Study of XL092 + Nivolumab vs Sunitinib in Subjects With Advanced or Metastatic Non-Clear Cell Renal Cell Carcinoma

NCT05678673 | Active Not Recruiting Phase 3 DMC FDA Drug

• 2 other identifiers: XL092-304EU CTR: 2022-501703-27-0
• Study Type: interventional
• Target: 317
• Locations: 25 countries
• Sites: 163

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.

Conditions

Non-Clear Cell Renal Cell Carcinoma

Outcome Measures

Primary Outcomes (2)

• 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)

  Defined as the time from randomization to the earlier of either radiographic PD per RECIST 1.1 as determined by the BIRC or death from any cause

  Approximately 27 months after the first subject is randomized

• Objective response rate (ORR) as assessed by BIRC per RECIST 1.1

  Defined as the proportion of subjects with the best overall response of complete response (CR) or partial response (PR) per RECIST 1.1 as determined by the BIRC that is confirmed at a follow-up assessment ≥ 28 days later

  Up to 24 months after the first subject is randomized

Secondary Outcomes (1)

• Duration of Overall Survival (OS)

  Approximately 46 months after the first subject is randomized

Study Arms (2)

XL092 + Nivolumab

EXPERIMENTAL

Subjects with advanced or metastatic nccRCC will receive XL092 + nivolumab

Drug: XL092; Drug: Nivolumab

Sunitinib Malate

ACTIVE COMPARATOR

Subjects with advanced or metastatic nccRCC will receive an active comparator of sunitinib

Drug: Sunitinib Malate

Interventions

XL092 DRUG

Specified doses on specified days

XL092 + Nivolumab

Nivolumab DRUG

Specified doses on specified days

Also known as: Opdivo®

XL092 + Nivolumab

Sunitinib Malate DRUG

Specified doses on specified days

Also known as: Sutent®

Sunitinib Malate

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Exelixis: lead

Study Sites (163)

Exelixis Clinical Site #1

Duarte, California, 91010, United States

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Exelixis Clinical Site #164

Newport Beach, California, 92663, United States

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Exelixis Clinical Site #162

San Francisco, California, 94115, United States

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Exelixis Clinical Site #163

Aurora, Colorado, 80045, United States

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Exelixis Clinical Site #55

Jacksonville, Florida, 32209, United States

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Exelixis Clinical Site #161

Buffalo, New York, 14263, United States

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Exelixis Clinical Site #58

New York, New York, 10029, United States

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Exelixis Clinical Site #15

New York, New York, 10065, United States

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Exelixis Clinical Site #42

Cleveland, Ohio, 44106, United States

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Exelixis Clinical Site #31

Dallas, Texas, 75246, United States

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Exelixis Clinical Site #88

Pilar, Buenos Aires, B1629ODT, Argentina

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Exelixis Clinical Site #89

Viedma, Río Negro Province, R8500ACE, Argentina

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Exelixis Clinical Site #44

Buenos Aires, B7600FZO, Argentina

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Exelixis Clinical Site #35

CABA, C1419GEP, Argentina

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Exelixis Clinical Site #90

Córdoba, X5004BAL, Argentina

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Exelixis Clinical Site #51

Santa Fe, 2000, Argentina

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Exelixis Clinical Site #94

Albury, New South Wales, 2640, Australia

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Exelixis Clinical Site #97

Camperdown, New South Wales, 3021, Australia

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Exelixis Clinical Site #98

Liverpool, New South Wales, 2170, Australia

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Exelixis Clinical Site #95

Macquarie, New South Wales, 2109, Australia

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Exelixis Clinical Site #92

Sydney, New South Wales, 2145, Australia

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Exelixis Clinical Site #93

Waratah, New South Wales, 2298, Australia

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Exelixis Clinical Site #99

Douglas, Queensland, 4814, Australia

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Exelixis Clinical Site #100

Elizabeth Vale, South Australia, 5112, Australia

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Exelixis Clinical Site #91

Box Hill, Victoria, 3128, Australia

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Exelixis Clinical Site #96

St Albans, Victoria, 3021, Australia

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Exelixis Clinical Site #14

Chermside, 4032, Australia

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Exelixis Clinical Site #29

South Brisbane, 4101, Australia

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Exelixis Clinical Site #102

Porto Alegre, Rio Grande do Sul, 90035-903, Brazil

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Exelixis Clinical Site #68

Barretos, 14784 400, Brazil

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Exelixis Clinical Site #39

Itajaí, 88301-220, Brazil

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Exelixis Clinical Site #69

Passo Fundo, 99010-090, Brazil

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Exelixis Clinical Site #70

Porto Alegre, 90110-270, Brazil

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Exelixis Clinical Site #78

Porto Alegre, 91350-200, Brazil

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Exelixis Clinical Site #87

Santo André, 09060-870, Brazil

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Exelixis Clinical Site #50

São José do Rio Preto, 15090-000, Brazil

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Exelixis Clinical Site #101

São Paulo, 01246-000, Brazil

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Exelixis Clinical Site #81

São Paulo, 01323-001, Brazil

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Exelixis Clinical Site #85

São Paulo, 01323-903, Brazil

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Exelixis Clinical Site #43

São Paulo, 17210-120, Brazil

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Exelixis Clinical Site #104

Plovdiv, 4004, Bulgaria

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Exelixis Clinical Site #105

Sofia, 1404, Bulgaria

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Exelixis Clinical Site #103

Sofia, 1431, Bulgaria

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Exelixis Clinical Site #53

Providencia, 7520378, Chile

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Exelixis Clinical Site #106

Santiago, 7500921, Chile

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Exelixis Clinical Site #108

Santiago, 7520378, Chile

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Exelixis Clinical Site #109

Santiago, 8241479, Chile

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Exelixis Clinical Site #107

Santiago, 8420383, Chile

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Exelixis Clinical Site #111

Rijeka, 51000, Croatia

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Exelixis Clinical Site #110

Zagreb, 10000, Croatia

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Exelixis Clinical Site #61

Brno, 602 00, Czechia

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Exelixis Clinical Site #112

Olomouc, 77900, Czechia

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Exelixis Clinical Site #27

Prague, 140 59, Czechia

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Exelixis Clinical Site #86

Prague, 150 06, Czechia

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Exelixis Clinical Site #71

Helsinki, 00290, Finland

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Exelixis Clinical Site #115

Angers, Maine Et Loire, 49933, France

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Exelixis Clinical Site #74

Caen, 14076, France

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Exelixis Clinical Site #66

Clermont-Ferrand, 63011, France

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Exelixis Clinical Site #40

Créteil, 94010, France

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Exelixis Clinical Site #38

Le Mans, 72000, France

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Exelixis Clinical Site #114

Lille, 59020, France

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Exelixis Clinical Site #113

Lyon, 08Rhone69373, France

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Exelixis Clinical Site #36

Marseille, 13385, France

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Exelixis Clinical Site #12

Paris, 75013, France

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Exelixis Clinical Site #67

Paris, 75475, France

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Exelixis Clinical Site #76

Pierre-Bénite, 69310, France

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Exelixis Clinical Site #59

Reims, 51726, France

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Exelixis Clinical Site #28

Rennes, 35042, France

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Exelixis Clinical Site #41

Strasbourg, 67200, France

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Exelixis Clinical Site #65

Suresnes, 92150, France

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Exelixis Clinical Site #116

Frankfurt am Main, Hesse, 60590, Germany

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Exelixis Clinical Site #79

Eisleben Lutherstadt, 06295, Germany

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Exelixis Clinical Site #117

Hamburg, 22763, Germany

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Exelixis Clinical Site #118

Athens, 11528, Greece

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Exelixis Clinical Site #119

Athens, 12462, Greece

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Exelixis Clinical Site #123

Athens, 12462, Greece

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Exelixis Clinical Site #121

Thessaloniki, 54622, Greece

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Exelixis Clinical Site #120

Thessaloniki, 56403, Greece

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Exelixis Clinical Site #122

Tripoli, 22131, Greece

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Exelixis Clinical Site #124

Hong Kong, Hong Kong

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Exelixis Clinical Site #125

Hong Kong, Hong Kong

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Exelixis Clinical Site #128

Budapest, 1082, Hungary

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Exelixis Clinical Site #127

Budapest, 1122, Hungary

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Exelixis Clinical Site #126

Debrecen, 4032, Hungary

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Exelixis Clinical Site #130

Rozzano, Milano, 20089, Italy

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Exelixis Clinical Site #131

Candiolo, Torino, 10060, Italy

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Exelixis Clinical Site #7

Arezzo, 52100, Italy

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Exelixis Clinical Site #132

Bari, 70124, Italy

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Exelixis Clinical Site #26

Brescia, 25123, Italy

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Exelixis Clinical Site #19

Meldola, 47014, Italy

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Exelixis Clinical Site #129

Milan, 20132, Italy

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Exelixis Clinical Site #30

Napoli, 80131, Italy

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Exelixis Clinical Site #37

Pavia, 27100, Italy

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Exelixis Clinical Site #63

Pisa, 56126, Italy

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Exelixis Clinical Site #48

Reggio Emilia, 42123, Italy

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Exelixis Clinical Site #60

Roma, 00168, Italy

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Exelixis Clinical Site #72

San Giovanni Rotondo, 71013, Italy

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Exelixis Clinical Site #17

Verona, 37134, Italy

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Exelixis Clinical Site #54

Kuala Lumpur, 50586, Malaysia

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Exelixis Clinical Site #24

Kuala Lumpur, 59100, Malaysia

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Exelixis Clinical Site #46

Putrajaya, 62250, Malaysia

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Exelixis Clinical Site #64

Eindhoven, 631BM, Netherlands

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Exelixis Clinical Site #45

Bydgoszcz, 85-796, Poland

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Exelixis Clinical Site #49

Gdansk, 80-219, Poland

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Exelixis Clinical Site #33

Otwock, 05-400, Poland

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Exelixis Clinical Site #77

Poznan, 02-781, Poland

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Exelixis Clinical Site #133

Poznan, 60-569, Poland

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Exelixis Clinical Site #80

Poznan, 60-693, Poland

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Exelixis Clinical Site #23

Rzeszów, 35-021, Poland

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Exelixis Clinical Site #134

Singapore, 168583, Singapore

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Exelixis Clinical Site #137

Banská Bystrica, 97517, Slovakia

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Exelixis Clinical Site #135

Bratislava, 83310, Slovakia

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Exelixis Clinical Site #136

Košice, 04190, Slovakia

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Exelixis Clinical Site #11

Busan, 49201, South Korea

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Exelixis Clinical Site #32

Busan, 49267, South Korea

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Exelixis Clinical Site #22

Daegu, 42601, South Korea

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Exelixis Clinical Site #13

Daejeon, 35015, South Korea

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Exelixis Clinical Site #16

Goyang-si, 10408, South Korea

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Exelixis Clinical Site #25

Gyeonggi-do, 16247, South Korea

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Exelixis Clinical Site #21

Seongnam-si, 13496, South Korea

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Exelixis Clinical Site #5

Seongnam-si, 13620, South Korea

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Exelixis Clinical Site #10

Seoul, 02841, South Korea

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Exelixis Clinical Site #4

Seoul, 03722, South Korea

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Exelixis Clinical Site #47

Seoul, 05505, South Korea

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Exelixis Clinical Site #6

Seoul, 06351, South Korea

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Exelixis Clinical Site #20

Seoul, 06591, South Korea

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Exelixis Clinical Site #143

Palma de Mallorca, Balearic Islands, 7120, Spain

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Exelixis Clinical Site #142

Majadahonda, Madrid, 28220, Spain

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Exelixis Clinical Site #56

Barcelona, 08035, Spain

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Exelixis Clinical Site #9

Barcelona, 08036, Spain

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Exelixis Clinical Site #52

Barcelona, 08041, Spain

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Exelixis Clinical Site #138

Barcelona, 8906, Spain

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Exelixis Clinical Site #141

Córdoba, 14004, Spain

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Exelixis Clinical Site #62

Girona, 17007, Spain

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Exelixis Clinical Site #139

Madrid, 28009, Spain

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Exelixis Clinical Site #140

Madrid, 28033, Spain

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Exelixis Clinical Site #3

Madrid, 28034, Spain

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Exelixis Clinical Site #34

Madrid, 28041, Spain

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Exelixis Clinical Site #8

Madrid, 28046, Spain

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Exelixis Clinical Site #145

Málaga, 29011, Spain

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Exelixis Clinical Site #57

Oviedo, 33011, Spain

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Exelixis Clinical Site #75

Santander, 39008, Spain

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Exelixis Clinical Site #144

Seville, 41009, Spain

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Exelixis Clinical Site #18

Seville, 41013, Spain

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Exelixis Clinical Site #73

Valencia, 46009, Spain

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Exelixis Clinical Site #147

Bangkok Noi, Bangkok, 10400, Thailand

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Exelixis Clinical Site #146

Phu Wiang, Changwat Khon Kaen, 40002, Thailand

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Exelixis Clinical Site #84

Bangkok, 10330, Thailand

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Exelixis Clinical Site #83

Bangkok, 10400, Thailand

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Exelixis Clinical Site #82

Chiang Mai, 50200, Thailand

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Exelixis Clinical Site #157

Adana, 1140, Turkey (Türkiye)

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Exelixis Clinical Site #153

Adana, 1230, Turkey (Türkiye)

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Exelixis Clinical Site #156

Ankara, 06520, Turkey (Türkiye)

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Exelixis Clinical Site #149

Ankara, 6010, Turkey (Türkiye)

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Exelixis Clinical Site #150

Ankara, 6230, Turkey (Türkiye)

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Exelixis Clinical Site #155

Ankara, 6590, Turkey (Türkiye)

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Exelixis Clinical Site #152

Ankara, 6800, Turkey (Türkiye)

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Exelixis Clinical Site #151

Istanbul, 34722, Turkey (Türkiye)

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Exelixis Clinical Site #148

Istanbul, 34890, Turkey (Türkiye)

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Exelixis Clinical Site #154

Izmir, 35575, Turkey (Türkiye)

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Exelixis Clinical Site #158

Sheffield, South Yorkshire, S10 2SJ, United Kingdom

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Exelixis Clinical Site #160

London, EC1M 6BQ, United Kingdom

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Exelixis Clinical Site #159

London, SE1 9RT, United Kingdom

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Related Publications (1)

• Pal SK, Powles T, Kanesvaran R, Molina-Cerrillo J, Feldman DR, Barata P, Liu M, Bhatt A, Wang Z, Nandoskar P, Suarez C. STELLAR-304: a phase III study of zanzalintinib (XL092) plus nivolumab in advanced non-clear cell renal cell carcinoma. Future Oncol. 2025 Mar;21(7):787-794. doi: 10.1080/14796694.2025.2458395. Epub 2025 Feb 26.

  PMID: 40008409 DERIVED

MeSH Terms

Interventions

Nivolumab; Sunitinib

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Pyrroles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 23, 2022
• First Posted: January 10, 2023
• Study Start: January 1, 2023
• Primary Completion: July 1, 2025
• Study Completion (Estimated): June 1, 2028
• Last Updated: July 14, 2025

Record last verified: 2025-07

Data Sharing

• IPD Sharing: Will not share

Locations

NL (1); AU (12); KR (13); AR (6); PL (7); ES (19); FI (1); DE (3); US (10); CR (2); HK (2); BR (12); MY (3); SG (1); BU (3); TH (5); GR (6); IT (14); SL (3); TU (10); CL (5); FR (15); CZ (4); HU (3); GB (3)