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

Phase 3

Recruiting

• Conditions: Non-Clear Cell Renal Cell Carcinoma
• Interventions: Drug: Sunitinib Malate; Drug: XL092; Drug: Nivolumab

• Registration Number: NCT05678673
• Lead Sponsor: Exelixis

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2022-12-23
• Study First Submitted QC: 2022-12-23
• Study Start: 2023-01-01
• Study First Posted: 2023-01-10
• Status Verified: 2024-12
• Last Update Submitted: 2024-12-12
• Last Update Posted: 2024-12-17
• Primary Completion: 2025-07
• Study Completion: 2028-06

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 291

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Sunitinib Malate	Sunitinib Malate	Subjects with advanced or metastatic nccRCC will receive an active comparator of sunitinib
XL092 + Nivolumab	Nivolumab	Subjects with advanced or metastatic nccRCC will receive XL092 + nivolumab
XL092 + Nivolumab	XL092	Subjects with advanced or metastatic nccRCC will receive XL092 + nivolumab

Primary Outcome Measures

Name	Time	Method
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)	Approximately 27 months after the first subject is randomized	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
Objective response rate (ORR) as assessed by BIRC per RECIST 1.1	Up to 24 months after the first subject is randomized	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

Secondary Outcome Measures

Name	Time	Method
Duration of Overall Survival (OS)	Approximately 46 months after the first subject is randomized	Defined as the time from randomization to death due to any cause

Trial Locations

Locations (164)

Exelixis Clinical Site #164; 🇺🇸 Newport Beach, California, United States

Exelixis Clinical Site #162; 🇺🇸 San Francisco, California, United States

Exelixis Clinical Site #163; 🇺🇸 Aurora, Colorado, United States

Exelixis Clinical Site #161; 🇺🇸 Buffalo, New York, United States

Exelixis Clinical Site #88; 🇦🇷 Pilar, Buenos Aires, Argentina

Exelixis Clinical Site #89; 🇦🇷 Viedma, Rio Negro, Argentina

Exelixis Clinical Site #90; 🇦🇷 Córdoba, Argentina

Exelixis Clinical Site #94; 🇦🇺 Albury, New South Wales, Australia

Exelixis Clinical Site #97; 🇦🇺 Camperdown, New South Wales, Australia

Exelixis Clinical Site #98; 🇦🇺 Liverpool, New South Wales, Australia

Exelixis Clinical Site #95; 🇦🇺 Macquarie, New South Wales, Australia

Exelixis Clinical Site #92; 🇦🇺 Sydney, New South Wales, Australia

Exelixis Clinical Site #93; 🇦🇺 Waratah, New South Wales, Australia

Exelixis Clinical Site #99; 🇦🇺 Douglas, Queensland, Australia

Exelixis Clinical Site #100; 🇦🇺 Elizabeth Vale, South Australia, Australia

Exelixis Clinical Site #91; 🇦🇺 Box Hill, Victoria, Australia

Exelixis Clinical Site #96; 🇦🇺 St Albans, Victoria, Australia

Exelixis Clinical Site #102; 🇧🇷 Porto Alegre, Rio Grande Do Sul, Brazil

Exelixis Clinical Site #101; 🇧🇷 São Paulo, Brazil

Exelixis Clinical Site #104; 🇧🇬 Plovdiv, Bulgaria

Exelixis Clinical Site #105; 🇧🇬 Sofia, Bulgaria

Exelixis Clinical Site #103; 🇧🇬 Sofia, Bulgaria

Exelixis Clinical Site #106; 🇨🇱 Santiago, Chile

Exelixis Clinical Site #108; 🇨🇱 Santiago, Chile

Exelixis Clinical Site #109; 🇨🇱 Santiago, Chile

Exelixis Clinical Site #107; 🇨🇱 Santiago, Chile

Exelixis Clinical Site #111; 🇭🇷 Rijeka, Croatia

Exelixis Clinical Site #110; 🇭🇷 Zagreb, Croatia

Exelixis Clinical Site #112; 🇨🇿 Olomouc, Czechia

Exelixis Clinical Site #115; 🇫🇷 Angers Cedex, Maine Et Loire, France

Exelixis Clinical Site #114; 🇫🇷 Lille Cedex, France

Exelixis Clinical Site #113; 🇫🇷 Lyon Cedex, France

Exelixis Clinical Site #116; 🇩🇪 Frankfurt, Hessen, Germany

Exelixis Clinical Site #117; 🇩🇪 Hamburg, Germany

Exelixis Clinical Site #118; 🇬🇷 Athens, Greece

Exelixis Clinical Site #119; 🇬🇷 Athens, Greece

Exelixis Clinical Site #123; 🇬🇷 Athens, Greece

Exelixis Clinical Site #121; 🇬🇷 Thessaloníki, Greece

Exelixis Clinical Site #120; 🇬🇷 Thessaloníki, Greece

Exelixis Clinical Site #122; 🇬🇷 Trípoli, Greece

Exelixis Clinical Site #124; 🇭🇰 Hong Kong, Hong Kong

Exelixis Clinical Site #125; 🇭🇰 Hong Kong, Hong Kong

Exelixis Clinical Site #128; 🇭🇺 Budapest, Hungary

Exelixis Clinical Site #127; 🇭🇺 Budapest, Hungary

Exelixis Clinical Site #126; 🇭🇺 Debrecen, Hungary

Exelixis Clinical Site #130; 🇮🇹 Rozzano, Milano, Italy

Exelixis Clinical Site #131; 🇮🇹 Candiolo, Torino, Italy

Exelixis Clinical Site #132; 🇮🇹 Bari, Italy

Exelixis Clinical Site #129; 🇮🇹 Milano, Italy

Exelixis Clinical Site #133; 🇵🇱 Poznań, Poland

Exelixis Clinical Site #134; 🇸🇬 Singapore, Singapore

Exelixis Clinical Site #137; 🇸🇰 Banská Bystrica, Slovakia

Exelixis Clinical Site #135; 🇸🇰 Bratislava, Slovakia

Exelixis Clinical Site #136; 🇸🇰 Košice, Slovakia

Exelixis Clinical Site #143; 🇪🇸 Palma De Mallorca, Baleares, Spain

Exelixis Clinical Site #142; 🇪🇸 Majadahonda, Madrid, Spain

Exelixis Clinical Site #138; 🇪🇸 Barcelona, Spain

Exelixis Clinical Site #141; 🇪🇸 Córdoba, Spain

Exelixis Clinical Site #139; 🇪🇸 Madrid, Spain

Exelixis Clinical Site #140; 🇪🇸 Madrid, Spain

Exelixis Clinical Site #145; 🇪🇸 Málaga, Spain

Exelixis Clinical Site #144; 🇪🇸 Sevilla, Spain

Exelixis Clinical Site #147; 🇹🇭 Bangkok Noi, Bangkok, Thailand

Exelixis Clinical Site #146; 🇹🇭 Nai Muang, Khon Kaen, Thailand

Exelixis Clinical Site #157; 🇹🇷 Adana, Turkey

Exelixis Clinical Site #153; 🇹🇷 Adana, Turkey

Exelixis Clinical Site #156; 🇹🇷 Ankara, Turkey

Exelixis Clinical Site #149; 🇹🇷 Ankara, Turkey

Exelixis Clinical Site #150; 🇹🇷 Ankara, Turkey

Exelixis Clinical Site #155; 🇹🇷 Ankara, Turkey

Exelixis Clinical Site #152; 🇹🇷 Ankara, Turkey

Exelixis Clinical Site #151; 🇹🇷 Istanbul, Turkey

Exelixis Clinical Site #148; 🇹🇷 Istanbul, Turkey

Exelixis Clinical Site #154; 🇹🇷 İzmir, Turkey

Exelixis Clinical Site #158; 🇬🇧 Sheffield, South Yorkshire, United Kingdom

Exelixis Clinical Site #160; 🇬🇧 London, United Kingdom

Exelixis Clinical Site #159; 🇬🇧 London, United Kingdom

Exelixis Clinical Site #1; 🇺🇸 Duarte, California, United States

Exelixis Clinical Site #55; 🇺🇸 Jacksonville, Florida, United States

Exelixis Clinical Site #58; 🇺🇸 New York, New York, United States

Exelixis Clinical Site #15; 🇺🇸 New York, New York, United States

Exelixis Clinical Site #42; 🇺🇸 Cleveland, Ohio, United States

Exelixis Clinical Site #2; 🇺🇸 Knoxville, Tennessee, United States

Exelixis Clinical Site #31; 🇺🇸 Dallas, Texas, United States

Exelixis Clinical Site #44; 🇦🇷 Buenos Aires, Argentina

Exelixis Clinical Site #35; 🇦🇷 Caba, Argentina

Exelixis Clinical Site #51; 🇦🇷 Santa Fe, Argentina

Exelixis Clinical Site #14; 🇦🇺 Chermside, Australia

Exelixis Clinical Site #29; 🇦🇺 South Brisbane, Australia

Exelixis Clinical Site #68; 🇧🇷 Barretos, Brazil

Exelixis Clinical Site #39; 🇧🇷 Itajaí, Brazil

Exelixis Clinical Site #69; 🇧🇷 Passo Fundo, Brazil

Exelixis Clinical Site #70; 🇧🇷 Porto Alegre, Brazil

Exelixis Clinical Site #78; 🇧🇷 Porto Alegre, Brazil

Exelixis Clinical Site #87; 🇧🇷 Santo André, Brazil

Exelixis Clinical Site #43; 🇧🇷 Sao Paulo, Brazil

Exelixis Clinical Site #50; 🇧🇷 São José Do Rio Preto, Brazil

Exelixis Clinical Site #81; 🇧🇷 São Paulo, Brazil

Exelixis Clinical Site #85; 🇧🇷 São Paulo, Brazil

Exelixis Clinical Site #53; 🇨🇱 Providencia, Chile

Exelixis Clinical Site #61; 🇨🇿 Brno, Czechia

Exelixis Clinical Site #27; 🇨🇿 Praha 4, Czechia

Exelixis Clinical Site #86; 🇨🇿 Praha 5, Czechia

Exelixis Clinical Site #71; 🇫🇮 Helsinki, Finland

Exelixis Clinical Site #74; 🇫🇷 Caen Cedex, France

Exelixis Clinical Site #66; 🇫🇷 Clermont-Ferrand, France

Exelixis Clinical Site #40; 🇫🇷 Creteil, France

Exelixis Clinical Site #38; 🇫🇷 Le Mans, France

Exelixis Clinical Site #36; 🇫🇷 Marseille, France

Exelixis Clinical Site #67; 🇫🇷 Paris Cedex, France

Exelixis Clinical Site #12; 🇫🇷 Paris, France

Exelixis Clinical Site #76; 🇫🇷 Pierre-Bénite, France

Exelixis Clinical Site #59; 🇫🇷 Reims cedex, France

Exelixis Clinical Site #28; 🇫🇷 Rennes, France

Exelixis Clinical Site #41; 🇫🇷 Strasbourg, France

Exelixis Clinical Site #65; 🇫🇷 Suresnes, France

Exelixis Clinical Site #79; 🇩🇪 Lutherstadt Eisleben, Germany

Exelixis Clinical Site #7; 🇮🇹 Arezzo, Italy

Exelixis Clinical Site #26; 🇮🇹 Brescia, Italy

Exelixis Clinical Site #19; 🇮🇹 Meldola, Italy

Exelixis Clinical Site #30; 🇮🇹 Napoli, Italy

Exelixis Clinical Site #37; 🇮🇹 Pavia, Italy

Exelixis Clinical Site #63; 🇮🇹 Pisa, Italy

Exelixis Clinical Site #48; 🇮🇹 Reggio Emilia, Italy

Exelixis Clinical Site #60; 🇮🇹 Roma, Italy

Exelixis Clinical Site #72; 🇮🇹 San Giovanni Rotondo, Italy

Exelixis Clinical Site #17; 🇮🇹 Verona, Italy

Exelixis Clinical Site #11; 🇰🇷 Busan, Korea, Republic of

Exelixis Clinical Site #32; 🇰🇷 Busan, Korea, Republic of

Exelixis Clinical Site #22; 🇰🇷 Daegu, Korea, Republic of

Exelixis Clinical Site #13; 🇰🇷 Daejeon, Korea, Republic of

Exelixis Clinical Site #16; 🇰🇷 Goyang-si, Korea, Republic of

Exelixis Clinical Site #25; 🇰🇷 Gyeonggi-do, Korea, Republic of

Exelixis Clinical Site #21; 🇰🇷 Seongnam-si, Korea, Republic of

Exelixis Clinical Site #5; 🇰🇷 Seongnam-si, Korea, Republic of

Exelixis Clinical Site #10; 🇰🇷 Seoul, Korea, Republic of

Exelixis Clinical Site #4; 🇰🇷 Seoul, Korea, Republic of

Exelixis Clinical Site #47; 🇰🇷 Seoul, Korea, Republic of

Exelixis Clinical Site #6; 🇰🇷 Seoul, Korea, Republic of

Exelixis Clinical Site #20; 🇰🇷 Seoul, Korea, Republic of

Exelixis Clinical Site #54; 🇲🇾 Kuala Lumpur, Malaysia

Exelixis Clinical Site #24; 🇲🇾 Kuala Lumpur, Malaysia

Exelixis Clinical Site #46; 🇲🇾 Putrajaya, Malaysia

Exelixis Clinical Site #64; 🇳🇱 Eindhoven, Netherlands

Exelixis Clinical Site #45; 🇵🇱 Bydgoszcz, Poland

Exelixis Clinical Site #49; 🇵🇱 Gdańsk, Poland

Exelixis Clinical Site #33; 🇵🇱 Otwock, Poland

Exelixis Clinical Site #77; 🇵🇱 Poznań, Poland

Exelixis Clinical Site #80; 🇵🇱 Poznań, Poland

Exelixis Clinical Site #23; 🇵🇱 Rzeszow, Poland

Exelixis Clinical Site #56; 🇪🇸 Barcelona, Spain

Exelixis Clinical Site #9; 🇪🇸 Barcelona, Spain

Exelixis Clinical Site #52; 🇪🇸 Barcelona, Spain

Exelixis Clinical Site #62; 🇪🇸 Girona, Spain

Exelixis Clinical Site #3; 🇪🇸 Madrid, Spain

Exelixis Clinical Site #34; 🇪🇸 Madrid, Spain

Exelixis Clinical Site #8; 🇪🇸 Madrid, Spain

Exelixis Clinical Site #57; 🇪🇸 Oviedo, Spain

Exelixis Clinical Site #75; 🇪🇸 Santander, Spain

Exelixis Clinical Site #18; 🇪🇸 Sevilla, Spain

Exelixis Clinical Site #73; 🇪🇸 Valencia, Spain

Exelixis Clinical Site #84; 🇹🇭 Bangkok, Thailand

Exelixis Clinical Site #83; 🇹🇭 Bangkok, Thailand

Exelixis Clinical Site #82; 🇹🇭 Chiang Mai, Thailand