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

NCT ID: NCT05425940

Last Updated: 2025-10-23

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

ACTIVE_NOT_RECRUITING

Clinical Phase

PHASE3

Total Enrollment

901 participants

Study Classification

INTERVENTIONAL

Study Start Date

2022-09-07

Study Completion Date

2027-01-31

Brief Summary

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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.

Detailed Description

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Conditions

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Colorectal Cancer

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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XL092 + Atezolizumab

Participants with mCRC will receive XL092 + atezolizumab.

Group Type EXPERIMENTAL

XL092

Intervention Type DRUG

Supplied as tablets; administered orally daily.

Atezolizumab

Intervention Type 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).

Regorafenib

Participants with mCRC will receive active comparator of regorafenib.

Group Type ACTIVE_COMPARATOR

Regorafenib

Intervention Type DRUG

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

Interventions

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XL092

Supplied as tablets; administered orally daily.

Intervention Type DRUG

Atezolizumab

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

Intervention Type DRUG

Regorafenib

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

Intervention Type DRUG

Other Intervention Names

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Tecentriq® Stivarga®

Eligibility Criteria

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Inclusion Criteria

* 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.

Exclusion Criteria

* 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.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Exelixis

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Medical Director

Role: STUDY_DIRECTOR

Exelixis

Locations

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Exelixis Clinical Site #65

Jonesboro, Alabama, United States

Site Status

Exelixis Clinical Site #30

Phoenix, Arizona, United States

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Exelixis Clinical Site #70

Tucson, Arizona, United States

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Exelixis Clinical Site #9

Duarte, California, United States

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Exelixis Clinical Site #55

La Jolla, California, United States

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Exelixis Clinical Site #77

Los Angeles, California, United States

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Exelixis Clinical Site #105

Orange, California, United States

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Exelixis Clinical Site #80

Santa Monica, California, United States

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Exelixis Clinical Site #5

Santa Rosa, California, United States

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Exelixis Clinical Site #82

Sylmar, California, United States

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Exelixis Clinical Site #58

Torrance, California, United States

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Exelixis Clinical Site #81

Whittier, California, United States

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Exelixis Clinical Site #125

New Haven, Connecticut, United States

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Exelixis Clinical Site #16

Miami Beach, Florida, United States

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Exelixis Clinical Site #60

Orlando, Florida, United States

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Exelixis Clinical Site #4

Marietta, Georgia, United States

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Exelixis Clinical Site #3

Joliet, Illinois, United States

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Exelixis Clinical Site #102

Indianapolis, Indiana, United States

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Exelixis Clinical Site #10

Westwood, Kansas, United States

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Exelixis Clinical Site #47

Lexington, Kentucky, United States

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Exelixis Clinical Site #7

New Orleans, Louisiana, United States

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Exelixis Clinical Site #22

St Louis, Missouri, United States

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Exelixis Clinical Site #8

Billings, Montana, United States

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Exelixis Clinical Site #1

Omaha, Nebraska, United States

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Exelixis Clinical Site #15

Albuquerque, New Mexico, United States

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Exelixis Clinical Site #11

New York, New York, United States

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Exelixis Clinical Site #59

New York, New York, United States

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Exelixis Clinical Site #17

The Bronx, New York, United States

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Exelixis Clinical Site #74

Charlotte, North Carolina, United States

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Exelixis Clinical Site #6

Cincinnati, Ohio, United States

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Exelixis Clinical Site #12

Oklahoma City, Oklahoma, United States

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Exelixis Clinical Site #75

Portland, Oregon, United States

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Exelixis Clinical Site #106

Philadelphia, Pennsylvania, United States

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Exelixis Clinical Site #18

Pittsburgh, Pennsylvania, United States

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Exelixis Clinical Site #103

Pittsburgh, Pennsylvania, United States

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Exelixis Clinical Site #24

Greenville, South Carolina, United States

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Exelixis Clinical Site #56

Chattanooga, Tennessee, United States

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Exelixis Clinical Site #76

Nashville, Tennessee, United States

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Exelixis Clinical Site #133

Nashville, Tennessee, United States

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Exelixis Clinical Site #450

Fairfax, Virginia, United States

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Exelixis Clinical Site #14

Roanoke, Virginia, United States

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Exelixis Clinical Site #13

Seattle, Washington, United States

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Exelixis Clinical Site #32

Seattle, Washington, United States

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Exelixis Clinical Site #89

Seattle, Washington, United States

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Exelixis Clinical Site #2

Spokane, Washington, United States

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Exelixis Clinical Site #83

Albury, , Australia

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Exelixis Clinical Site #53

Bankstown, , Australia

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Exelixis Clinical Site #117

Bedford Park, , Australia

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Exelixis Clinical Site #97

Heidelberg, , Australia

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Exelixis Clinical Site #19

Melbourne, , Australia

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Exelixis Clinical Site #23

Melbourne, , Australia

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Exelixis Clinical Site #27

Port Macquarie, , Australia

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Exelixis Clinical Site #64

Woodville South, , Australia

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Exelixis Clinical Site #43

Antwerp, , Belgium

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Exelixis Clinical Site #51

Brussels, , Belgium

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Exelixis Clinical Site #35

Namur, , Belgium

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Exelixis Clinical Site #52

Besançon, , France

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Exelixis Clinical Site #84

Dijon, , France

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Exelixis Clinical Site #88

Herbault, , France

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Exelixis Clinical Site #71

Lyon, , France

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Exelixis Clinical Site #87

Marseille, , France

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Exelixis Clinical Site #38

Paris, , France

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Exelixis Clinical Site #93

Suresnes, , France

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Exelixis Clinical Site #127

Hanover, Niedersach, Germany

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Exelixis Clinical Site #109

Dresden, , Germany

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Exelixis Clinical Site #113

Frankfurt am Main, , Germany

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Exelixis Clinical Site #61

Hamburg, , Germany

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Exelixis Clinical Site #63

Hamburg, , Germany

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Exelixis Clinical Site #91

München, , 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, Hungary

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Exelixis Clinical Site #41

Budapest, , Hungary

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Exelixis Clinical Site #129

Budapest, , Hungary

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Exelixis Clinical Site #48

Debrecen, , Hungary

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Exelixis Clinical Site #122

Győr, , Hungary

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Exelixis Clinical Site #57

Auckland, , New Zealand

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Exelixis Clinical Site #49

Dunedin, , New Zealand

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Exelixis Clinical Site #69

Hamilton, , New Zealand

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Exelixis Clinical Site #104

Wellington, , New Zealand

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Exelixis Clinical Site #20

Bydgoszcz, , Poland

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Exelixis Clinical Site #68

Opole, , Poland

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Exelixis Clinical Site #26

Siedlce, , Poland

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Exelixis Clinical Site #42

Tomaszów Mazowiecki, , Poland

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Exelixis Clinical Site #31

Warsaw, , Poland

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Exelixis Clinical Site #108

Almada, , Portugal

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Exelixis Clinical Site #120

Coimbra, , Portugal

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Exelixis Clinical Site #99

Guimarães, , Portugal

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Exelixis Clinical Site #131

Lisbon, , Portugal

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Exelixis Clinical Site #124

Lisbon, , Portugal

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Exelixis Clinical Site #96

Lisbon, , Portugal

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Exelixis Clinical Site #132

Singapore, , Singapore

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Exelixis Clinical Site #100

Singapore, , Singapore

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Exelixis Clinical Site #39

Singapore, , Singapore

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Exelixis Clinical Site #98

Singapore, , Singapore

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Exelixis Clinical Site #94

Singapore, , Singapore

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Exelixis Clinical Site #36

Goyang-si, , South Korea

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Exelixis Clinical Site #29

Gyeonggi-do, , South Korea

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Exelixis Clinical Site #28

Hwasun, , South Korea

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Exelixis Clinical Site #37

Seongnam-si, , South Korea

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Exelixis Clinical Site #34

Seoul, , South Korea

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Exelixis Clinical Site #45

Seoul, , South Korea

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Exelixis Clinical Site #66

Seoul, , South Korea

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Exelixis Clinical Site #46

Seoul, , South Korea

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Exelixis Clinical Site #54

Seoul, , South Korea

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Exelixis Clinical Site #44

Seoul, , South Korea

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Exelixis Clinical Site #40

Seoul, , South Korea

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Exelixis Clinical Site #78

Barcelona, , Spain

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Exelixis Clinical Site #21

Barcelona, , Spain

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Exelixis Clinical Site #86

Barcelona, , Spain

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Exelixis Clinical Site #112

Barcelona, , Spain

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Exelixis Clinical Site #95

Lleida, , Spain

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Exelixis Clinical Site #116

Madrid, , Spain

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Exelixis Clinical Site #72

Madrid, , Spain

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Exelixis Clinical Site #67

Madrid, , Spain

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Exelixis Clinical Site #79

Madrid, , Spain

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Exelixis Clinical Site #90

Valencia, , Spain

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Exelixis Clinical Site #121

Zaragoza, , Spain

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Exelixis Clinical Site #119

Guishan, , Taiwan

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Exelixis Clinical Site #85

Kaohsiung City, , Taiwan

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Exelixis Clinical Site #107

Kaohsiung City, , Taiwan

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Exelixis Clinical Site #118

Liuying, , Taiwan

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Exelixis Clinical Site #73

Taichung, , Taiwan

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Exelixis Clinical Site #101

Tainan City, , Taiwan

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Exelixis Clinical Site #62

Chiang Mai, , Thailand

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Exelixis Clinical Site #92

Hat Yai, , Thailand

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Exelixis Clinical Site #130

Bristol, England, United Kingdom

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Exelixis Clinical Site #110

Birmingham, , United Kingdom

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Exelixis Clinical Site #111

Edinburgh, , United Kingdom

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Exelixis Clinical Site #123

London, , United Kingdom

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Exelixis Clinical Site #114

London, , United Kingdom

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Exelixis Clinical Site #115

Romford, , United Kingdom

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Exelixis Clinical Site #126

Sutton, , United Kingdom

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Countries

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United States Australia Belgium France Germany Hong Kong Hungary New Zealand Poland Portugal Singapore South Korea Spain Taiwan Thailand United Kingdom

References

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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 Oct 20:S0140-6736(25)02025-2. doi: 10.1016/S0140-6736(25)02025-2. Online ahead of print.

Reference Type DERIVED
PMID: 41130252 (View on PubMed)

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.

Reference Type DERIVED
PMID: 39041200 (View on PubMed)

Other Identifiers

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2021-003243-21

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

XL092-303

Identifier Type: -

Identifier Source: org_study_id

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