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

A PHASE 2, OPEN LABEL STUDY TO EVALUATE SAFETY AND CLINICAL ACTIVITY OF AVELUMAB (BAVENCIO (REGISTERED)) IN COMBINATION WITH AXITINIB (INLYTA (REGISTERED)) IN PATIENTS WITH ADVANCED OR METASTATIC PREVIOUSLY TREATED NON-SMALL CELL LUNG CANCER OR TREATMENT NAÏVE CISPLATIN-INELIGIBLE UROTHELIAL CANCER JAVELIN MEDLEY VEGF

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.

Study Overview

• Status: Terminated
• Conditions: Non-Small Cell Lung Cancer; Urothelial Cancer
• Intervention / Treatment: Drug: Avelumab (MSB0010718C); Drug: Axitinib (AG-013736)

• Study Type: Interventional
• Enrollment (Actual): 61
• Phase: Phase 2

Contacts and Locations

Study Locations

• Hungary
  • Kecskemet, Hungary, H-6000
    • Bacs-Kiskun Megyei Korhaz Onkoradiologiai Kozpont
  • Pecs, Hungary, H-7624
    • Pecsi Tudomanyegyetem Klinikai Kozpont
  • Torokbalint, Hungary, H-2045
    • Tudogyogyintezet Torokbalint
• Italy
  • Roma, Italy, 00161
    • Azienda Ospedaliero Universitaria Policlinico Umberto I
  • Roma, Italy, 00161
    • Cardiologia - Azienda Ospedaliero Universitaria Policlinico Umberto I
  • Roma, Italy, 00161
    • Farmacia Azienda Ospedaliero Universitaria Policlinico Umberto I
  • Roma, Italy, 00161
    • UOC di Radiologia - Azienda Ospedaliero Universitaria Policlinico Umberto I
• Korea, Republic of
  • Seoul, Korea, Republic of, 03722
    • Severance Hospital, Yonsei University Health System
  • Gyeonggi-do
    • Goyang-si, Gyeonggi-do, Korea, Republic of, 10408
      • National Cancer Center
    • Seongnam-si, Gyeonggi-do, Korea, Republic of, 13620
      • Seoul National University Bundang Hospital
  • Seoul
    • Gangnam-gu, Seoul, Korea, Republic of, 06351
      • Samsung Medical Center
    • Songpa-gu, Seoul, Korea, Republic of, 05505
      • Asan Medical Center
• Poland
  • Grudziadz, Poland, 86-300
    • Regionalny Szpital Specjalistyczny Im. Dr. Wladyslawa Bieganskiego w Grudziadzu
  • Szczecin, Poland, 70-784
    • Centrum Medyczne Dom Lekarski S.A.
  • Warszawa, Poland, 02-781
    • Centrum Onkologii Instytut im. Marii Sklodowskiej-Curie w Warszawie
  • Mazowieckie
    • Warszawa, Mazowieckie, Poland, 02-781
      • Narodowy Instytut Onkologii im. Marii Sklodowskiej-Curie - Panstwowy Instytut Badawczy w Warszawie
• Russian Federation
  • Moscow, Russian Federation, 121309
    • Limited Liability Company "VitaMed" (LLC "VitaMed")
  • Moscow, Russian Federation, 109028
    • LLC "University Clinic of Headache"
  • Moscow, Russian Federation, 121467
    • LLC "University Clinic of Headache"
  • Moscow, Russian Federation, 129515
    • Limited Liability Company "VitaMed" (LLC "VitaMed")
  • Stavropol Territory
    • Pyatigorsk, Stavropol Territory, Russian Federation, 357502
      • GBUZ of Stavropol Territory "Pyatigorsk Inter-regional Oncology Dispanser"
• Spain
  • Castellon, Spain, 12002
    • Consorcio Hospitalario Provincial de Castellon
  • Barcelona
    • Hospitalet de Llobregat, Barcelona, Spain, 08908
      • Instituto Catalán de Oncología
• Taiwan
  • Tainan, Taiwan, 704
    • National Cheng Kung University Hospital
  • Liouying District
    • Tainan City, Liouying District, Taiwan, 73657
      • Chi Mei Hospital, Liouying
• United States
  • Arizona
    • Glendale, Arizona, United States, 85308
      • Arizona Oncology Associates- Saguaro Cancer Center
    • Goodyear, Arizona, United States, 85395
      • Arizona Oncology Associates
    • Phoenix, Arizona, United States, 85016
      • Arizona Oncology Associates- Biltmore Cancer Center
    • Phoenix, Arizona, United States, 85027
      • Arizona Oncology Associates- Deer Valley Cancer Center
    • Tempe, Arizona, United States, 85281
      • Arizona Oncology Associates- East Valley Cancer Center
  • California
    • Glendale, California, United States, 91204
      • The Oncology Institute of Hope and Innovation
    • Long Beach, California, United States, 90805
      • The Oncology Institute of Hope and Innovation
    • Santa Ana, California, United States, 92705
      • The Oncology Institute of Hope and Innovation
    • Whittier, California, United States, 90602
      • The Oncology Institute of Hope and Innovation
  • Missouri
    • Springfield, Missouri, United States, 65807
      • Oncology Hematology Associates
  • Nebraska
    • Omaha, Nebraska, United States, 68130
      • Oncology Hematology West, PC dba Nebraska Cancer Specialists
    • Omaha, Nebraska, United States, 68114
      • Oncology Hematology West, PC dba Nebraska Cancer Specialists
  • South Carolina
    • Greenville, South Carolina, United States, 29601
      • Saint Francis Hospital
    • Greenville, South Carolina, United States, 29607
      • Saint Francis Hospital Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Avelumab in combination with axitinib; Avelumab administered at 800 mg IV every two weeks in combination with axitinib, 5 mg PO BID.	Drug: Avelumab (MSB0010718C); IV treatment: Avelumab administered at 800 mg IV every two weeks; Other Names: Bavencio; Drug: Axitinib (AG-013736); Oral treatment: Axitinib given 5 mg PO BID; Other Names: Inlyta

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	Baseline up to 56 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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).	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)
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.	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)
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.	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)
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.	From date of start of treatment until date of first documentation of objective tumor response (maximum up to 56 months)
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.	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)
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.	From start of study treatment until first documentation of PD or death due to any cause or censoring date (maximum of 24 months)
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.	From date of start of study treatment until date of death or censoring date (maximum up to 56 months)
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
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
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	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.	Screening, up to 28 days prior to Day 1
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.	Screening, up to 28 days prior to Day 1
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).	Screening, up to 28 days prior to Day 1
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.	Pre-dose on Day 1 of Cycle 1
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.	Pre-dose on Day 1 of Cycle 1
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.	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)

Collaborators and Investigators

• Sponsor: Pfizer
• Investigators: Study Director: Pfizer CT.gov Call Center, Pfizer

Publications and helpful links

Helpful Links

• To obtain contact information for a study center near you, click here.

Study record dates

Study Major Dates

• Study Start (Actual): May 2, 2018
• Primary Completion (Actual): February 9, 2023
• Study Completion (Actual): February 9, 2023

Study Registration Dates

• First Submitted: February 28, 2018
• First Submitted That Met QC Criteria: March 20, 2018
• First Posted (Actual): March 21, 2018

Study Record Updates

• Last Update Posted (Actual): April 9, 2024
• Last Update Submitted That Met QC Criteria: March 12, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Keywords: Cancer; NSCLC; lung cancer; non-small cell lung cancer; Avelumab; bladder cancer; urothelial cancer; non small cell lung cancer; Axitinib; Bavencio; Inlyta
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Neoplasms; Lung Diseases; Neoplasms by Site; Respiratory Tract Neoplasms; Thoracic Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Carcinoma, Non-Small-Cell Lung; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Antineoplastic Agents, Immunological; Protein Kinase Inhibitors; Avelumab; Axitinib
• Other Study ID Numbers: B9991027; 2017-004345-24 (EudraCT Number); AVE/ AXI COMBO UC (Other Identifier: Alias Study Number); AVE/AXI COMBO UC/NSCLC (Other Identifier: Alias Study Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Pfizer will provide access to individual de-identified participant data and related study documents (e.g. protocol, Statistical Analysis Plan (SAP), Clinical Study Report (CSR)) upon request from qualified researchers, and subject to certain criteria, conditions, and exceptions. Further details on Pfizer's data sharing criteria and process for requesting access can be found at: https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No