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

Sponsor

Pfizer (Industry)

Overall Status

Active, not recruiting

CT.gov ID

NCT03472560

Collaborator

(none)

Enrollment

Locations

Arm

55.9

Anticipated Duration (Months)

1.6

Patients Per Site

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Non-Small Cell Lung Cancer Urothelial Cancer	Drug: Avelumab (MSB0010718C) Drug: Axitinib (AG-013736)	Phase 2

Study Design

Study Type:

Interventional

Actual Enrollment :

60 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

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

Actual Study Start Date :

May 2, 2018

Anticipated Primary Completion Date :

Dec 28, 2022

Anticipated Study Completion Date :

Dec 28, 2022

Arms and Interventions

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

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

Outcome Measures

Primary Outcome Measures

Confirmed objective response [Baseline up to approximately 42 months]
Objective response (OR) is defined as a confirmed complete response (CR) or partial (PR) per RECIST v 1.1

Secondary Outcome Measures

Time to Tumor Response (TTR) [Baseline up to approximately 42 months]
Time to Tumor Response (TTR) is defined as the time from the date of first dose of study treatment to the first documentation of objective response [complete response (CR) or partial response (PR)].
Tumor tissue biomarker status (ie, positive or negative based on, for example, PD L1 expression and/or quantitation of tumor mutational burden as well as characterization of the immune repertoire in peripheral blood and/or tumor) [Screening and optional tumor biopsies obtained upon disease progression. Baseline up to approximately 42 months.]
Archived tumor tissue samples and de novo biopsies of primary and/or metastatic lesions. Tumor tissue biomarker status (ie, positive or negative based on, for example, PD L1 expression and/or quantitation of tumor mutational burden as well as characterization of the immune repertoire in peripheral blood and/or tumor).
Anti-drug antibody (ADA) titers against avelumab [Pre dose on Cycle 1 Day 1 and Day 15, Cycle 2 Day 1, and Day 15 of Cycles 3, 6, 9 and 12 (each cycle is 28 days)]
Immunogenicity assessment of avelumab.
Duration of Response (DR) [Baseline up to approximately 42 months]
Duration of Response (DR), is defined as the time from the first documentation of objective response [complete response (CR) or partial response (PR)] to the date of first documentation of progressive disease (PD) or death due to any cause, whichever occurs first.
Progression Free Survival (PFS) [Baseline up to approximately 42 months]
Progression Free Survival (PFS) is defined as the time from the date of first dose of study treatment to the date of the first documentation of progressive disease (PD) or death due to any cause, whichever occurs first.
Maximum Observed Plasma Concentration (Cmax) of axitinib [2-4 hours post dose Cycle 1 Day 15 and Cycle 2 Day 1 and Day 15 (each cycle is 28 days)]
Cmax defined as the maximum plasma concentration of axitinib
Predose Concentration (Ctrough) of avelumab [Pre dose Cycle 1 Day 1 and Day 15, Cycle 2 Day 1 and Day 15 of Cycles 3, 6, 9, and 12 (each cycle is 28 days)]
Ctrough is defined as the concentration at the end of avelumab dosage interval
Predose concentration (Ctrough) of axitinib [Pre dose Cycle 1 Day 15 and Cycle 2 Day 1 and Day 15 (each cycle is 28 days) take up to 2 hr prior to the start of infusion.]
Ctrough is defined as the concentration at the end of axitinib dosage interval
Neutralizing antibodies (nAb) against avelumab [Pre dose on Cycle 1 Day 1 and Day 15, Cycle 2 Day 1, and Day 15 of Cycles 3, 6, 9 and 12 (each cycle is 28 days)]
Immunogenicity assessment of avelumab.
Maximum Observed Plasma Concentration (Cmax) of avelumab [Post dose Cycle 1 Day 1 and Day 15, Cycle 2 Day 1 (each cycle is 28 days)]
Cmax defined as the maximum plasma concentration of avelumab
Overall Survival (OS) [Baseline up to approximately 42 months]
Overall Survival (OS) is defined as the time from the date of first dose of study treatment to the date of death due to any cause.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Arizona Oncology Associates- Saguaro Cancer Center	Glendale	Arizona	United States	85308
2	Arizona Oncology Associates- Biltmore Cancer Center	Phoenix	Arizona	United States	85016
3	Arizona Oncology Associates- Deer Valley Cancer Center	Phoenix	Arizona	United States	85027
4	Arizona Oncology Associates- East Valley Cancer Center	Tempe	Arizona	United States	85281
5	The Oncology Institute of Hope and Innovation	Glendale	California	United States	91204
6	The Oncology Institute of Hope and Innovation	Long Beach	California	United States	90805
7	The Oncology Institute of Hope and Innovation	Santa Ana	California	United States	92705
8	The Oncology Institute of Hope and Innovation	Whittier	California	United States	90602
9	Oncology Hematology Associates	Springfield	Missouri	United States	65807
10	Oncology Hematology West, PC dba Nebraska Cancer Specialists	Omaha	Nebraska	United States	68114
11	Oncology Hematology West, PC dba Nebraska Cancer Specialists	Omaha	Nebraska	United States	68130
12	Saint Francis Hospital	Greenville	South Carolina	United States	29601
13	Saint Francis Hospital Cancer Center	Greenville	South Carolina	United States	29607
14	Bacs-Kiskun Megyei Korhaz Onkoradiologiai Kozpont	Kecskemet		Hungary	H-6000
15	Pecsi Tudomanyegyetem Klinikai Kozpont	Pecs		Hungary	H-7624
16	Tudogyogyintezet Torokbalint	Torokbalint		Hungary	H-2045
17	Azienda Ospedaliero Universitaria Policlinico Umberto I	Roma		Italy	00161
18	Cardiologia - Azienda Ospedaliero Universitaria Policlinico Umberto I	Roma		Italy	00161
19	Farmacia Azienda Ospedaliero Universitaria Policlinico Umberto I	Roma		Italy	00161
20	UOC di Radiologia - Azienda Ospedaliero Universitaria Policlinico Umberto I	Roma		Italy	00161
21	National Cancer Center	Goyang-si	Gyeonggi-do	Korea, Republic of	10408
22	Seoul National University Bundang Hospital	Seongnam-si	Gyeonggi-do	Korea, Republic of	13620
23	Samsung Medical Center	Gangnam-gu	Seoul	Korea, Republic of	06351
24	Asan Medical Center	Songpa-gu	Seoul	Korea, Republic of	05505
25	Severance Hospital, Yonsei University Health System	Seoul		Korea, Republic of	03722
26	Regionalny Szpital Specjalistyczny Im. Dr. Wladyslawa Bieganskiego w Grudziadzu	Grudziadz		Poland	86-300
27	Centrum Medyczne Dom Lekarski S.A.	Szczecin		Poland	70-784
28	Centrum Onkologii Instytut im. Marii Sklodowskiej-Curie w Warszawie	Warszawa		Poland	02-781
29	GBUZ of Stavropol Territory "Pyatigorsk Inter-regional Oncology Dispanser"	Pyatigorsk	Stavropol Territory	Russian Federation	357502
30	LLC "University clinic of headache"	Moscow		Russian Federation	109028
31	Limited Liability Company "VitaMed" (LLC "VitaMed")	Moscow		Russian Federation	121309
32	LLC "University Clinic of Headache"	Moscow		Russian Federation	121467
33	Limited Liability Company "VitaMed" (LLC "VitaMed")	Moscow		Russian Federation	129515
34	Instituto Catalan de Oncologia	Hospitalet de Llobregat	Barcelona	Spain	08908
35	Consorcio Hospitalario Provincial de Castellon	Castellon		Spain	12002
36	Chi Mei Hospital, Liouying	Tainan City	Liouying District	Taiwan	73657
37	National Cheng Kung University Hospital	Tainan		Taiwan	704