichever occurred first (maximum up to 56 months)

Population: Full Analysis Set included all participants who receive at least one dose of avelumab and axitinib. Participants were classified according to the study treatment received. Here, 'Overall Number of Participants Analyzed' signifies participants evaluable for this outcome measure.

Duration of response was defined as the time from the first documentation of objective tumor response to the first documentation of objective tumor progression or to death due to any cause, whichever occurred first in participants with confirmed objective response (CR or PR). CR was defined as complete disappearance of all target lesions and non-target disease, with the exception of nodal disease. All nodes, both target and non-target, must decrease to normal (short axis \<10 mm). No new lesions. PR was defined as \>=30% decrease under baseline of the sum of diameters of all target lesions. The short axis was used in the sum for target nodes, while the longest diameter was used in the sum for all other target lesions. No unequivocal progression of non-target disease. No new lesions. Analysis was performed using Kaplan-Meier method.

Outcome measures

Outcome measures
Measure	NSCLC Avelumab + Axitinib n=13 Participants Participants received avelumab 800 milligrams (mg) intravenous dose every two weeks, (Day 1 and 15) of each 28-day cycle in combination with axitinib 5 mg twice daily dose on a continuous dosing schedule.	UC Avelumab + Axitinib n=2 Participants Participants received avelumab 800 mg intravenous dose every two weeks, (Day 1 and 15) of each 28-day cycle in combination with axitinib 5 mg twice daily dose on a continuous dosing schedule.
Duration of Response in Participants With Confirmed CR or PR	7.5 Months Interval 3.7 to 15.5	17.4 Months Interval 5.6 to 29.2

SECONDARY outcome

Timeframe: From start of study treatment until first documentation of PD or death due to any cause or censoring date (maximum of 24 months)

Population: Full Analysis Set included all participants who receive at least one dose of avelumab and axitinib. Participants were classified according to the study treatment received.

PFS was defined as the time from first dose of study treatment (ie, start date) to the date of progression of disease (PD) by RECIST v 1.1 or death due to any cause, whichever occurred first. PFS data was censored on the date of the last adequate tumor assessment for participants without an event (PD or death), for participants who started new anti-cancer treatment prior to an event, or for participants with an event after two or more missing tumor assessments. PD as per RECIST v1.1 for target lesions was defined as 20% increase in the sum of diameters of target measurable lesions above the smallest sum observed (over baseline if no decrease in the sum is observed during therapy), with a minimum absolute increase of 5 mm. For non-target lesions PD was defined as unequivocal progression of pre-existing lesions. Analysis was performed using Kaplan-Meier method.

Outcome measures

Outcome measures
Measure	NSCLC Avelumab + Axitinib n=41 Participants Participants received avelumab 800 milligrams (mg) intravenous dose every two weeks, (Day 1 and 15) of each 28-day cycle in combination with axitinib 5 mg twice daily dose on a continuous dosing schedule.	UC Avelumab + Axitinib n=20 Participants Participants received avelumab 800 mg intravenous dose every two weeks, (Day 1 and 15) of each 28-day cycle in combination with axitinib 5 mg twice daily dose on a continuous dosing schedule.
Progression Free Survival (PFS)	5.5 Months Interval 2.5 to 7.0	2.3 Months Interval 1.8 to 5.6

SECONDARY outcome

Timeframe: From date of start of study treatment until date of death or censoring date (maximum up to 56 months)

Population: Full Analysis Set included all participants who received at least one dose of avelumab and axitinib. Participants were classified according to the study treatment actually received.

Overall survival was defined as the time from the date of first study treatment to the date of death due to any cause. Participants last known to be alive were censored at date of last contact. Analysis was performed using Kaplan-Meier method.

Outcome measures

Outcome measures
Measure	NSCLC Avelumab + Axitinib n=41 Participants Participants received avelumab 800 milligrams (mg) intravenous dose every two weeks, (Day 1 and 15) of each 28-day cycle in combination with axitinib 5 mg twice daily dose on a continuous dosing schedule.	UC Avelumab + Axitinib n=20 Participants Participants received avelumab 800 mg intravenous dose every two weeks, (Day 1 and 15) of each 28-day cycle in combination with axitinib 5 mg twice daily dose on a continuous dosing schedule.
Overall Survival	15.4 Months Interval 8.0 to 26.9	16.8 Months Interval 2.3 to 35.4

SECONDARY outcome

Timeframe: Pre-dose, 1 hour post-dose on Cycle 1 Day 1, Day 15 and Cycle 2 Day 1

Population: The Pharmacokinetic (PK) parameter analysis set is a subset of the safety analysis set and included all participants who have at least one of the PK parameters of interest for avelumab or axitinib. Here, 'Overall Number of Participants Analyzed' signifies participants evaluable for this outcome measure. 'Number Analyzed' signifies number of participants evaluable for the specified rows.

Outcome measures

Outcome measures
Measure	NSCLC Avelumab + Axitinib n=35 Participants Participants received avelumab 800 milligrams (mg) intravenous dose every two weeks, (Day 1 and 15) of each 28-day cycle in combination with axitinib 5 mg twice daily dose on a continuous dosing schedule.	UC Avelumab + Axitinib n=15 Participants Participants received avelumab 800 mg intravenous dose every two weeks, (Day 1 and 15) of each 28-day cycle in combination with axitinib 5 mg twice daily dose on a continuous dosing schedule.
Maximum Observed Serum Concentration (Cmax) of Avelumab Cycle 1 (Day 1)	235.0 Microgram per milliliter Geometric Coefficient of Variation 26	206.3 Microgram per milliliter Geometric Coefficient of Variation 27
Maximum Observed Serum Concentration (Cmax) of Avelumab Cycle 1 (Day 15)	264.0 Microgram per milliliter Geometric Coefficient of Variation 34	163.9 Microgram per milliliter Geometric Coefficient of Variation 211
Maximum Observed Serum Concentration (Cmax) of Avelumab Cycle 2 (Day 1)	283.2 Microgram per milliliter Geometric Coefficient of Variation 24	260.4 Microgram per milliliter Geometric Coefficient of Variation 25

SECONDARY outcome

Timeframe: Pre-dose, 2 hour post-dose on Cycle 1 Day 15, Cycle 2 Day 1 and 15

Population: PK parameter analysis set is a subset of the safety analysis set and included all participants who have at least one of the PK parameters of interest for avelumab or axitinib. Here 'Overall Number of Participants Analyzed' signifies participants evaluable for this outcome measure. 'Number Analyzed' signifies number of participants evaluable for the specified rows.

Outcome measures

Outcome measures
Measure	NSCLC Avelumab + Axitinib n=16 Participants Participants received avelumab 800 milligrams (mg) intravenous dose every two weeks, (Day 1 and 15) of each 28-day cycle in combination with axitinib 5 mg twice daily dose on a continuous dosing schedule.	UC Avelumab + Axitinib n=5 Participants Participants received avelumab 800 mg intravenous dose every two weeks, (Day 1 and 15) of each 28-day cycle in combination with axitinib 5 mg twice daily dose on a continuous dosing schedule.
Cmax of Axitinib Cycle 1 (Day 15)	17.29 Microgram per milliliter Geometric Coefficient of Variation 198	14.64 Microgram per milliliter Geometric Coefficient of Variation 448
Cmax of Axitinib Cycle 2 (Day 1)	16.46 Microgram per milliliter Geometric Coefficient of Variation 91	5.206 Microgram per milliliter Geometric Coefficient of Variation 448
Cmax of Axitinib Cycle 2 (Day15)	10.64 Microgram per milliliter Geometric Coefficient of Variation 223	2.868 Microgram per milliliter Geometric Coefficient of Variation 24

SECONDARY outcome

Timeframe: Pre-dose on Cycle 1 Day 1, 15, Cycle 2 Day 1, Cycle 3 Day 15, Cycle 6 Day 15, Cycle 9 Day 15, and Cycle 12 Day 15

Outcome measures

Outcome measures
Measure	NSCLC Avelumab + Axitinib n=39 Participants Participants received avelumab 800 milligrams (mg) intravenous dose every two weeks, (Day 1 and 15) of each 28-day cycle in combination with axitinib 5 mg twice daily dose on a continuous dosing schedule.	UC Avelumab + Axitinib n=19 Participants Participants received avelumab 800 mg intravenous dose every two weeks, (Day 1 and 15) of each 28-day cycle in combination with axitinib 5 mg twice daily dose on a continuous dosing schedule.
Pre-dose Observed Serum Concentration (Ctrough) of Avelumab Cycle 1 (Day 1)	0 Microgram per milliliter Geometric Coefficient of Variation 0	0 Microgram per milliliter Geometric Coefficient of Variation 0
Pre-dose Observed Serum Concentration (Ctrough) of Avelumab Cycle 1 (Day 15)	19.46 Microgram per milliliter Geometric Coefficient of Variation 80	18.84 Microgram per milliliter Geometric Coefficient of Variation 101
Pre-dose Observed Serum Concentration (Ctrough) of Avelumab Cycle 2 (Day 1)	20.96 Microgram per milliliter Geometric Coefficient of Variation 119	19.62 Microgram per milliliter Geometric Coefficient of Variation 91
Pre-dose Observed Serum Concentration (Ctrough) of Avelumab Cycle 3 (Day 15)	28.22 Microgram per milliliter Geometric Coefficient of Variation 55	39.29 Microgram per milliliter Geometric Coefficient of Variation 36
Pre-dose Observed Serum Concentration (Ctrough) of Avelumab Cycle 6 (Day 15)	29.68 Microgram per milliliter Geometric Coefficient of Variation 52	43.30 Microgram per milliliter Geometric Coefficient of Variation 57
Pre-dose Observed Serum Concentration (Ctrough) of Avelumab Cycle 9 (Day 15)	32.84 Microgram per milliliter Geometric Coefficient of Variation 29	42.41 Microgram per milliliter Geometric Coefficient of Variation 47
Pre-dose Observed Serum Concentration (Ctrough) of Avelumab Cycle 12 (Day 15)	36.71 Microgram per milliliter Geometric Coefficient of Variation 50	39.01 Microgram per milliliter Geometric Coefficient of Variation 20

SECONDARY outcome

Timeframe: Pre-dose on Cycle 1 Day 15, Cycle 2 Day 1 and 15

Outcome measures

Outcome measures
Measure	NSCLC Avelumab + Axitinib n=29 Participants Participants received avelumab 800 milligrams (mg) intravenous dose every two weeks, (Day 1 and 15) of each 28-day cycle in combination with axitinib 5 mg twice daily dose on a continuous dosing schedule.	UC Avelumab + Axitinib n=14 Participants Participants received avelumab 800 mg intravenous dose every two weeks, (Day 1 and 15) of each 28-day cycle in combination with axitinib 5 mg twice daily dose on a continuous dosing schedule.
Ctrough of Axitinib Cycle 1 (Day 15)	7.923 Microgram per milliliter Geometric Coefficient of Variation 127	4.613 Microgram per milliliter Geometric Coefficient of Variation 231
Ctrough of Axitinib Cycle 2 (Day 1)	8.871 Microgram per milliliter Geometric Coefficient of Variation 123	5.247 Microgram per milliliter Geometric Coefficient of Variation 172
Ctrough of Axitinib Cycle 2 (Day 15)	6.455 Microgram per milliliter Geometric Coefficient of Variation 129	3.944 Microgram per milliliter Geometric Coefficient of Variation 172

SECONDARY outcome

Timeframe: Screening, up to 28 days prior to Day 1

Population: Biomarker analysis set is a subset of the safety analysis set and included participants who had at least one baseline biomarker assessment. Analysis sets was defined separately for blood-based and tumor tissue-based biomarkers. Here 'Overall Number of Participants Analyzed' signifies participants evaluable for this outcome measure.

PD-L1 status was defined as positive when PD-L1 staining of any intensity was observed in \>= 1% of the tumor cells. PD-L1 status was defined as negative when PD-L1 staining of any intensity was observed in \< 1% of the tumor cells.

Outcome measures

Outcome measures
Measure	NSCLC Avelumab + Axitinib n=32 Participants Participants received avelumab 800 milligrams (mg) intravenous dose every two weeks, (Day 1 and 15) of each 28-day cycle in combination with axitinib 5 mg twice daily dose on a continuous dosing schedule.	UC Avelumab + Axitinib n=16 Participants Participants received avelumab 800 mg intravenous dose every two weeks, (Day 1 and 15) of each 28-day cycle in combination with axitinib 5 mg twice daily dose on a continuous dosing schedule.
Number of Participants With Programmed Death-Ligand 1 (PD-L1) Status PD-L1 positive	8 Participants	5 Participants
Number of Participants With Programmed Death-Ligand 1 (PD-L1) Status PD-L1 negative	24 Participants	11 Participants

SECONDARY outcome

Timeframe: Screening, up to 28 days prior to Day 1

Population: Biomarker analysis set is a subset of the safety analysis set and included participants who had at least one baseline biomarker assessment. Analysis sets was defined separately for blood-based and tumor tissue-based biomarkers. Here, 'Number Analyzed' signifies number of participants evaluable for this outcome measure.

Mutational load within tumor tissue was defined as number per megabase of the genome, coding, base substitution, and indel mutations present in the sample. Mutational load was determined in whole blood samples using next generation deoxyribonucleic acid (DNA) sequencing followed by computational analysis.

Outcome measures

Outcome measures
Measure	NSCLC Avelumab + Axitinib n=24 Participants Participants received avelumab 800 milligrams (mg) intravenous dose every two weeks, (Day 1 and 15) of each 28-day cycle in combination with axitinib 5 mg twice daily dose on a continuous dosing schedule.	UC Avelumab + Axitinib n=15 Participants Participants received avelumab 800 mg intravenous dose every two weeks, (Day 1 and 15) of each 28-day cycle in combination with axitinib 5 mg twice daily dose on a continuous dosing schedule.
Tumour Mutational Burden (TMB) in Tumor Tissue	2.8 Mutations per megabase Standard Deviation 2.97	3.7 Mutations per megabase Standard Deviation 4.53

SECONDARY outcome

Timeframe: Screening, up to 28 days prior to Day 1

Population: Biomarker analysis set is a subset of the safety analysis set and included participants who have at least one baseline biomarker assessment. Analysis sets was defined separately for blood-based and tumor tissue-based biomarkers. Here 'Overall Number of Participants Analyzed' signifies participants evaluable for this outcome measure.

The immune response was measured by total T cell receptor (TCR) sequencing in peripheral blood and determined the characterization of immune repertoires. Fraction productive of cells is defined as the number of T cells within the total nucleated cell count (T cells and non-T cells).

Outcome measures

Outcome measures
Measure	NSCLC Avelumab + Axitinib n=15 Participants Participants received avelumab 800 milligrams (mg) intravenous dose every two weeks, (Day 1 and 15) of each 28-day cycle in combination with axitinib 5 mg twice daily dose on a continuous dosing schedule.	UC Avelumab + Axitinib n=10 Participants Participants received avelumab 800 mg intravenous dose every two weeks, (Day 1 and 15) of each 28-day cycle in combination with axitinib 5 mg twice daily dose on a continuous dosing schedule.
T-cell Receptor (TCR) Sequencing to Identify Fraction Productive of Cells	0.2 Proportion of T cells Standard Deviation 0.17	0.1 Proportion of T cells Standard Deviation 0.08

SECONDARY outcome

Timeframe: Pre-dose on Day 1 of Cycle 1

The immune response was measured by TCR sequencing in peripheral blood and determined the characterization of immune repertoires. Simpson clonality is calculated for a sample as the square root of Simpson's diversity index for all productive rearrangements. Values for clonality ranged from 0 to 1. Values near 1 represented samples with one or a few predominant rearrangements (monoclonal or oligoclonal samples) dominating the observed repertoire. Clonality values near 0 represented more polyclonal samples.

Outcome measures

Outcome measures
Measure	NSCLC Avelumab + Axitinib n=15 Participants Participants received avelumab 800 milligrams (mg) intravenous dose every two weeks, (Day 1 and 15) of each 28-day cycle in combination with axitinib 5 mg twice daily dose on a continuous dosing schedule.	UC Avelumab + Axitinib n=10 Participants Participants received avelumab 800 mg intravenous dose every two weeks, (Day 1 and 15) of each 28-day cycle in combination with axitinib 5 mg twice daily dose on a continuous dosing schedule.
T-cell Receptor (TCR) Sequencing to Identify Simpson Clonality	0.1 Index Standard Deviation 0.04	0.1 Index Standard Deviation 0.03

SECONDARY outcome

Timeframe: Pre-dose on Day 1 of Cycle 1

The immune response was measured by total TCR sequencing in peripheral blood and determined the characterization of immune repertoires.

Outcome measures

Outcome measures
Measure	NSCLC Avelumab + Axitinib n=15 Participants Participants received avelumab 800 milligrams (mg) intravenous dose every two weeks, (Day 1 and 15) of each 28-day cycle in combination with axitinib 5 mg twice daily dose on a continuous dosing schedule.	UC Avelumab + Axitinib n=10 Participants Participants received avelumab 800 mg intravenous dose every two weeks, (Day 1 and 15) of each 28-day cycle in combination with axitinib 5 mg twice daily dose on a continuous dosing schedule.
T-cell Receptor (TCR) Sequencing to Identify Total T Cells	1623.7 Cells Standard Deviation 1971.39	1168.4 Cells Standard Deviation 1450.51

SECONDARY outcome

Timeframe: Within 2 hours pre-dose on Cycle 1 Day 1,15, Cycle 2 Day 1; Day 15 of Cycle 3, 6, 9, 12, end of treatment and 30 days after last dose of study treatment (maximum up to 56 months)

Population: Immunogenicity analysis set is a subset of the safety analysis set and included participants who had at least one ADA assessment collected for avelumab. Here, 'Number Analyzed' signifies number of participants evaluable for the specified rows. Due to the low observed rate of the treatment-induced immunogenicity responses, none of the ADA positive samples was tested for the NAb assay.

ADA and nAb positive was defined as presence of at least one positive ADA and nAb sample, respectively. NAb analysis was planned to be conducted for ADA positive samples.

Outcome measures

Outcome measures
Measure	NSCLC Avelumab + Axitinib n=41 Participants Participants received avelumab 800 milligrams (mg) intravenous dose every two weeks, (Day 1 and 15) of each 28-day cycle in combination with axitinib 5 mg twice daily dose on a continuous dosing schedule.	UC Avelumab + Axitinib n=20 Participants Participants received avelumab 800 mg intravenous dose every two weeks, (Day 1 and 15) of each 28-day cycle in combination with axitinib 5 mg twice daily dose on a continuous dosing schedule.
Number of Participants With Positive Anti-drug Antibody (ADA) and Neutralizing Antibodies (nAb) Against Avelumab ADA ever-Positive	7 Participants	0 Participants

Adverse Events

NSCLC Avelumab + Axitinib

Serious events: 21 serious events

Other events: 41 other events

Deaths: 27 deaths

UC Avelumab + Axitinib

Serious events: 11 serious events

Other events: 17 other events

Deaths: 11 deaths

Serious adverse events

Other adverse events

Additional Information

Pfizer ClinicalTrials.gov Call Center

Pfizer Inc.

Phone: 1-800-718-1021

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee Pfizer has the right to review disclosures, requesting a delay of less than 60 days. Investigator will postpone single center publications until after disclosure of pooled data (all sites), less than 12 months from study completion/termination at all participating sites. Investigator may not disclose previously undisclosed confidential information other than study results.
Publication restrictions are in place

Restriction type: OTHER