Study of XL092 + Atezolizumab vs Regorafenib in Participants With Metastatic Colorectal Cancer

NCT05425940 | Active Not Recruiting Phase 3 DMC FDA Drug

• 2 other identifiers: XL092-3032021-003243-21
• Study Type: interventional
• Target: 901
• Locations: 16 countries
• Sites: 133

Brief Summary

The primary purpose of this study is to evaluate XL092 + atezolizumab versus regorafenib in participants with microsatellite stable/microsatellite instability low (MSS/MSI-low) metastatic colorectal cancer (mCRC) who have progressed during, after or are intolerant to standard-of-care (SOC) therapy.

Conditions

Colorectal Cancer

Keywords

Colorectal Cancer

Outcome Measures

Primary Outcomes (2)

• Overall Survival (OS) of XL092 + Atezolizumab Versus Regorafenib in All Randomized Participants

  Up to 32 months

• Overall Survival (OS) of XL092 + Atezolizumab Versus Regorafenib in Randomized Non-Liver Metastases (NLM) Participants

  Up to 32 months

Secondary Outcomes (7)

• Progression-Free Survival (PFS) as Assessed by the Investigator

  Up to 26 months

• Duration of Response (DOR) as Assessed by the Investigator

  Up to 36 months

• Objective Response Rate (ORR) as Assessed by the Investigator

  Up to 36 months

• Number of Participants with Treatment Emergent Adverse Events (TEAEs)

  Up to 36 months

• Maximum Observed Plasma Drug Concentration (Cmax) of XL092

  Predose up to 72 hours postdose

Study Arms (2)

XL092 + Atezolizumab

EXPERIMENTAL

Participants with mCRC will receive XL092 + atezolizumab.

Drug: XL092; Drug: Atezolizumab

Regorafenib

ACTIVE COMPARATOR

Participants with mCRC will receive active comparator of regorafenib.

Drug: Regorafenib

Interventions

XL092 DRUG

Supplied as tablets; administered orally daily.

XL092 + Atezolizumab

Atezolizumab DRUG

Supplied as 1200 milligrams (mg)/20 milliliter (mL) vials; administered as a 1200 mg intravenous (IV) infusion once in a 3-week cycle (q3w).

Also known as: Tecentriq®

XL092 + Atezolizumab

Regorafenib DRUG

Supplied as 40 mg tablets; administered orally daily at 160 mg for the first 21 days of each 28-day cycle.

Also known as: Stivarga®

Regorafenib

Eligibility Criteria

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

You may qualify if:

• Participants with histologically or cytologically confirmed adenocarcinoma of the colon or rectum.
• Documented rat sarcoma (RAS) status (mutant or wild-type \[WT\]), by tissue-based analysis.
• Documented NOT to have microsatellite instability-high (MSI-high) or mismatch repair deficient (dMMR) CRC by tissue-based analysis.
• Has received SOC anticancer therapies as prior therapy for metastatic CRC and has radiographically progressed, is refractory or intolerant to these therapies.
• Systemic SOC anticancer therapy if approved and available in the country where the participant is randomized.
• Radiographic progression during treatment with or within 4 months following the last dose of the most recent approved SOC chemotherapy regimen.
• Measurable disease according to Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 as determined by the Investigator.
• Available archival tumor biopsy material. If archival tissue is unavailable, must provide fresh tumor tissue biopsy prior to randomization.
• Recovery to baseline or ≤ Grade 1 severity (common terminology criteria for adverse events \[CTCAE\] version 5) from adverse events (AEs) related to any prior treatments, unless AE(s) are clinically nonsignificant and/or stable on supportive therapy.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0-1.
• Adequate organ and marrow function.
• Fertile participants and their partners must agree to use highly effective methods of contraception during the course of the study and after the last dose of treatment.
• Females of childbearing potential must not be pregnant at screening.

You may not qualify if:

• Prior treatment with XL092, regorafenib, trifluridine/tipiracil, or programmed cell death protein-1/and its ligand (PD-L1/PD-1) targeting immune checkpoint inhibitors (ICIs).
• Receipt of a small molecule kinase inhibitor (including investigational agents) within 2 weeks before randomization.
• Receipt of any type of anticancer antibody therapy, systemic chemotherapy, or hormonal anti-cancer therapy within 3 weeks (or bevacizumab within 4 weeks) before randomization.
• Radiation therapy for bone metastasis within 2 weeks, any other radiation therapy within 4 weeks before randomization.
• Known brain metastases or cranial epidural disease unless adequately treated with radiotherapy and/or surgery (including radiosurgery) and stable for at least 4 weeks before randomization.
• Has uncontrolled, significant intercurrent or recent illness.
• Major surgery (example, gastrointestinal (GI) surgery, removal or biopsy of brain metastasis) within 4 weeks prior to randomization.
• Systemic treatment with, or any condition requiring, either corticosteroids (\> 10 mg daily prednisone equivalent) or other immunosuppressive medications within 14 days prior to randomization.
• Corrected QT interval calculated by the Fridericia formula (QTcF) \> 460 milliseconds (ms) within 10 days before randomization.
• History of psychiatric illness likely to interfere with ability to comply with protocol requirements or give informed consent.
• Pregnant or lactating females.
• Inability to swallow study treatment formulation, inability to receive IV administration, or presence of GI condition that might affect the absorption of study drug.
• Previously identified allergy or hypersensitivity to components of the study treatment formulations.
• Any other active malignancy or diagnosis of another malignancy within 2 years before randomization. Exceptions are noted in the protocol.
• Administration of a live, attenuated vaccine within 30 days before randomization.

Sponsors & Collaborators

• Exelixis: lead

Study Sites (133)

Exelixis Clinical Site #65

Jonesboro, Alabama, 72401, United States

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Exelixis Clinical Site #30

Phoenix, Arizona, 85004, United States

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Exelixis Clinical Site #70

Tucson, Arizona, 85719, United States

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Exelixis Clinical Site #9

Duarte, California, 91010, United States

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Exelixis Clinical Site #55

La Jolla, California, 92037, United States

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Exelixis Clinical Site #77

Los Angeles, California, 90095, United States

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Exelixis Clinical Site #105

Orange, California, 92868, United States

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Exelixis Clinical Site #80

Santa Monica, California, 90404, United States

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Exelixis Clinical Site #5

Santa Rosa, California, 95403, United States

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Exelixis Clinical Site #82

Sylmar, California, 91342, United States

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Exelixis Clinical Site #58

Torrance, California, 90505, United States

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Exelixis Clinical Site #81

Whittier, California, 90602, United States

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Exelixis Clinical Site #125

New Haven, Connecticut, 06510, United States

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Exelixis Clinical Site #16

Miami Beach, Florida, 33140, United States

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Exelixis Clinical Site #60

Orlando, Florida, 32804, United States

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Exelixis Clinical Site #4

Marietta, Georgia, 30060, United States

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Exelixis Clinical Site #3

Joliet, Illinois, 60435, United States

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Exelixis Clinical Site #102

Indianapolis, Indiana, 46250, United States

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Exelixis Clinical Site #10

Westwood, Kansas, 66205, United States

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Exelixis Clinical Site #47

Lexington, Kentucky, 40536, United States

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Exelixis Clinical Site #7

New Orleans, Louisiana, 70112, United States

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Exelixis Clinical Site #22

St Louis, Missouri, 63141, United States

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Exelixis Clinical Site #8

Billings, Montana, 59102, United States

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Exelixis Clinical Site #1

Omaha, Nebraska, 68130, United States

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Exelixis Clinical Site #15

Albuquerque, New Mexico, 87131, United States

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Exelixis Clinical Site #11

New York, New York, 10016, United States

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Exelixis Clinical Site #59

New York, New York, 10029, United States

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Exelixis Clinical Site #17

The Bronx, New York, 10461, United States

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Exelixis Clinical Site #74

Charlotte, North Carolina, 28204, United States

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Exelixis Clinical Site #6

Cincinnati, Ohio, 45219, United States

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Exelixis Clinical Site #12

Oklahoma City, Oklahoma, 73142, United States

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Exelixis Clinical Site #75

Portland, Oregon, 97210, United States

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Exelixis Clinical Site #106

Philadelphia, Pennsylvania, 19107, United States

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Exelixis Clinical Site #18

Pittsburgh, Pennsylvania, 15212, United States

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Exelixis Clinical Site #103

Pittsburgh, Pennsylvania, 15232, United States

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Exelixis Clinical Site #24

Greenville, South Carolina, 29607, United States

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Exelixis Clinical Site #56

Chattanooga, Tennessee, 37404, United States

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Exelixis Clinical Site #76

Nashville, Tennessee, 37203, United States

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Exelixis Clinical Site #133

Nashville, Tennessee, 37232, United States

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Exelixis Clinical Site #450

Fairfax, Virginia, 22031, United States

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Exelixis Clinical Site #14

Roanoke, Virginia, 24014, United States

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Exelixis Clinical Site #13

Seattle, Washington, 98101, United States

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Exelixis Clinical Site #32

Seattle, Washington, 98104, United States

Location

Exelixis Clinical Site #89

Seattle, Washington, 98109, United States

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Exelixis Clinical Site #2

Spokane, Washington, 99208, United States

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Exelixis Clinical Site #83

Albury, 2640, Australia

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Exelixis Clinical Site #53

Bankstown, 2200, Australia

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Exelixis Clinical Site #117

Bedford Park, 5042, Australia

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Exelixis Clinical Site #97

Heidelberg, 3084, Australia

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Exelixis Clinical Site #19

Melbourne, 3002, Australia

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Exelixis Clinical Site #23

Melbourne, 3021, Australia

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Exelixis Clinical Site #27

Port Macquarie, 2444, Australia

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Exelixis Clinical Site #64

Woodville South, 5011, Australia

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Exelixis Clinical Site #43

Antwerp, 2300, Belgium

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Exelixis Clinical Site #51

Brussels, 1200, Belgium

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Exelixis Clinical Site #35

Namur, 5000, Belgium

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Exelixis Clinical Site #52

Besançon, 25030, France

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Exelixis Clinical Site #84

Dijon, 21079, France

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Exelixis Clinical Site #88

Herbault, 34298, France

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Exelixis Clinical Site #71

Lyon, 69008, France

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Exelixis Clinical Site #87

Marseille, 13385, France

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Exelixis Clinical Site #38

Paris, 75020, France

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Exelixis Clinical Site #93

Suresnes, 92150, France

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Exelixis Clinical Site #127

Hanover, Niedersach, 30625, Germany

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Exelixis Clinical Site #109

Dresden, 01307, Germany

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Exelixis Clinical Site #113

Frankfurt am Main, 60488, Germany

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Exelixis Clinical Site #61

Hamburg, 20249, Germany

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Exelixis Clinical Site #63

Hamburg, 22763, Germany

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Exelixis Clinical Site #91

München, 81737, Germany

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Exelixis Clinical Site #25

Hong Kong, Hong Kong

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Exelixis Clinical Site #33

Hong Kong, Hong Kong

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Exelixis Clinical Site #128

Nyíregyháza, Szabolcs-Szatmar-Bereg County, 4400, Hungary

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Exelixis Clinical Site #41

Budapest, 1097, Hungary

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Exelixis Clinical Site #129

Budapest, 1122, Hungary

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Exelixis Clinical Site #48

Debrecen, 4302, Hungary

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Exelixis Clinical Site #122

Győr, 9024, Hungary

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Exelixis Clinical Site #57

Auckland, 1023, New Zealand

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Exelixis Clinical Site #49

Dunedin, 9016, New Zealand

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Exelixis Clinical Site #69

Hamilton, 3204, New Zealand

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Exelixis Clinical Site #104

Wellington, 6021, New Zealand

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Exelixis Clinical Site #20

Bydgoszcz, 85-796, Poland

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Exelixis Clinical Site #68

Opole, 45-061, Poland

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Exelixis Clinical Site #26

Siedlce, 08-110, Poland

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Exelixis Clinical Site #42

Tomaszów Mazowiecki, 97-200, Poland

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Exelixis Clinical Site #31

Warsaw, 02-507, Poland

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Exelixis Clinical Site #108

Almada, 2805-267, Portugal

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Exelixis Clinical Site #120

Coimbra, 3000-075, Portugal

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Exelixis Clinical Site #99

Guimarães, 4835-044, Portugal

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Exelixis Clinical Site #131

Lisbon, 1500-650, Portugal

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Exelixis Clinical Site #124

Lisbon, 1649-035, Portugal

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Exelixis Clinical Site #96

Lisbon, 400-038, Portugal

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Exelixis Clinical Site #132

Singapore, 119228, Singapore

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Exelixis Clinical Site #100

Singapore, 168583, Singapore

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Exelixis Clinical Site #39

Singapore, 217562, Singapore

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Exelixis Clinical Site #98

Singapore, 258499, Singapore

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Exelixis Clinical Site #94

Singapore, 329563, Singapore

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Exelixis Clinical Site #36

Goyang-si, 10408, South Korea

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Exelixis Clinical Site #29

Gyeonggi-do, 14068, South Korea

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Exelixis Clinical Site #28

Hwasun, 58128, South Korea

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Exelixis Clinical Site #37

Seongnam-si, 13620, South Korea

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Exelixis Clinical Site #34

Seoul, 03080, South Korea

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Exelixis Clinical Site #45

Seoul, 03722, South Korea

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Exelixis Clinical Site #66

Seoul, 05505, South Korea

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Exelixis Clinical Site #46

Seoul, 06351, South Korea

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Exelixis Clinical Site #54

Seoul, 06591, South Korea

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Exelixis Clinical Site #44

Seoul, 08308, South Korea

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Exelixis Clinical Site #40

Seoul, South Korea

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Exelixis Clinical Site #78

Barcelona, 08023, Spain

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Exelixis Clinical Site #21

Barcelona, 08025, Spain

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Exelixis Clinical Site #86

Barcelona, 08035, Spain

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Exelixis Clinical Site #112

Barcelona, 08908, Spain

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Exelixis Clinical Site #95

Lleida, 25198, Spain

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Exelixis Clinical Site #116

Madrid, 28007, Spain

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Exelixis Clinical Site #72

Madrid, 28034, Spain

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Exelixis Clinical Site #67

Madrid, 28041, Spain

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Exelixis Clinical Site #79

Madrid, 28050, Spain

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Exelixis Clinical Site #90

Valencia, 46014, Spain

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Exelixis Clinical Site #121

Zaragoza, 50009, Spain

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Exelixis Clinical Site #119

Guishan, 333, Taiwan

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Exelixis Clinical Site #85

Kaohsiung City, 807, Taiwan

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Exelixis Clinical Site #107

Kaohsiung City, 833, Taiwan

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Exelixis Clinical Site #118

Liuying, 73657, Taiwan

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Exelixis Clinical Site #73

Taichung, 40447, Taiwan

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Exelixis Clinical Site #101

Tainan, 704, Taiwan

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Exelixis Clinical Site #62

Chiang Mai, 50200, Thailand

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Exelixis Clinical Site #92

Hat Yai, 90110, Thailand

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Exelixis Clinical Site #130

Bristol, England, BS2 8ED, United Kingdom

Location

Exelixis Clinical Site #110

Birmingham, B95SS, United Kingdom

Location

Exelixis Clinical Site #111

Edinburgh, EH42XU, United Kingdom

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Exelixis Clinical Site #123

London, EC1A 7BE, United Kingdom

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Exelixis Clinical Site #114

London, W1G 6AD, United Kingdom

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Exelixis Clinical Site #115

Romford, RM70AG, United Kingdom

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Exelixis Clinical Site #126

Sutton, SM2 5PT, United Kingdom

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Related Publications (2)

• Hecht JR, Park YS, Tabernero J, Lee MA, Lee S, Virgili AC, Van den Eynde M, Fontana E, Fakih M, Asghari G, So J, Stein A, Dubreuil O, Bodnar L, He CS, Wang G, Smith R, Eng C, Saeed A; STELLAR-303 study investigators. Zanzalintinib plus atezolizumab versus regorafenib in refractory colorectal cancer (STELLAR-303): a randomised, open-label, phase 3 trial. Lancet. 2025 Nov 15;406(10517):2360-2370. doi: 10.1016/S0140-6736(25)02025-2. Epub 2025 Oct 20.

  PMID: 41130252 DERIVED

• Saeed A, Tabernero J, Parikh A, Van den Eynde M, Karthaus M, Gerlinger M, Wang Z, Wang G, Smith R, Hecht JR. STELLAR-303: randomized phase III study of zanzalintinib + atezolizumab in previously treated metastatic colorectal cancer. Future Oncol. 2024;20(24):1733-1743. doi: 10.1080/14796694.2024.2352276. Epub 2024 Jul 23.

  PMID: 39041200 DERIVED

MeSH Terms

Conditions

Colorectal Neoplasms

Interventions

atezolizumab; regorafenib

Condition Hierarchy (Ancestors)

Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases

Study Officials

• Medical Director

  Exelixis

  STUDY DIRECTOR

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: June 16, 2022
• First Posted: June 21, 2022
• Study Start: September 7, 2022
• Primary Completion: May 1, 2026
• Study Completion (Estimated): January 1, 2027
• Last Updated: October 23, 2025

Record last verified: 2025-10

Data Sharing

• IPD Sharing: Will not share

Locations

BE (3); KR (11); GB (7); HK (2); HU (5); SG (5); US (45); FR (7); TH (2); TW (6); NZ (4); PL (5); AU (8); DE (6); ES (11); PT (6)