A Study of Bempegaldesleukin (NKTR-214: BEMPEG) in Combination With Nivolumab Compared With the Investigator's Choice of a Tyrosine Kinase Inhibitor (TKI) Therapy (Either Sunitinib or Cabozantinib Monotherapy) for Advanced Metastatic Renal Cell Carcinoma (RCC)

Sponsor

Nektar Therapeutics (Industry)

Overall Status

Active, not recruiting

CT.gov ID

NCT03729245

Collaborator

Bristol-Myers Squibb (Industry)

623

Enrollment

109

Locations

Arms

65.4

Anticipated Duration (Months)

5.7

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The main purpose of this study is to compare the objective response rate (ORR) and overall survival (OS) of bempegaldesleukin (NKTR-214: BEMPEG) combined with nivolumab to that of tyrosine kinase inhibitor (TKI) monotherapy (sunitinib or cabozantinib) in IMDC intermediate- or poor-risk patients and IMDC all-risk patients with previously untreated advanced renal cell carcinoma (RCC).

Condition or Disease	Intervention/Treatment	Phase
Renal Cell Carcinoma Metastatic Renal Cell Carcinoma	Biological: bempegaldesleukin Drug: sunitinib Biological: nivolumab Drug: cabozantinib	Phase 3

Study Design

Study Type:

Interventional

Actual Enrollment :

623 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

A Phase 3 Randomized Open Label Study to Compare NKTR-214 Combined With Nivolumab to the Investigator's Choice of Sunitinib or Cabozantinib in Patients With Previously Untreated Advanced Renal Cell Carcinoma

Actual Study Start Date :

Dec 18, 2018

Anticipated Primary Completion Date :

Jun 1, 2022

Anticipated Study Completion Date :

Jun 1, 2024

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Combination of bempegaldesleukin + nivolumab Patients in Arm A will receive bempegaldesleukin in combination with nivolumab.	Biological: bempegaldesleukin Specified dose on specified days Other Names: BEMPEG BMS-986321 Biological: nivolumab Specified dose on specified days Other Names: Opdivo® BMS-936558
Active Comparator: sunitinib or cabozantinib Patients in Arm B will receive the Investigator's choice of either one of two treatment options.	Drug: sunitinib Specified dose on specified days Other Names: Sutent® Drug: cabozantinib Specified dose on specified days Other Names: Cabometyx®

Arm

Intervention/Treatment

Experimental: Combination of bempegaldesleukin + nivolumab

Patients in Arm A will receive bempegaldesleukin in combination with nivolumab.

Biological: bempegaldesleukin

Specified dose on specified days

Other Names:

BEMPEG

BMS-986321

Biological: nivolumab

Specified dose on specified days

Other Names:

Opdivo®

BMS-936558

Active Comparator: sunitinib or cabozantinib

Patients in Arm B will receive the Investigator's choice of either one of two treatment options.

Drug: sunitinib

Specified dose on specified days

Other Names:

Sutent®

Drug: cabozantinib

Specified dose on specified days

Other Names:

Cabometyx®

Outcome Measures

Primary Outcome Measures

ORR using mRECIST 1.1 by BICR in IMDC intermediate- or poor-risk patients with previously untreated advanced RCC [Approximately 32 months]
ORR using modified Response Evaluation Criteria in Solid Tumors (mRECIST) 1.1 by Blinded Independent Central Review (BICR) in International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) intermediate- or poor-risk patients. ORR is defined as the proportion of enrolled participants who achieved a Best Overall Response (BOR) of CR or PR. CR is defined as disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) had to have reduction in short axis to < 10 mm. PR is defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. ORR is calculated as the sum of CR and PR.
ORR per mRECIST 1.1 by BICR in IMDC all-risk patients with previously untreated advanced RCC [Approximately 32 months]
ORR is defined as the proportion of enrolled participants who achieved a Best Overall Response (BOR) of CR or PR. CR is defined as disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) had to have reduction in short axis to <10 mm. PR is defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. ORR is calculated as the sum of CR and PR.
Overall survival (OS) in IMDC intermediate- or poor-risk patients with previously untreated advanced RCC [32-59 months]
OS is defined as the time from date of first dose to the date of death.
OS in IMDC all-risk patients with previously untreated advanced RCC [32-59 months]
OS is defined as the time from date of first dose to the date of death.

Secondary Outcome Measures

Progression-free survival (PFS) per mRECIST 1.1 by BICR in IMDC intermediate- or poor-risk patients with previously untreated advanced RCC [32-59 months]
PFS is defined as the time from date of first dose to the date of the first objectively documented tumor progression or death due to any cause.
PFS per mRECIST 1.1 by BICR in IMDC all risk-patients with previously untreated advanced RCC [32-59 months]
PFS is defined as the time from date of first dose to the date of the first objectively documented tumor progression or death due to any cause.
Incidence of treatment-related Adverse Events (AEs) of Bempegaldesleukin combined with Nivolumab versus TKI monotherapy (sunitinib or cabozantinib) in patients with previously untreated advanced RCC [Up to 5 years]
Changes in cancer-related symptoms and quality-of-life in patients using the National Comprehensive Cancer Network/Functional Assessment of Cancer Therapy (NCCN/FACT) Symptom Index for Kidney Cancer (FKSI-19) [32-59 months]
Health outcome and quality of life as measured by NCCN/FACT FKSI-19 questionnaire. The FKSI-19 is a disease-specific instrument that measures disease and treatment-related symptoms specifically in renal cancer patients in 4 domains. The DRS-P domain assesses symptoms experienced in the past 7 days. Participants are asked to respond to 12 questions ("I have a lack of energy," "I feel pain," for example) by using a 5-point scale (0=not at all, 1=a little bit, 2=somewhat, 3=quite a bit, 4=very much; possible total domain score of 0 to 48). A negative change from baseline indicates a worsening of condition.
PD-L1 expression on tumor cells (< 1% vs ≥ 1%) using the PD-L1 immunohistochemistry (IHC) 28-8 pharmDx assay as a predictive biomarker for ORR, PFS, and OS in patients with previously untreated advanced RCC [32-59 months]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Key Inclusion Criteria:

Provide written, informed consent to participate in the study and follow the study procedures
Karnofsky Performance Status (KPS) of at least 70%
Measurable disease per mRECIST 1.1 criteria
Histologically confirmed RCC with a clear-cell component (may have sarcomatoid features); advanced (not amenable to curative surgery or radiation therapy) or metastatic (AJCC Stage IV) RCC
Patients with any International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) score (favorable-, intermediate-, or poor-risk) are eligible. At least one IMDC prognostic factor must be present to qualify as either intermediate- or poor-risk renal cell carcinoma.
No prior systemic therapy (including neoadjuvant, adjuvant, or vaccine therapy) for RCC

Key Exclusion Criteria:

An active, known or suspected autoimmune disease that has required systemic treatment within the past 3 months (exceptions exist)
Patients who have a known additional malignancy that is progressing or requires active treatment (exceptions exist)
Any tumor invading the wall of a major blood vessels
Any tumor invading the gastrointestinal (GI) tract or any evidence of endotracheal or endobronchial tumor within 28 days prior to randomization
Need for >2 medications for management of hypertension (including diuretics)
History of pulmonary embolism, deep vein thrombosis (not including tumor thrombus), or clinically significant thromboembolic event within 3 months of randomization

Additional protocol defined inclusion/exclusion criteria and exceptions apply

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Alaska Urological	Anchorage	Alaska	United States	99508
2	Southeastern Regional Medical Center - CTCA - PPDS	Goodyear	Arizona	United States	85338
3	CARTI Cancer Center	Little Rock	Arkansas	United States	72205
4	City of Hope National Medical Center	Duarte	California	United States	91010
5	Cedars Sinai Medical Center	Los Angeles	California	United States	90048
6	University of California Irvine	Orange	California	United States	92868
7	Innovative Clinical Research Institute, LLC	Whittier	California	United States	90603
8	University of Miami	Miami	Florida	United States	33136
9	Winship Cancer Institute, Emory University	Atlanta	Georgia	United States	30322
10	Tulane Medical Center	New Orleans	Louisiana	United States	70112
11	University of Maryland Greenebaum Cancer Center	Baltimore	Maryland	United States	21201
12	Comprehensive Cancer Centers of Nevada	Henderson	Nevada	United States	89052
13	North Shore Hematology Oncology Association PC	East Setauket	New York	United States	11733
14	Kettering Medical Center	Kettering	Ohio	United States	45429
15	Providence Cancer Institute, Franz Clinic	Portland	Oregon	United States	97213
16	Lehigh Valley Physician Group (LVPG) - Hematology Oncology	Allentown	Pennsylvania	United States	18103
17	Penn State Milton S Hershey Medical Center	Hershey	Pennsylvania	United States	17033
18	Thomas Jefferson University	Philadelphia	Pennsylvania	United States	19107
19	Eastern Regional Medical Center - CTCA	Philadelphia	Pennsylvania	United States	19124
20	Allegheny General Hospital	Pittsburgh	Pennsylvania	United States	15212
21	MD Anderson Cancer Center	Houston	Texas	United States	77030
22	Huntsman Cancer Hospital - PPDS	Salt Lake City	Utah	United States	84112
23	CAIPO Centro para la atención integral del paciente oncológico	San Miguel De Tucumán	Buenos Aires	Argentina	2700
24	Fundacion Koriza	Santa Rosa	La Pampa	Argentina	6300
25	Centro de Investigación Clínica - Clínica Viedma	Viedma	Rio Negro	Argentina	R8500ACE
26	Hospital Provincial Del Centenario	Rosario	Santa Fe	Argentina	S2000DSV
27	Hospital Provincial Del Centenario	Rosario	Santa Fe	Argentina	S2002KDS
28	Centro Médico Austral	Buenos Aires		Argentina	C1019ABS
29	Fundación Sanatorio Güemes	Buenos Aires		Argentina	C1180AAX
30	Instituto Médico Especializado Alexander Fleming	Buenos Aires		Argentina	C1426ANZ
31	Sanatorio Allende S.A.	Córdoba		Argentina	X5000JHQ
32	Sanatorio Allende S.A.	Córdoba		Argentina	X5002AOQ
33	Sanatorio Privado Duarte Quirós, de Clínica Colombo S.A.	Córdoba		Argentina	X5008HHW
34	Centro Oncologico Riojano Integral (cori)	La Rioja		Argentina	F5300COE
35	Centro Médico San Roque	San Miguel De Tucumán		Argentina	4000
36	Orange Cancer Centre	Orange	New South Wales	Australia	2800
37	Royal North Shore Hospital	Saint Leonards	New South Wales	Australia	2065
38	Macquarie University	Sydney	New South Wales	Australia	2109
39	Adelaide Cancer Centre	Kurralta Park	South Australia	Australia	5037
40	Barwon Health	Geelong	Victoria	Australia	3220
41	Centro de Oncologia Da Bahia	Salvador	Bahia	Brazil	41820-021
42	Centro de Oncologia Da Bahia	Salvador	Bahia	Brazil	41950-610
43	Cenantron - Centro Avancado de Tratamento Oncologico Ltda	Belo Horizonte	Minas Gerais	Brazil	30190-130
44	Oncocentro, Belo Horizonte	Belo Horizonte	Minas Gerais	Brazil	30190-130
45	Liga Paranaense de Combate Ao Cancer - Hospital Erasto Gaertner	Curitiba	Parana	Brazil	81520-060
46	Liga Norte Riograndense Contra O Cancer	Natal	Rio Grande Do Norte	Brazil	98700-000
47	Associação Hospital de Caridade Ijuí	Ijuí	Rio Grande Do Sul	Brazil	98700-000
48	Hospital Bruno Born	Lajeado	Rio Grande Do Sul	Brazil	95900-000
49	Universidade Federal do Rio Grande do Sul - UFRGS	Porto Alegre	Rio Grande Do Sul	Brazil	90035
50	Irmandade Da Santa Casa de Misericordia de Porto Alegre	Porto Alegre	Rio Grande Do Sul	Brazil	90050-170
51	Universidade Federal do Rio Grande do Sul - UFRGS	Porto Alegre	Rio Grande Do Sul	Brazil	90110-270
52	Hospital Sao Lucas Da Pontificia Universidade Catolica Do Rio Grande Do Sul (PUCRS)	Porto Alegre	Rio Grande Do Sul	Brazil	90610-000
53	Hospital Sao Lucas Da Pontificia Universidade Catolica Do Rio Grande Do Sul (PUCRS)	Porto Alegre	Rio Grande Do Sul	Brazil	90610-00
54	Clínica de Oncologia de Porto Alegre SS Ltda	Rio Grande	Rio Grande Do Sul	Brazil	90430-090
55	Instituto Joinvilense de Hematologia E Oncologia	Joinville	Santa Catarina	Brazil	89201-260
56	Fundação Pio XII Hospital de Câncer de Barretos	Barretos	Sao Paulo	Brazil	14784-400
57	Hospital das Clinicas - UNICAMP	Campinas	Sao Paulo	Brazil	13083-887
58	Fundação do ABC - Faculdade de Medicina do ABC	Santo André	Sao Paulo	Brazil	09060-650
59	Hospital Amaral Carvalho	Jaú	São Paulo	Brazil	17210-080
60	Instituto de Pesquisas Clínicas Para Estudos Multicêntricos	Caxias Do Sul		Brazil	95070-560
61	Instituto Do Câncer Do Ceará ICC	Fortaleza		Brazil	60430-230
62	Animi	Lages		Brazil	88501-001
63	Instituto Nacional de Câncer	Rio De Janeiro		Brazil	20231-050
64	Instituto COI de Pesquisa, Educação e Gestão	Rio De Janeiro		Brazil	22793-080
65	Hospital de Base Da Faculdade de Medicina de São José Do Rio Preto	São José Do Rio Preto		Brazil	15090-000
66	Hospital Alemão Oswaldo Cruz	São Paulo		Brazil	01323-903
67	Fundação Antônio Prudente - AC Camargo Câncer Center	São Paulo		Brazil	01509-900
68	Hospital Santa Marcelina	São Paulo		Brazil	08270-120
69	Corporacion de Beneficencia Osorno	Osorno	Los Lagos	Chile	5211092
70	Clinical Research Chile SpA	Valdivia	Los Rios	Chile	5110683
71	Fundación Arturo López Pérez (FALP) - PPDS	Santiago		Chile	7500713
72	Fundación Arturo López Pérez (FALP) - PPDS	Santiago		Chile	7500921
73	Sociedad Prosalud Montes y Orlandi Ltda	Santiago		Chile	7500921
74	Oncovida	Santiago		Chile	7510032
75	Clinica Santa Maria	Santiago		Chile	7520349
76	Centro Investigacion Clinica Del Sur	Temuco		Chile	4810371
77	Oncocentro APYS	Viña Del Mar		Chile	2520612
78	Centro de Investigaciones Clínicas Vina del Mar	Viña Del Mar		Chile	2540364
79	Prince of Wales Hospital	Hong Kong		Hong Kong	2031
80	Centro de Investigacion Clinica Chapultepec S.A. de C.V.	Morelia	Michoacan	Mexico	58260
81	Hospital Universitario Dr. Jose Eleuterio González	Monterrey	Nuevo Leon	Mexico	64060
82	Grupo Medico Camino	Ciudad de mexico		Mexico	03310
83	Accelerium, S. de R.L. de C.V.	Monterrey		Mexico	64000
84	Hospital Universitario Dr. Jose Eleuterio González	Monterrey		Mexico	64000
85	Unidad Médica Onco-Hematológica	Puebla		Mexico	CP 72530
86	SOMECO Sociedad de Metabolismo y Corazón S.C.	Veracruz		Mexico	91900
87	Farmacooncologia Especializada SA de CV	Zapopan		Mexico	45050
88	Auckland City Hospital	Auckland		New Zealand	1023
89	Christchurch Hospital	Christchurch		New Zealand	8011
90	Clinica Peruana Americana	Trujillo	La LIbertad	Peru	44
91	Clinica Internacional - PPDS	Lima		Peru	1
92	Hospital Nacional Cayetano Heredia	Lima		Peru	27
93	Aliada	Lima		Peru	34
94	Altay Regional Oncology Center	Barnaul		Russian Federation	656049
95	Chelyabinsk Regional Clinical Oncology Dispensary	Chelyabinsk		Russian Federation	454087
96	LLC Evimed	Chelyabinsk		Russian Federation	454087
97	Kursk Regional Oncology Centre	Kursk		Russian Federation	305035
98	Central Clinical Hospital With Polyclinic of President Administration of RF	Moscow		Russian Federation	121356
99	Federal State Institution Medical Radiology Research Center	Obninsk		Russian Federation	249036
100	Clinical Oncology Dispensary	Omsk		Russian Federation	644013
101	PMI Euromedservice	Pushkin		Russian Federation	196603
102	Hospital Orkli LLC	Saint Petersburg		Russian Federation	194044
103	Railway Clinical Hospital JSC RZhD	Saint Petersburg		Russian Federation	195271
104	Hospital Orkli LLC	Saint Petersburg		Russian Federation	199178
105	State Institution of Healthcare "Volgograd Regional Urology and Nephrology Centre"	Volzhskiy		Russian Federation	404120
106	Regional Clinical Oncology Hospital	Yaroslavl		Russian Federation	150040
107	National Cancer Centre	Singapore		Singapore	169610
108	Oncocare Cancer Centre	Singapore		Singapore	258499
109	Tan Tock Seng Hospital	Singapore		Singapore	308433