Non-Small Cell Lung Cancer, Urothelial Cancer
Conditions
Keywords
Cancer, non-small cell lung cancer, non small cell lung cancer, NSCLC, lung cancer, urothelial cancer, bladder cancer, Avelumab, Bavencio, Axitinib, Inlyta
Brief summary
This is a Phase 2 study to evaluate the safety and efficacy of avelumab in combination with axitinib in patients with advanced or metastatic non-small cell lung cancer (NSCLC) who have received at least one prior platinum containing therapy, and in treatment naïve patients with advanced or metastatic urothelial cancer, who are ineligible for cisplatin containing chemotherapy for their advanced disease.
Interventions
IV treatment: Avelumab administered at 800 mg IV every two weeks
Oral treatment: Axitinib given 5 mg PO BID
Sponsors
Pfizer
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Non-small cell lung cancer (NSCLC) Cohort: Histologically or cytologically confirmed diagnosis of NSCLC that is locally advanced or metastatic; No activating EGFR mutations, ALK or ROS1 translocations/rearrangements where testing is standard of care; received at least 1 prior platinum-based chemotherapy regimen for locally advanced or metastatic NSCLC; No more than 2 prior lines of systemic therapy for locally advanced or metastatic disease (If disease progression occurred during or within 6 months after neoadjuvant/adjuvant chemotherapy or radiotherapy-chemotherapy, the regimen is counted as 1 prior treatment regimen towards the allowed limit of prior treatment regimens); Checkpoint inhibitor naïve. * Urothelial Cancer (UC) Cohort: Histologically or cytologically confirmed diagnosis of transitional cell carcinoma (TCC) of the urothelium (if mixed, more than 50% TCC component) including bladder, urethra, ureters, or renal pelvis that is locally advanced or metastatic; No prior systemic treatment for locally advanced or metastatic disease; Prior neoadjuvant or adjuvant therapy is permitted if disease progression occurred \>12 months after the completion of therapy; Checkpoint inhibitor naïve; Ineligible for receiving cisplatin-containing front-line chemotherapy based at least one of the following criteria: ECOG performance status (PS) 2; Renal dysfunction (defined as creatinine-clearance \<60 ml/min); Grade 2 peripheral neuropathy; Grade 2 hearing loss (hearing loss measured by audiometry of 25 decibels at two contiguous frequencies). * At least 1 measurable lesion by RECIST v1.1 not previously irradiated. * Availability of an archival FFPE tumor tissue block from primary diagnosis specimen or metastatic specimen or 15 unstained slides (10 minimum). If an archived sample is not available, a fresh tumor biopsy must be performed. * Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1. For UC patients, ECOG performance 2 is permitted (cisplatin ineligibility criterion)
Exclusion criteria
* Prior immunotherapy with an anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137, anti-OX-40, anti-GITR, anti-LAG-3, anti-TIM-3 or anti-CTLA-4 antibody (including ipilimumab). * Newly diagnosed brain metastases or known symptomatic brain metastases requiring steroids. * Radiologically documented evidence of major blood vessel invasion or encasement by cancer or intratumor cavitation, regardless of tumor histology. * Active autoimmune disease (that might deteriorate when receiving an immunostimulatory agent). * Current use of immunosuppressive medication (except for those listed in protocol). * Known prior severe hypersensitivity to the investigational products /monoclonal antibodies. * Known history of immune-mediated colitis, inflammatory bowel disease, immune-mediated pneumonitis, pulmonary fibrosis. * NCI CTCAE Grade 3 hemorrhage within 28 days prior to study enrollment.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Confirmed Objective Response- Objective Response Rate (ORR) | Baseline up to 56 months | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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 | 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 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. |
| Percentage of Participants With Chemistry Test Results of Maximum CTCAE Grade During the On-Treatment Period | 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. |
| Time to Tumor Response (TTR) in Participants With Confirmed CR or PR | From date of start of treatment until date of first documentation of objective tumor response (maximum up to 56 months) | 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. |
| Duration of Response in Participants With Confirmed CR or PR | 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) | 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. |
| Progression Free Survival (PFS) | From start of study treatment until first documentation of PD or death due to any cause or censoring date (maximum of 24 months) | 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. |
| Overall Survival | From date of start of study treatment until date of death or censoring date (maximum up to 56 months) | 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. |
| Maximum Observed Serum Concentration (Cmax) of Avelumab | Pre-dose, 1 hour post-dose on Cycle 1 Day 1, Day 15 and Cycle 2 Day 1 | — |
| Cmax of Axitinib | Pre-dose, 2 hour post-dose on Cycle 1 Day 15, Cycle 2 Day 1 and 15 | — |
| Percentage of Participants With Treatment Emergent Adverse Events (TEAEs) During the On-Treatment Period | 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) | 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). |
| Ctrough of Axitinib | Pre-dose on Cycle 1 Day 15, Cycle 2 Day 1 and 15 | — |
| Number of Participants With Programmed Death-Ligand 1 (PD-L1) Status | Screening, up to 28 days prior to Day 1 | 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. |
| Tumour Mutational Burden (TMB) in Tumor Tissue | Screening, up to 28 days prior to Day 1 | 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. |
| T-cell Receptor (TCR) Sequencing to Identify Fraction Productive of Cells | Screening, up to 28 days prior to Day 1 | 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). |
| T-cell Receptor (TCR) Sequencing to Identify Simpson Clonality | 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. |
| T-cell Receptor (TCR) Sequencing to Identify Total T Cells | 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. |
| Number of Participants With Positive Anti-drug Antibody (ADA) and Neutralizing Antibodies (nAb) Against Avelumab | 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) | 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. |
| Pre-dose Observed Serum Concentration (Ctrough) of Avelumab | 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 | — |
Countries
Hungary, Italy, Poland, Russia, South Korea, Spain, Taiwan, United States
Participant flow
Recruitment details
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.
Pre-assignment details
A total of 104 participants were screened, out of which 43 participants failed screening and 61 participants were enrolled into the study.
Participants by arm
| Arm | Count |
|---|---|
| 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. | 41 |
| 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. | 20 |
| Total | 61 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 5 | 3 |
| Overall Study | Death | 7 | 4 |
| Overall Study | Global deterioration of health status | 0 | 4 |
| Overall Study | Physician Decision | 1 | 0 |
| Overall Study | Progressive disease | 24 | 8 |
| Overall Study | Subject transfer to continuation protocol | 0 | 1 |
| Overall Study | Withdrawal by Subject | 4 | 0 |
Baseline characteristics
| Characteristic | UC Avelumab + Axitinib | Total | NSCLC Avelumab + Axitinib |
|---|---|---|---|
| Age, Continuous | 70.7 Years STANDARD_DEVIATION 8.66 | 66.16 Years STANDARD_DEVIATION 9.33 | 64.0 Years STANDARD_DEVIATION 8.93 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 2 Participants | 3 Participants | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 17 Participants | 57 Participants | 40 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 1 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants | 22 Participants | 21 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 1 Participants | 1 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 | 1 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) White | 17 Participants | 37 Participants | 20 Participants |
| Sex: Female, Male Female | 8 Participants | 19 Participants | 11 Participants |
| Sex: Female, Male Male | 12 Participants | 42 Participants | 30 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 27 / 41 | 11 / 20 |
| other Total, other adverse events | 41 / 41 | 17 / 20 |
| serious Total, serious adverse events | 21 / 41 | 11 / 20 |
Outcome results
Primary
Percentage of Participants With Confirmed Objective Response- Objective Response Rate (ORR)
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.
Time frame: 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.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| NSCLC Avelumab + Axitinib | Percentage of Participants With Confirmed Objective Response- Objective Response Rate (ORR) | 31.7 Percentage of participants |
| UC Avelumab + Axitinib | Percentage of Participants With Confirmed Objective Response- Objective Response Rate (ORR) | 10.0 Percentage of participants |
Secondary
Cmax of Axitinib
Time frame: 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.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| NSCLC Avelumab + Axitinib | Cmax of Axitinib | Cycle 1 (Day 15) | 17.29 Microgram per milliliter | Geometric Coefficient of Variation 198 |
| NSCLC Avelumab + Axitinib | Cmax of Axitinib | Cycle 2 (Day 1) | 16.46 Microgram per milliliter | Geometric Coefficient of Variation 91 |
| NSCLC Avelumab + Axitinib | Cmax of Axitinib | Cycle 2 (Day15) | 10.64 Microgram per milliliter | Geometric Coefficient of Variation 223 |
| UC Avelumab + Axitinib | Cmax of Axitinib | Cycle 1 (Day 15) | 14.64 Microgram per milliliter | Geometric Coefficient of Variation 448 |
| UC Avelumab + Axitinib | Cmax of Axitinib | Cycle 2 (Day 1) | 5.206 Microgram per milliliter | Geometric Coefficient of Variation 448 |
| UC Avelumab + Axitinib | Cmax of Axitinib | Cycle 2 (Day15) | 2.868 Microgram per milliliter | Geometric Coefficient of Variation 24 |
Secondary
Ctrough of Axitinib
Time frame: Pre-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.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| NSCLC Avelumab + Axitinib | Ctrough of Axitinib | Cycle 1 (Day 15) | 7.923 Microgram per milliliter | Geometric Coefficient of Variation 127 |
| NSCLC Avelumab + Axitinib | Ctrough of Axitinib | Cycle 2 (Day 1) | 8.871 Microgram per milliliter | Geometric Coefficient of Variation 123 |
| NSCLC Avelumab + Axitinib | Ctrough of Axitinib | Cycle 2 (Day 15) | 6.455 Microgram per milliliter | Geometric Coefficient of Variation 129 |
| UC Avelumab + Axitinib | Ctrough of Axitinib | Cycle 1 (Day 15) | 4.613 Microgram per milliliter | Geometric Coefficient of Variation 231 |
| UC Avelumab + Axitinib | Ctrough of Axitinib | Cycle 2 (Day 1) | 5.247 Microgram per milliliter | Geometric Coefficient of Variation 172 |
| UC Avelumab + Axitinib | Ctrough of Axitinib | Cycle 2 (Day 15) | 3.944 Microgram per milliliter | Geometric Coefficient of Variation 172 |
Secondary
Duration of Response in Participants With Confirmed CR or PR
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.
Time frame: 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.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| NSCLC Avelumab + Axitinib | Duration of Response in Participants With Confirmed CR or PR | 7.5 Months |
| UC Avelumab + Axitinib | Duration of Response in Participants With Confirmed CR or PR | 17.4 Months |
Secondary
Maximum Observed Serum Concentration (Cmax) of Avelumab
Time frame: 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.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| NSCLC Avelumab + Axitinib | Maximum Observed Serum Concentration (Cmax) of Avelumab | Cycle 1 (Day 1) | 235.0 Microgram per milliliter | Geometric Coefficient of Variation 26 |
| NSCLC Avelumab + Axitinib | Maximum Observed Serum Concentration (Cmax) of Avelumab | Cycle 1 (Day 15) | 264.0 Microgram per milliliter | Geometric Coefficient of Variation 34 |
| NSCLC Avelumab + Axitinib | Maximum Observed Serum Concentration (Cmax) of Avelumab | Cycle 2 (Day 1) | 283.2 Microgram per milliliter | Geometric Coefficient of Variation 24 |
| UC Avelumab + Axitinib | Maximum Observed Serum Concentration (Cmax) of Avelumab | Cycle 1 (Day 1) | 206.3 Microgram per milliliter | Geometric Coefficient of Variation 27 |
| UC Avelumab + Axitinib | Maximum Observed Serum Concentration (Cmax) of Avelumab | Cycle 1 (Day 15) | 163.9 Microgram per milliliter | Geometric Coefficient of Variation 211 |
| UC Avelumab + Axitinib | Maximum Observed Serum Concentration (Cmax) of Avelumab | Cycle 2 (Day 1) | 260.4 Microgram per milliliter | Geometric Coefficient of Variation 25 |
Secondary
Number of Participants With Positive Anti-drug Antibody (ADA) and Neutralizing Antibodies (nAb) Against Avelumab
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.
Time frame: 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.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| NSCLC Avelumab + Axitinib | Number of Participants With Positive Anti-drug Antibody (ADA) and Neutralizing Antibodies (nAb) Against Avelumab | ADA ever-Positive | 7 Participants |
| UC Avelumab + Axitinib | Number of Participants With Positive Anti-drug Antibody (ADA) and Neutralizing Antibodies (nAb) Against Avelumab | ADA ever-Positive | 0 Participants |
Secondary
Number of Participants With Programmed Death-Ligand 1 (PD-L1) Status
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.
Time frame: 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.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| NSCLC Avelumab + Axitinib | Number of Participants With Programmed Death-Ligand 1 (PD-L1) Status | PD-L1 positive | 8 Participants |
| NSCLC Avelumab + Axitinib | Number of Participants With Programmed Death-Ligand 1 (PD-L1) Status | PD-L1 negative | 24 Participants |
| UC Avelumab + Axitinib | Number of Participants With Programmed Death-Ligand 1 (PD-L1) Status | PD-L1 positive | 5 Participants |
| UC Avelumab + Axitinib | Number of Participants With Programmed Death-Ligand 1 (PD-L1) Status | PD-L1 negative | 11 Participants |
Secondary
Overall Survival
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.
Time frame: 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.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| NSCLC Avelumab + Axitinib | Overall Survival | 15.4 Months |
| UC Avelumab + Axitinib | Overall Survival | 16.8 Months |
Secondary
Percentage of Participants With Chemistry Test Results of Maximum CTCAE Grade During the On-Treatment Period
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.
Time frame: 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. 'Number Analyzed' signifies number of participants evaluable for the specified rows.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| NSCLC Avelumab + Axitinib | 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 |
| NSCLC Avelumab + Axitinib | 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 |
| NSCLC Avelumab + Axitinib | 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 |
| NSCLC Avelumab + Axitinib | 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 |
| NSCLC Avelumab + Axitinib | 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 |
| NSCLC Avelumab + Axitinib | 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 |
| NSCLC Avelumab + Axitinib | Percentage of Participants With Chemistry Test Results of Maximum CTCAE Grade During the On-Treatment Period | Hyperglycemia (Grade 3) | 4.9 Percentage of participants |
| NSCLC Avelumab + Axitinib | Percentage of Participants With Chemistry Test Results of Maximum CTCAE Grade During the On-Treatment Period | Hyperglycemia (Grade 4) | 2.4 Percentage of participants |
| NSCLC Avelumab + Axitinib | Percentage of Participants With Chemistry Test Results of Maximum CTCAE Grade During the On-Treatment Period | Hyperkalemia (Grade 3) | 7.3 Percentage of participants |
| NSCLC Avelumab + Axitinib | Percentage of Participants With Chemistry Test Results of Maximum CTCAE Grade During the On-Treatment Period | Hypermagnesemia (Grade 3) | 2.4 Percentage of participants |
| NSCLC Avelumab + Axitinib | Percentage of Participants With Chemistry Test Results of Maximum CTCAE Grade During the On-Treatment Period | Hypermagnesemia (Grade 4) | 0 Percentage of participants |
| NSCLC Avelumab + Axitinib | Percentage of Participants With Chemistry Test Results of Maximum CTCAE Grade During the On-Treatment Period | Hypoalbuminemia (Grade 3) | 0 Percentage of participants |
| NSCLC Avelumab + Axitinib | Percentage of Participants With Chemistry Test Results of Maximum CTCAE Grade During the On-Treatment Period | Hypocalcemia (Grade 3) | 4.9 Percentage of participants |
| NSCLC Avelumab + Axitinib | Percentage of Participants With Chemistry Test Results of Maximum CTCAE Grade During the On-Treatment Period | Hypoglycemia (Grade 4) | 2.4 Percentage of participants |
| NSCLC Avelumab + Axitinib | Percentage of Participants With Chemistry Test Results of Maximum CTCAE Grade During the On-Treatment Period | Hypokalemia (Grade 3) | 4.9 Percentage of participants |
| NSCLC Avelumab + Axitinib | Percentage of Participants With Chemistry Test Results of Maximum CTCAE Grade During the On-Treatment Period | Hypomagnesemia (Grade 3) | 2.4 Percentage of participants |
| NSCLC Avelumab + Axitinib | Percentage of Participants With Chemistry Test Results of Maximum CTCAE Grade During the On-Treatment Period | Hypomagnesemia (Grade 4) | 2.4 Percentage of participants |
| NSCLC Avelumab + Axitinib | Percentage of Participants With Chemistry Test Results of Maximum CTCAE Grade During the On-Treatment Period | Hyponatremia (Grade 3) | 9.8 Percentage of participants |
| NSCLC Avelumab + Axitinib | Percentage of Participants With Chemistry Test Results of Maximum CTCAE Grade During the On-Treatment Period | Hyponatremia (Grade 4) | 2.4 Percentage of participants |
| NSCLC Avelumab + Axitinib | Percentage of Participants With Chemistry Test Results of Maximum CTCAE Grade During the On-Treatment Period | Hypophosphatemia (Grade 3) | 4.9 Percentage of participants |
| NSCLC Avelumab + Axitinib | 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 |
| NSCLC Avelumab + Axitinib | 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 |
| NSCLC Avelumab + Axitinib | 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 |
| UC Avelumab + Axitinib | Percentage of Participants With Chemistry Test Results of Maximum CTCAE Grade During the On-Treatment Period | Hypoalbuminemia (Grade 3) | 5.6 Percentage of participants |
| UC Avelumab + Axitinib | Percentage of Participants With Chemistry Test Results of Maximum CTCAE Grade During the On-Treatment Period | Alanine aminotransferase increased (Grade 3) | 5.6 Percentage of participants |
| UC Avelumab + Axitinib | Percentage of Participants With Chemistry Test Results of Maximum CTCAE Grade During the On-Treatment Period | Hyponatremia (Grade 3) | 16.7 Percentage of participants |
| UC Avelumab + Axitinib | Percentage of Participants With Chemistry Test Results of Maximum CTCAE Grade During the On-Treatment Period | Alkaline phosphatase increased (Grade 3) | 11.1 Percentage of participants |
| UC Avelumab + Axitinib | Percentage of Participants With Chemistry Test Results of Maximum CTCAE Grade During the On-Treatment Period | Hypocalcemia (Grade 3) | 5.6 Percentage of participants |
| UC Avelumab + Axitinib | Percentage of Participants With Chemistry Test Results of Maximum CTCAE Grade During the On-Treatment Period | Aspartate aminotransferase increased (Grade 3) | 5.6 Percentage of participants |
| UC Avelumab + Axitinib | Percentage of Participants With Chemistry Test Results of Maximum CTCAE Grade During the On-Treatment Period | Lipase increased (Grade 3) | 6.3 Percentage of participants |
| UC Avelumab + Axitinib | Percentage of Participants With Chemistry Test Results of Maximum CTCAE Grade During the On-Treatment Period | Blood bilirubin increased (Grade 3) | 0 Percentage of participants |
| UC Avelumab + Axitinib | Percentage of Participants With Chemistry Test Results of Maximum CTCAE Grade During the On-Treatment Period | Hypoglycemia (Grade 4) | 0 Percentage of participants |
| UC Avelumab + Axitinib | Percentage of Participants With Chemistry Test Results of Maximum CTCAE Grade During the On-Treatment Period | Creatinine increased (Grade 3) | 5.6 Percentage of participants |
| UC Avelumab + Axitinib | Percentage of Participants With Chemistry Test Results of Maximum CTCAE Grade During the On-Treatment Period | Hyponatremia (Grade 4) | 0 Percentage of participants |
| UC Avelumab + Axitinib | Percentage of Participants With Chemistry Test Results of Maximum CTCAE Grade During the On-Treatment Period | GGT increased (Grade 3) | 18.8 Percentage of participants |
| UC Avelumab + Axitinib | Percentage of Participants With Chemistry Test Results of Maximum CTCAE Grade During the On-Treatment Period | Hypokalemia (Grade 3) | 0 Percentage of participants |
| UC Avelumab + Axitinib | Percentage of Participants With Chemistry Test Results of Maximum CTCAE Grade During the On-Treatment Period | Hyperglycemia (Grade 3) | 5.6 Percentage of participants |
| UC Avelumab + Axitinib | Percentage of Participants With Chemistry Test Results of Maximum CTCAE Grade During the On-Treatment Period | Serum amylase increase (Grade 3) | 12.5 Percentage of participants |
| UC Avelumab + Axitinib | Percentage of Participants With Chemistry Test Results of Maximum CTCAE Grade During the On-Treatment Period | Hyperglycemia (Grade 4) | 0 Percentage of participants |
| UC Avelumab + Axitinib | Percentage of Participants With Chemistry Test Results of Maximum CTCAE Grade During the On-Treatment Period | Hypomagnesemia (Grade 3) | 0 Percentage of participants |
| UC Avelumab + Axitinib | Percentage of Participants With Chemistry Test Results of Maximum CTCAE Grade During the On-Treatment Period | Hyperkalemia (Grade 3) | 0 Percentage of participants |
| UC Avelumab + Axitinib | Percentage of Participants With Chemistry Test Results of Maximum CTCAE Grade During the On-Treatment Period | Hypophosphatemia (Grade 3) | 5.6 Percentage of participants |
| UC Avelumab + Axitinib | Percentage of Participants With Chemistry Test Results of Maximum CTCAE Grade During the On-Treatment Period | Hypermagnesemia (Grade 3) | 0 Percentage of participants |
| UC Avelumab + Axitinib | Percentage of Participants With Chemistry Test Results of Maximum CTCAE Grade During the On-Treatment Period | Hypomagnesemia (Grade 4) | 0 Percentage of participants |
| UC Avelumab + Axitinib | Percentage of Participants With Chemistry Test Results of Maximum CTCAE Grade During the On-Treatment Period | Hypermagnesemia (Grade 4) | 5.6 Percentage of participants |
| UC Avelumab + Axitinib | Percentage of Participants With Chemistry Test Results of Maximum CTCAE Grade During the On-Treatment Period | Lipase increased (Grade 4) | 6.3 Percentage of participants |
Secondary
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
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.
Time frame: 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.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| NSCLC Avelumab + Axitinib | 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 |
| NSCLC Avelumab + Axitinib | 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 |
| NSCLC Avelumab + Axitinib | 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 |
| NSCLC Avelumab + Axitinib | 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 |
| UC Avelumab + Axitinib | 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) | 0 Percentage of participants |
| UC Avelumab + Axitinib | 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) | 5.6 Percentage of participants |
| UC Avelumab + Axitinib | 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) | 5.6 Percentage of participants |
| UC Avelumab + Axitinib | 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) | 0 Percentage of participants |
Secondary
Percentage of Participants With Treatment Emergent Adverse Events (TEAEs) During the On-Treatment Period
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).
Time frame: 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.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| NSCLC Avelumab + Axitinib | Percentage of Participants With Treatment Emergent Adverse Events (TEAEs) During the On-Treatment Period | 100.0 Percentage of Participants |
| UC Avelumab + Axitinib | Percentage of Participants With Treatment Emergent Adverse Events (TEAEs) During the On-Treatment Period | 100.0 Percentage of Participants |
Secondary
Pre-dose Observed Serum Concentration (Ctrough) of Avelumab
Time frame: 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
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.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| NSCLC Avelumab + Axitinib | Pre-dose Observed Serum Concentration (Ctrough) of Avelumab | Cycle 2 (Day 1) | 20.96 Microgram per milliliter | Geometric Coefficient of Variation 119 |
| NSCLC Avelumab + Axitinib | Pre-dose Observed Serum Concentration (Ctrough) of Avelumab | Cycle 6 (Day 15) | 29.68 Microgram per milliliter | Geometric Coefficient of Variation 52 |
| NSCLC Avelumab + Axitinib | Pre-dose Observed Serum Concentration (Ctrough) of Avelumab | Cycle 1 (Day 15) | 19.46 Microgram per milliliter | Geometric Coefficient of Variation 80 |
| NSCLC Avelumab + Axitinib | Pre-dose Observed Serum Concentration (Ctrough) of Avelumab | Cycle 9 (Day 15) | 32.84 Microgram per milliliter | Geometric Coefficient of Variation 29 |
| NSCLC Avelumab + Axitinib | Pre-dose Observed Serum Concentration (Ctrough) of Avelumab | Cycle 3 (Day 15) | 28.22 Microgram per milliliter | Geometric Coefficient of Variation 55 |
| NSCLC Avelumab + Axitinib | Pre-dose Observed Serum Concentration (Ctrough) of Avelumab | Cycle 12 (Day 15) | 36.71 Microgram per milliliter | Geometric Coefficient of Variation 50 |
| NSCLC Avelumab + Axitinib | Pre-dose Observed Serum Concentration (Ctrough) of Avelumab | Cycle 1 (Day 1) | 0 Microgram per milliliter | Geometric Coefficient of Variation 0 |
| UC Avelumab + Axitinib | Pre-dose Observed Serum Concentration (Ctrough) of Avelumab | Cycle 12 (Day 15) | 39.01 Microgram per milliliter | Geometric Coefficient of Variation 20 |
| UC Avelumab + Axitinib | Pre-dose Observed Serum Concentration (Ctrough) of Avelumab | Cycle 1 (Day 1) | 0 Microgram per milliliter | Geometric Coefficient of Variation 0 |
| UC Avelumab + Axitinib | Pre-dose Observed Serum Concentration (Ctrough) of Avelumab | Cycle 1 (Day 15) | 18.84 Microgram per milliliter | Geometric Coefficient of Variation 101 |
| UC Avelumab + Axitinib | Pre-dose Observed Serum Concentration (Ctrough) of Avelumab | Cycle 2 (Day 1) | 19.62 Microgram per milliliter | Geometric Coefficient of Variation 91 |
| UC Avelumab + Axitinib | Pre-dose Observed Serum Concentration (Ctrough) of Avelumab | Cycle 3 (Day 15) | 39.29 Microgram per milliliter | Geometric Coefficient of Variation 36 |
| UC Avelumab + Axitinib | Pre-dose Observed Serum Concentration (Ctrough) of Avelumab | Cycle 6 (Day 15) | 43.30 Microgram per milliliter | Geometric Coefficient of Variation 57 |
| UC Avelumab + Axitinib | Pre-dose Observed Serum Concentration (Ctrough) of Avelumab | Cycle 9 (Day 15) | 42.41 Microgram per milliliter | Geometric Coefficient of Variation 47 |
Secondary
Progression Free Survival (PFS)
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.
Time frame: 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.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| NSCLC Avelumab + Axitinib | Progression Free Survival (PFS) | 5.5 Months |
| UC Avelumab + Axitinib | Progression Free Survival (PFS) | 2.3 Months |
Secondary
T-cell Receptor (TCR) Sequencing to Identify Fraction Productive of Cells
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).
Time frame: 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.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| NSCLC Avelumab + Axitinib | T-cell Receptor (TCR) Sequencing to Identify Fraction Productive of Cells | 0.2 Proportion of T cells | Standard Deviation 0.17 |
| UC Avelumab + Axitinib | T-cell Receptor (TCR) Sequencing to Identify Fraction Productive of Cells | 0.1 Proportion of T cells | Standard Deviation 0.08 |
Secondary
T-cell Receptor (TCR) Sequencing to Identify Simpson Clonality
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.
Time frame: Pre-dose on Day 1 of Cycle 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.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| NSCLC Avelumab + Axitinib | T-cell Receptor (TCR) Sequencing to Identify Simpson Clonality | 0.1 Index | Standard Deviation 0.04 |
| UC Avelumab + Axitinib | T-cell Receptor (TCR) Sequencing to Identify Simpson Clonality | 0.1 Index | Standard Deviation 0.03 |
Secondary
T-cell Receptor (TCR) Sequencing to Identify Total T Cells
The immune response was measured by total TCR sequencing in peripheral blood and determined the characterization of immune repertoires.
Time frame: Pre-dose on Day 1 of Cycle 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.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| NSCLC Avelumab + Axitinib | T-cell Receptor (TCR) Sequencing to Identify Total T Cells | 1623.7 Cells | Standard Deviation 1971.39 |
| UC Avelumab + Axitinib | T-cell Receptor (TCR) Sequencing to Identify Total T Cells | 1168.4 Cells | Standard Deviation 1450.51 |
Secondary
Time to Tumor Response (TTR) in Participants With Confirmed CR or PR
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.
Time frame: 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.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| NSCLC Avelumab + Axitinib | Time to Tumor Response (TTR) in Participants With Confirmed CR or PR | 1.9 Months |
| UC Avelumab + Axitinib | Time to Tumor Response (TTR) in Participants With Confirmed CR or PR | 2.8 Months |
Secondary
Tumour Mutational Burden (TMB) in Tumor Tissue
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.
Time frame: 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.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| NSCLC Avelumab + Axitinib | Tumour Mutational Burden (TMB) in Tumor Tissue | 2.8 Mutations per megabase | Standard Deviation 2.97 |
| UC Avelumab + Axitinib | Tumour Mutational Burden (TMB) in Tumor Tissue | 3.7 Mutations per megabase | Standard Deviation 4.53 |