Clinical trial NCT05678673: Study of XL092 + Nivolumab vs Sunitinib in Subjects With Advanced or Metastatic Non-Clear Cell Renal Cell Carcinoma
Official title: A Randomized Open-Label Phase 3 Study of XL092 + Nivolumab vs Sunitinib in Subjects With Advanced or Metastatic Non-Clear Cell Renal Cell Carcinoma
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: Non-Clear Cell Renal Cell Carcinoma
Lead sponsor: Exelixis
Sponsor class: INDUSTRY
First posted: 2023-01-10
Enrollment: 291
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This is a multicenter, randomized (2:1), open-label, controlled Phase 3 trial of XL092 in combination with nivolumab versus sunitinib in subjects with unresectable, locally advanced or metastatic nccRCC who have not received prior systemic anticancer therapy.


Eligibility criteria: Inclusion Criteria:

* Histologically confirmed nccRCC that is unresectable, advanced or metastatic. Histologic subtypes including papillary, unclassified, and translocation-associated are allowed. Among the eligible histologic subtypes, sarcomatoid features are allowed.
* Measurable disease according to RECIST v1.1 as determined by the Investigator.
* Available archival tumor biopsy material.
* Recovery to baseline or ≤ Grade 1 per CTCAE v5 from AE(s) related to any prior treatments unless AE(s) are deemed clinically nonsignificant by the Investigator and/or stable on supportive therapy.
* Age 18 years or older on the day of consent.
* Karnofsky Performance Status (KPS) ≥ 70%.
* Adequate organ and marrow function within 14 days prior to randomization.
* Sexually active fertile subjects and their partners must agree to use highly effective methods of contraception.
* Female subjects of childbearing potential must not be pregnant at screening.

Exclusion Criteria:

* Chromophobe, renal medullary carcinoma, and pure collecting duct histologic subtypes of nccRCC.
* Prior systemic anticancer therapy for unresectable locally advanced or metastatic nccRCC including investigational agents.

  * Note: One prior systemic adjuvant therapy, including immune checkpoint inhibitor therapy and excluding sunitinib, is allowed for completely resected RCC and if recurrence occurred at least 6 months after the last dose of adjuvant therapy.
* Radiation therapy for bone metastases within 2 weeks, any other radiation therapy within 4 weeks prior to randomization.
* Known brain metastases or cranial epidural disease unless adequately treated with radiotherapy (including radiosurgery) or surgically removed and stable for at least 4 weeks before randomization.
* Concomitant anticoagulation with oral anticoagulants and platelet inhibitors. Subjects who are receiving oral anticoagulants at the time of screening must be transitioned to LMWH prior to randomization. Subjects who require treatment with platelet inhibitors are not eligible.
* Major surgery (eg, GI surgery, removal or biopsy of brain metastasis) within 8 weeks prior to randomization. Prior laparoscopic nephrectomy within 4 weeks prior to randomization. Minor surgery (eg, simple excision, tooth extraction) within 10 days before randomization. Complete wound healing from major or minor surgery must have occurred at least prior to randomization.

  * Note: Fresh tumor biopsies should be performed at least 7 days before randomization. Subjects with clinically relevant ongoing complications from prior surgical procedures, including biopsies, are not eligible.
* Corrected QT interval calculated by the Fridericia formula (QTcF) \> 480 ms per electrocardiogram (ECG) within 14 days before randomization.
* Pregnant or lactating females.
* Administration of a live, attenuated vaccine within 30 days before randomization.

  * Note: If feasible, approved non-live vaccines for SARS-CoV-2 should be administered at least 2 weeks before randomization.

Primary outcomes:
measure: Duration of Progression-free survival (PFS) per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1), by Blinded Independent Radiology Committee (BIRC)
timeFrame: Approximately 27 months after the first subject is randomized
measure: Objective response rate (ORR) as assessed by BIRC per RECIST 1.1
timeFrame: Up to 24 months after the first subject is randomized
Secondary outcomes:
measure: Duration of Overall Survival (OS)
timeFrame: Approximately 46 months after the first subject is randomized
Other outcomes:
Locations:
city: Duarte
country: United States
facility: Exelixis Clinical Site #1
state: California
city: Newport Beach
country: United States
facility: Exelixis Clinical Site #164
state: California
city: San Francisco
country: United States
facility: Exelixis Clinical Site #162
state: California
city: Aurora
country: United States
facility: Exelixis Clinical Site #163
state: Colorado
city: Jacksonville
country: United States
facility: Exelixis Clinical Site #55
state: Florida
city: Buffalo
country: United States
facility: Exelixis Clinical Site #161
state: New York
city: New York
country: United States
facility: Exelixis Clinical Site #58
state: New York
city: New York
country: United States
facility: Exelixis Clinical Site #15
state: New York
city: Cleveland
country: United States
facility: Exelixis Clinical Site #42
state: Ohio
city: Knoxville
country: United States
facility: Exelixis Clinical Site #2
state: Tennessee
city: Dallas
country: United States
facility: Exelixis Clinical Site #31
state: Texas
city: Pilar
country: Argentina
facility: Exelixis Clinical Site #88
state: Buenos Aires
city: Viedma
country: Argentina
facility: Exelixis Clinical Site #89
state: Rio Negro
city: Buenos Aires
country: Argentina
facility: Exelixis Clinical Site #44
city: Caba
country: Argentina
facility: Exelixis Clinical Site #35
city: Córdoba
country: Argentina
facility: Exelixis Clinical Site #90
city: Santa Fe
country: Argentina
facility: Exelixis Clinical Site #51
city: Albury
country: Australia
facility: Exelixis Clinical Site #94
state: New South Wales
city: Camperdown
country: Australia
facility: Exelixis Clinical Site #97
state: New South Wales
city: Liverpool
country: Australia
facility: Exelixis Clinical Site #98
state: New South Wales
city: Macquarie
country: Australia
facility: Exelixis Clinical Site #95
state: New South Wales
city: Sydney
country: Australia
facility: Exelixis Clinical Site #92
state: New South Wales
city: Waratah
country: Australia
facility: Exelixis Clinical Site #93
state: New South Wales
city: Douglas
country: Australia
facility: Exelixis Clinical Site #99
state: Queensland
city: Elizabeth Vale
country: Australia
facility: Exelixis Clinical Site #100
state: South Australia
city: Box Hill
country: Australia
facility: Exelixis Clinical Site #91
state: Victoria
city: St Albans
country: Australia
facility: Exelixis Clinical Site #96
state: Victoria
city: Chermside
country: Australia
facility: Exelixis Clinical Site #14
city: South Brisbane
country: Australia
facility: Exelixis Clinical Site #29
city: Porto Alegre
country: Brazil
facility: Exelixis Clinical Site #102
state: Rio Grande Do Sul
city: Barretos
country: Brazil
facility: Exelixis Clinical Site #68
city: Itajaí
country: Brazil
facility: Exelixis Clinical Site #39
city: Passo Fundo
country: Brazil
facility: Exelixis Clinical Site #69
city: Porto Alegre
country: Brazil
facility: Exelixis Clinical Site #70
city: Porto Alegre
country: Brazil
facility: Exelixis Clinical Site #78
city: Santo André
country: Brazil
facility: Exelixis Clinical Site #87
city: Sao Paulo
country: Brazil
facility: Exelixis Clinical Site #43
city: São José Do Rio Preto
country: Brazil
facility: Exelixis Clinical Site #50
city: São Paulo
country: Brazil
facility: Exelixis Clinical Site #101
city: São Paulo
country: Brazil
facility: Exelixis Clinical Site #81
city: São Paulo
country: Brazil
facility: Exelixis Clinical Site #85
city: Plovdiv
country: Bulgaria
facility: Exelixis Clinical Site #104
city: Sofia
country: Bulgaria
facility: Exelixis Clinical Site #105
city: Sofia
country: Bulgaria
facility: Exelixis Clinical Site #103
city: Providencia
country: Chile
facility: Exelixis Clinical Site #53
city: Santiago
country: Chile
facility: Exelixis Clinical Site #106
city: Santiago
country: Chile
facility: Exelixis Clinical Site #108
city: Santiago
country: Chile
facility: Exelixis Clinical Site #109
city: Santiago
country: Chile
facility: Exelixis Clinical Site #107
city: Rijeka
country: Croatia
facility: Exelixis Clinical Site #111
city: Zagreb
country: Croatia
facility: Exelixis Clinical Site #110
city: Brno
country: Czechia
facility: Exelixis Clinical Site #61
city: Olomouc
country: Czechia
facility: Exelixis Clinical Site #112
city: Praha 4
country: Czechia
facility: Exelixis Clinical Site #27
city: Praha 5
country: Czechia
facility: Exelixis Clinical Site #86
city: Helsinki
country: Finland
facility: Exelixis Clinical Site #71
city: Angers Cedex
country: France
facility: Exelixis Clinical Site #115
state: Maine Et Loire
city: Caen Cedex
country: France
facility: Exelixis Clinical Site #74
city: Clermont-Ferrand
country: France
facility: Exelixis Clinical Site #66
city: Creteil
country: France
facility: Exelixis Clinical Site #40
city: Le Mans
country: France
facility: Exelixis Clinical Site #38
city: Lille Cedex
country: France
facility: Exelixis Clinical Site #114
city: Lyon Cedex
country: France
facility: Exelixis Clinical Site #113
city: Marseille
country: France
facility: Exelixis Clinical Site #36
city: Paris Cedex
country: France
facility: Exelixis Clinical Site #67
city: Paris
country: France
facility: Exelixis Clinical Site #12
city: Pierre-Bénite
country: France
facility: Exelixis Clinical Site #76
city: Reims cedex
country: France
facility: Exelixis Clinical Site #59
city: Rennes
country: France
facility: Exelixis Clinical Site #28
city: Strasbourg
country: France
facility: Exelixis Clinical Site #41
city: Suresnes
country: France
facility: Exelixis Clinical Site #65
city: Frankfurt
country: Germany
facility: Exelixis Clinical Site #116
state: Hessen
city: Hamburg
country: Germany
facility: Exelixis Clinical Site #117
city: Lutherstadt Eisleben
country: Germany
facility: Exelixis Clinical Site #79
city: Athens
country: Greece
facility: Exelixis Clinical Site #118
city: Athens
country: Greece
facility: Exelixis Clinical Site #119
city: Athens
country: Greece
facility: Exelixis Clinical Site #123
city: Thessaloníki
country: Greece
facility: Exelixis Clinical Site #121
city: Thessaloníki
country: Greece
facility: Exelixis Clinical Site #120
city: Trípoli
country: Greece
facility: Exelixis Clinical Site #122
city: Hong Kong
country: Hong Kong
facility: Exelixis Clinical Site #124
city: Hong Kong
country: Hong Kong
facility: Exelixis Clinical Site #125
city: Budapest
country: Hungary
facility: Exelixis Clinical Site #128
city: Budapest
country: Hungary
facility: Exelixis Clinical Site #127
city: Debrecen
country: Hungary
facility: Exelixis Clinical Site #126
city: Rozzano
country: Italy
facility: Exelixis Clinical Site #130
state: Milano
city: Candiolo
country: Italy
facility: Exelixis Clinical Site #131
state: Torino
city: Arezzo
country: Italy
facility: Exelixis Clinical Site #7
city: Bari
country: Italy
facility: Exelixis Clinical Site #132
city: Brescia
country: Italy
facility: Exelixis Clinical Site #26
city: Meldola
country: Italy
facility: Exelixis Clinical Site #19
city: Milano
country: Italy
facility: Exelixis Clinical Site #129
city: Napoli
country: Italy
facility: Exelixis Clinical Site #30
city: Pavia
country: Italy
facility: Exelixis Clinical Site #37
city: Pisa
country: Italy
facility: Exelixis Clinical Site #63
city: Reggio Emilia
country: Italy
facility: Exelixis Clinical Site #48
city: Roma
country: Italy
facility: Exelixis Clinical Site #60
city: San Giovanni Rotondo
country: Italy
facility: Exelixis Clinical Site #72
city: Verona
country: Italy
facility: Exelixis Clinical Site #17
city: Busan
country: Korea, Republic of
facility: Exelixis Clinical Site #11
city: Busan
country: Korea, Republic of
facility: Exelixis Clinical Site #32
city: Daegu
country: Korea, Republic of
facility: Exelixis Clinical Site #22
city: Daejeon
country: Korea, Republic of
facility: Exelixis Clinical Site #13
city: Goyang-si
country: Korea, Republic of
facility: Exelixis Clinical Site #16
city: Gyeonggi-do
country: Korea, Republic of
facility: Exelixis Clinical Site #25
city: Seongnam-si
country: Korea, Republic of
facility: Exelixis Clinical Site #21
city: Seongnam-si
country: Korea, Republic of
facility: Exelixis Clinical Site #5
city: Seoul
country: Korea, Republic of
facility: Exelixis Clinical Site #10
city: Seoul
country: Korea, Republic of
facility: Exelixis Clinical Site #4
city: Seoul
country: Korea, Republic of
facility: Exelixis Clinical Site #47
city: Seoul
country: Korea, Republic of
facility: Exelixis Clinical Site #6
city: Seoul
country: Korea, Republic of
facility: Exelixis Clinical Site #20
city: Kuala Lumpur
country: Malaysia
facility: Exelixis Clinical Site #54
city: Kuala Lumpur
country: Malaysia
facility: Exelixis Clinical Site #24
city: Putrajaya
country: Malaysia
facility: Exelixis Clinical Site #46
city: Eindhoven
country: Netherlands
facility: Exelixis Clinical Site #64
city: Bydgoszcz
country: Poland
facility: Exelixis Clinical Site #45
city: Gdańsk
country: Poland
facility: Exelixis Clinical Site #49
city: Otwock
country: Poland
facility: Exelixis Clinical Site #33
city: Poznań
country: Poland
facility: Exelixis Clinical Site #77
city: Poznań
country: Poland
facility: Exelixis Clinical Site #133
city: Poznań
country: Poland
facility: Exelixis Clinical Site #80
city: Rzeszow
country: Poland
facility: Exelixis Clinical Site #23
city: Singapore
country: Singapore
facility: Exelixis Clinical Site #134
city: Banská Bystrica
country: Slovakia
facility: Exelixis Clinical Site #137
city: Bratislava
country: Slovakia
facility: Exelixis Clinical Site #135
city: Košice
country: Slovakia
facility: Exelixis Clinical Site #136
city: Palma De Mallorca
country: Spain
facility: Exelixis Clinical Site #143
state: Baleares
city: Majadahonda
country: Spain
facility: Exelixis Clinical Site #142
state: Madrid
city: Barcelona
country: Spain
facility: Exelixis Clinical Site #56
city: Barcelona
country: Spain
facility: Exelixis Clinical Site #9
city: Barcelona
country: Spain
facility: Exelixis Clinical Site #52
city: Barcelona
country: Spain
facility: Exelixis Clinical Site #138
city: Córdoba
country: Spain
facility: Exelixis Clinical Site #141
city: Girona
country: Spain
facility: Exelixis Clinical Site #62
city: Madrid
country: Spain
facility: Exelixis Clinical Site #139
city: Madrid
country: Spain
facility: Exelixis Clinical Site #140
city: Madrid
country: Spain
facility: Exelixis Clinical Site #3
city: Madrid
country: Spain
facility: Exelixis Clinical Site #34
city: Madrid
country: Spain
facility: Exelixis Clinical Site #8
city: Málaga
country: Spain
facility: Exelixis Clinical Site #145
city: Oviedo
country: Spain
facility: Exelixis Clinical Site #57
city: Santander
country: Spain
facility: Exelixis Clinical Site #75
city: Sevilla
country: Spain
facility: Exelixis Clinical Site #144
city: Sevilla
country: Spain
facility: Exelixis Clinical Site #18
city: Valencia
country: Spain
facility: Exelixis Clinical Site #73
city: Bangkok Noi
country: Thailand
facility: Exelixis Clinical Site #147
state: Bangkok
city: Nai Muang
country: Thailand
facility: Exelixis Clinical Site #146
state: Khon Kaen
city: Bangkok
country: Thailand
facility: Exelixis Clinical Site #84
city: Bangkok
country: Thailand
facility: Exelixis Clinical Site #83
city: Chiang Mai
country: Thailand
facility: Exelixis Clinical Site #82
city: Adana
country: Turkey
facility: Exelixis Clinical Site #157
city: Adana
country: Turkey
facility: Exelixis Clinical Site #153
city: Ankara
country: Turkey
facility: Exelixis Clinical Site #156
city: Ankara
country: Turkey
facility: Exelixis Clinical Site #149
city: Ankara
country: Turkey
facility: Exelixis Clinical Site #150
city: Ankara
country: Turkey
facility: Exelixis Clinical Site #155
city: Ankara
country: Turkey
facility: Exelixis Clinical Site #152
city: Istanbul
country: Turkey
facility: Exelixis Clinical Site #151
city: Istanbul
country: Turkey
facility: Exelixis Clinical Site #148
city: İzmir
country: Turkey
facility: Exelixis Clinical Site #154
city: Sheffield
country: United Kingdom
facility: Exelixis Clinical Site #158
state: South Yorkshire
city: London
country: United Kingdom
facility: Exelixis Clinical Site #160
city: London
country: United Kingdom
facility: Exelixis Clinical Site #159
Study officials:
References: