Clinical trial NCT03472560: A Study of Avelumab in Combination With Axitinib In Non-Small Cell Lung Cancer (NSCLC) or Urothelial Cancer (Javelin Medley VEGF)
Official title: 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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Non-Small Cell Lung Cancer
Urothelial Cancer
Keywords: Cancer
non-small cell lung cancer
non small cell lung cancer
NSCLC
lung cancer
urothelial cancer
bladder cancer
Avelumab
Bavencio
Axitinib
Inlyta
Lead sponsor: Pfizer
Sponsor class: INDUSTRY
First posted: 2018-03-21
Enrollment: 61
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


Eligibility criteria: 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.

Primary outcomes:
measure: Percentage of Participants With Confirmed Objective Response- Objective Response Rate (ORR)
timeFrame: Baseline up to 56 months
Secondary outcomes:
measure: Percentage of Participants With Treatment Emergent Adverse Events (TEAEs) During the On-Treatment Period
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)
measure: 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
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)
measure: Percentage of Participants With Chemistry Test Results of Maximum CTCAE Grade During the On-Treatment Period
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)
measure: Time to Tumor Response (TTR) in Participants With Confirmed CR or PR
timeFrame: From date of start of treatment until date of first documentation of objective tumor response (maximum up to 56 months)
measure: Duration of Response in Participants With Confirmed CR or PR
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)
measure: Progression Free Survival (PFS)
timeFrame: From start of study treatment until first documentation of PD or death due to any cause or censoring date (maximum of 24 months)
measure: Overall Survival
timeFrame: From date of start of study treatment until date of death or censoring date (maximum up to 56 months)
measure: Maximum Observed Serum Concentration (Cmax) of Avelumab
timeFrame: Pre-dose, 1 hour post-dose on Cycle 1 Day 1, Day 15 and Cycle 2 Day 1
measure: Cmax of Axitinib
timeFrame: Pre-dose, 2 hour post-dose on Cycle 1 Day 15, Cycle 2 Day 1 and 15
measure: Pre-dose Observed Serum Concentration (Ctrough) of Avelumab
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
measure: Ctrough of Axitinib
timeFrame: Pre-dose on Cycle 1 Day 15, Cycle 2 Day 1 and 15
measure: Number of Participants With Programmed Death-Ligand 1 (PD-L1) Status
timeFrame: Screening, up to 28 days prior to Day 1
measure: Tumour Mutational Burden (TMB) in Tumor Tissue
timeFrame: Screening, up to 28 days prior to Day 1
measure: T-cell Receptor (TCR) Sequencing to Identify Fraction Productive of Cells
timeFrame: Screening, up to 28 days prior to Day 1
measure: T-cell Receptor (TCR) Sequencing to Identify Simpson Clonality
timeFrame: Pre-dose on Day 1 of Cycle 1
measure: T-cell Receptor (TCR) Sequencing to Identify Total T Cells
timeFrame: Pre-dose on Day 1 of Cycle 1
measure: Number of Participants With Positive Anti-drug Antibody (ADA) and Neutralizing Antibodies (nAb) Against Avelumab
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)
Other outcomes:
Locations:
city: Glendale
country: United States
facility: Arizona Oncology Associates- Saguaro Cancer Center
state: Arizona
city: Goodyear
country: United States
facility: Arizona Oncology Associates
state: Arizona
city: Phoenix
country: United States
facility: Arizona Oncology Associates- Biltmore Cancer Center
state: Arizona
city: Phoenix
country: United States
facility: Arizona Oncology Associates- Deer Valley Cancer Center
state: Arizona
city: Tempe
country: United States
facility: Arizona Oncology Associates- East Valley Cancer Center
state: Arizona
city: Glendale
country: United States
facility: The Oncology Institute of Hope and Innovation
state: California
city: Long Beach
country: United States
facility: The Oncology Institute of Hope and Innovation
state: California
city: Santa Ana
country: United States
facility: The Oncology Institute of Hope and Innovation
state: California
city: Whittier
country: United States
facility: The Oncology Institute of Hope and Innovation
state: California
city: Springfield
country: United States
facility: Oncology Hematology Associates
state: Missouri
city: Omaha
country: United States
facility: Oncology Hematology West, PC dba Nebraska Cancer Specialists
state: Nebraska
city: Omaha
country: United States
facility: Oncology Hematology West, PC dba Nebraska Cancer Specialists
state: Nebraska
city: Greenville
country: United States
facility: Saint Francis Hospital
state: South Carolina
city: Greenville
country: United States
facility: Saint Francis Hospital Cancer Center
state: South Carolina
city: Kecskemet
country: Hungary
facility: Bacs-Kiskun Megyei Korhaz Onkoradiologiai Kozpont
city: Pecs
country: Hungary
facility: Pecsi Tudomanyegyetem Klinikai Kozpont
city: Torokbalint
country: Hungary
facility: Tudogyogyintezet Torokbalint
city: Roma
country: Italy
facility: Azienda Ospedaliero Universitaria Policlinico Umberto I
city: Roma
country: Italy
facility: Cardiologia - Azienda Ospedaliero Universitaria Policlinico Umberto I
city: Roma
country: Italy
facility: Farmacia Azienda Ospedaliero Universitaria Policlinico Umberto I
city: Roma
country: Italy
facility: UOC di Radiologia - Azienda Ospedaliero Universitaria Policlinico Umberto I
city: Goyang-si
country: Korea, Republic of
facility: National Cancer Center
state: Gyeonggi-do
city: Seongnam-si
country: Korea, Republic of
facility: Seoul National University Bundang Hospital
state: Gyeonggi-do
city: Gangnam-gu
country: Korea, Republic of
facility: Samsung Medical Center
state: Seoul
city: Songpa-gu
country: Korea, Republic of
facility: Asan Medical Center
state: Seoul
city: Seoul
country: Korea, Republic of
facility: Severance Hospital, Yonsei University Health System
city: Warszawa
country: Poland
facility: Narodowy Instytut Onkologii im. Marii Sklodowskiej-Curie - Panstwowy Instytut Badawczy w Warszawie
state: Mazowieckie
city: Grudziadz
country: Poland
facility: Regionalny Szpital Specjalistyczny Im. Dr. Wladyslawa Bieganskiego w Grudziadzu
city: Szczecin
country: Poland
facility: Centrum Medyczne Dom Lekarski S.A.
city: Warszawa
country: Poland
facility: Centrum Onkologii Instytut im. Marii Sklodowskiej-Curie w Warszawie
city: Pyatigorsk
country: Russian Federation
facility: GBUZ of Stavropol Territory "Pyatigorsk Inter-regional Oncology Dispanser"
state: Stavropol Territory
city: Moscow
country: Russian Federation
facility: LLC "University clinic of headache"
city: Moscow
country: Russian Federation
facility: Limited Liability Company "VitaMed" (LLC "VitaMed")
city: Moscow
country: Russian Federation
facility: LLC "University Clinic of Headache"
city: Moscow
country: Russian Federation
facility: Limited Liability Company "VitaMed" (LLC "VitaMed")
city: Hospitalet de Llobregat
country: Spain
facility: Instituto Catalan de Oncologia
state: Barcelona
city: Castellon
country: Spain
facility: Consorcio Hospitalario Provincial de Castellon
city: Tainan City
country: Taiwan
facility: Chi Mei Hospital, Liouying
state: Liouying District
city: Tainan
country: Taiwan
facility: National Cheng Kung University Hospital
Study officials:
affiliation: Pfizer
name: Pfizer CT.gov Call Center
role: STUDY_DIRECTOR
References: