Study of XL092 + Atezolizumab vs Regorafenib in Subjects With Metastatic Colorectal Cancer
- Conditions
- Colorectal Cancer
- Interventions
- Registration Number
- NCT05425940
- Lead Sponsor
- Exelixis
- Brief Summary
This is a multicenter, randomized, open-label, controlled Phase 3 trial of XL092 + atezolizumab vs regorafenib in subjects 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
Not available
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- All
- Target Recruitment
- 874
-
Subjects with histologically or cytologically confirmed adenocarcinoma of the colon or rectum.
- Documented 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 standard-of-care (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 subject 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 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 (CTCAE v5) from adverse events (AEs) related to any prior treatments, unless AE(s) are clinically nonsignificant and/or stable on supportive therapy.
-
Age 18 years or older on the day of consent.
-
Eastern Cooperative Oncology Group (ECOG) performance status of 0-1.
-
Adequate organ and marrow function.
-
Fertile subjects 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.
-
Female subjects of childbearing potential must not be pregnant at screening.
- Prior treatment with XL092, regorafenib, trifluridine/tipiracil, or 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.
- Subject has uncontrolled, significant intercurrent or recent illness.
- Major surgery (e.g., 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 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.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Experimental Arm XL092 Subjects with mCRC will receive XL092 + atezolizumab Control Arm Regorafenib Subjects with mCRC will receive active comparator of regorafenib Experimental Arm Atezolizumab Subjects with mCRC will receive XL092 + atezolizumab
- Primary Outcome Measures
Name Time Method Overall Survival Approximately 32 months after the first subject is randomized. The primary objective of this study is to evaluate OS of XL092 + atezolizumab versus regorafenib in non-liver metastases (NLM) subjects with MSS/MSI-low mCRC who have progressed during, after, or are intolerant to SOC therapy.
Subjects without liver metastases (NLM) are defined as subjects without active liver metastases at screening as determined on baseline imaging of the liver as performed by CT scan with contrast or MRI.
Definitively treated liver metastases (which includes surgical resection, microwave or radiofrequency ablation, or stereotactic body radiation therapy, but not yttrium-90 or chemoembolization alone) that were treated at least 6 months prior to enrollment with no evidence of radiologic progression on subsequent imaging are considered to be non-active liver metastases.
- Secondary Outcome Measures
Name Time Method Overall Survival Approximately 32 months after the first subject is randomized. The key secondary objective is to evaluate OS of XL092 + atezolizumab versus regorafenib in all randomized subjects with MSS/MSI-low mCRC who have progressed during, after, or are intolerant to SOC therapy.
Trial Locations
- Locations (133)
Exelixis Clinical Site #77
🇺🇸Los Angeles, California, United States
Exelixis Clinical Site #106
🇺🇸Philadelphia, Pennsylvania, United States
Exelixis Clinical Site #103
🇺🇸Pittsburgh, Pennsylvania, United States
Exelixis Clinical Site #30
🇺🇸Phoenix, Arizona, United States
Exelixis Clinical Site #102
🇺🇸Indianapolis, Indiana, United States
Exelixis Clinical Site #6
🇺🇸Cincinnati, Ohio, United States
Exelixis Clinical Site #133
🇺🇸Nashville, Tennessee, United States
Exelixis Clinical Site #89
🇺🇸Seattle, Washington, United States
Exelixis Clinical Site #108
🇵🇹Almada, Portugal
Exelixis Clinical Site #8
🇺🇸Billings, Montana, United States
Exelixis Clinical Site #124
🇵🇹Lisboa, Portugal
Exelixis Clinical Site #62
🇹🇭Chiang Mai, Thailand
Exelixis Clinical Site #120
🇵🇹Coimbra, Portugal
Exelixis Clinical Site #84
🇫🇷Dijon, France
Exelixis Clinical Site #65
🇺🇸Jonesboro, Alabama, United States
Exelixis Clinical Site #70
🇺🇸Tucson, Arizona, United States
Exelixis Clinical Site #80
🇺🇸Santa Monica, California, United States
Exelixis Clinical Site #105
🇺🇸Orange, California, United States
Exelixis Clinical Site #5
🇺🇸Santa Rosa, California, United States
Exelixis Clinical Site #58
🇺🇸Torrance, California, United States
Exelixis Clinical Site #16
🇺🇸Miami Beach, Florida, United States
Exelixis Clinical Site #22
🇺🇸Saint Louis, Missouri, United States
Exelixis Clinical Site #10
🇺🇸Westwood, Kansas, United States
Exelixis Clinical Site #47
🇺🇸Lexington, Kentucky, United States
Exelixis Clinical Site #7
🇺🇸New Orleans, Louisiana, United States
Exelixis Clinical Site #15
🇺🇸Albuquerque, New Mexico, United States
Exelixis Clinical Site #59
🇺🇸New York, New York, United States
Exelixis Clinical Site #11
🇺🇸New York, New York, United States
Exelixis Clinical Site #74
🇺🇸Charlotte, North Carolina, United States
Exelixis Clinical Site #56
🇺🇸Chattanooga, Tennessee, United States
Exelixis Clinical Site #76
🇺🇸Nashville, Tennessee, United States
Exelixis Clinical Site #450
🇺🇸Fairfax, Virginia, United States
Exelixis Clinical Site #13
🇺🇸Seattle, Washington, United States
Exelixis Clinical Site #14
🇺🇸Roanoke, Virginia, United States
Exelixis Clinical Site #83
🇦🇺Albury, Australia
Exelixis Clinical Site #53
🇦🇺Bankstown, Australia
Exelixis Clinical Site #117
🇦🇺Bedford Park, Australia
Exelixis Clinical Site #19
🇦🇺Melbourne, Australia
Exelixis Clinical Site #64
🇦🇺Woodville South, Australia
Exelixis Clinical Site #97
🇦🇺Heidelberg, Australia
Exelixis Clinical Site #43
🇧🇪Antwerp, Belgium
Exelixis Clinical Site #51
🇧🇪Brussels, Belgium
Exelixis Clinical Site #35
🇧🇪Namur, Belgium
Exelixis Clinical Site #52
🇫🇷Besançon, France
Exelixis Clinical Site #38
🇫🇷Paris, France
Exelixis Clinical Site #93
🇫🇷Suresnes, France
Exelixis Clinical Site #113
🇩🇪Frankfurt am Main, Germany
Exelixis Clinical Site #61
🇩🇪Hamburg, Germany
Exelixis Clinical Site #91
🇩🇪München, Germany
Exelixis Clinical Site #41
🇭🇺Budapest, Hungary
Exelixis Clinical Site #122
🇭🇺Győr, Hungary
Exelixis Clinical Site #129
🇭🇺Budapest, Hungary
Exelixis Clinical Site #48
🇭🇺Debrecen, Hungary
Exelixis Clinical Site #36
🇰🇷Goyang-si, Korea, Republic of
Exelixis Clinical Site #34
🇰🇷Seoul, Korea, Republic of
Exelixis Clinical Site #28
🇰🇷Hwasun, Korea, Republic of
Exelixis Clinical Site #45
🇰🇷Seoul, Korea, Republic of
Exelixis Clinical Site #66
🇰🇷Seoul, Korea, Republic of
Exelixis Clinical Site #104
🇳🇿Wellington, New Zealand
Exelixis Clinical Site #20
🇵🇱Bydgoszcz, Poland
Exelixis Clinical Site #26
🇵🇱Siedlce, Poland
Exelixis Clinical Site #68
🇵🇱Opole, Poland
Exelixis Clinical Site #42
🇵🇱Tomaszów Mazowiecki, Poland
Exelixis Clinical Site #131
🇵🇹Lisboa, Portugal
Exelixis Clinical Site #31
🇵🇱Warszawa, Poland
Exelixis Clinical Site #96
🇵🇹Lisboa, Portugal
Exelixis Clinical Site #99
🇵🇹Guimarães, Portugal
Exelixis Clinical Site #21
🇪🇸Barcelona, Spain
Exelixis Clinical Site #132
🇸🇬Singapore, Singapore
Exelixis Clinical Site #94
🇸🇬Singapore, Singapore
Exelixis Clinical Site #78
🇪🇸Barcelona, Spain
Exelixis Clinical Site #39
🇸🇬Singapore, Singapore
Exelixis Clinical Site #98
🇸🇬Singapore, Singapore
Exelixis Clinical Site #100
🇸🇬Singapore, Singapore
Exelixis Clinical Site #86
🇪🇸Barcelona, Spain
Exelixis Clinical Site #95
🇪🇸Lleida, Spain
Exelixis Clinical Site #112
🇪🇸Barcelona, Spain
Exelixis Clinical Site #116
🇪🇸Madrid, Spain
Exelixis Clinical Site #67
🇪🇸Madrid, Spain
Exelixis Clinical Site #79
🇪🇸Madrid, Spain
Exelixis Clinical Site #90
🇪🇸Valencia, Spain
Exelixis Clinical Site #121
🇪🇸Zaragoza, Spain
Exelixis Clinical Site #119
🇨🇳Guishan, Taiwan
Exelixis Clinical Site #107
🇨🇳Kaohsiung, Taiwan
Exelixis Clinical Site #85
🇨🇳Kaohsiung, Taiwan
Exelixis Clinical Site #118
🇨🇳Liuying, Taiwan
Exelixis Clinical Site #101
🇨🇳Tainan, Taiwan
Exelixis Clinical Site #73
🇨🇳Taichung, Taiwan
Exelixis Clinical Site #92
🇹🇭Hat Yai, Thailand
Exelixis Clinical Site #110
🇬🇧Birmingham, United Kingdom
Exelixis Clinical Site #130
🇬🇧Bristol, England, United Kingdom
Exelixis Clinical Site #123
🇬🇧London, United Kingdom
Exelixis Clinical Site #111
🇬🇧Edinburgh, United Kingdom
Exelixis Clinical Site #114
🇬🇧London, United Kingdom
Exelixis Clinical Site #115
🇬🇧Romford, United Kingdom
Exelixis Clinical Site #126
🇬🇧Sutton, United Kingdom
Exelixis Clinical Site #9
🇺🇸Duarte, California, United States
Exelixis Clinical Site #55
🇺🇸La Jolla, California, United States
Exelixis Clinical Site #82
🇺🇸Sylmar, California, United States
Exelixis Clinical Site #81
🇺🇸Whittier, California, United States
Exelixis Clinical Site #4
🇺🇸Marietta, Georgia, United States
Exelixis Clinical Site #3
🇺🇸Joliet, Illinois, United States
Exelixis Clinical Site #17
🇺🇸Bronx, New York, United States
Exelixis Clinical Site #12
🇺🇸Oklahoma City, Oklahoma, United States
Exelixis Clinical Site #18
🇺🇸Pittsburgh, Pennsylvania, United States
Exelixis Clinical Site #24
🇺🇸Greenville, South Carolina, United States
Exelixis Clinical Site #32
🇺🇸Seattle, Washington, United States
Exelixis Clinical Site #2
🇺🇸Spokane, Washington, United States
Exelixis Clinical Site #23
🇦🇺Melbourne, Australia
Exelixis Clinical Site #27
🇦🇺Port Macquarie, Australia
Exelixis Clinical Site #71
🇫🇷Lyon, France
Exelixis Clinical Site #109
🇩🇪Dresden, Germany
Exelixis Clinical Site #127
🇩🇪Hannover, Niedersach, Germany
Exelixis Clinical Site #63
🇩🇪Hamburg, Germany
Exelixis Clinical Site #128
🇭🇺Nyíregyháza, Szabolcs-Szatmar-Bereg County, Hungary
Exelixis Clinical Site #29
🇰🇷Gyeonggi-do, Korea, Republic of
Exelixis Clinical Site #37
🇰🇷Seongnam-si, Korea, Republic of
Exelixis Clinical Site #46
🇰🇷Seoul, Korea, Republic of
Exelixis Clinical Site #44
🇰🇷Seoul, Korea, Republic of
Exelixis Clinical Site #54
🇰🇷Seoul, Korea, Republic of
Exelixis Clinical Site #57
🇳🇿Auckland, New Zealand
Exelixis Clinical Site #40
🇰🇷Seoul, Korea, Republic of
Exelixis Clinical Site #49
🇳🇿Dunedin, New Zealand
Exelixis Clinical Site #69
🇳🇿Hamilton, New Zealand
Exelixis Clinical Site #87
🇫🇷Marseille, France
Exelixis Clinical Site #88
🇫🇷Herbault, France
Exelixis Clinical Site #72
🇪🇸Madrid, Spain
Exelixis Clinical Site #125
🇺🇸New Haven, Connecticut, United States
Exelixis Clinical Site #1
🇺🇸Omaha, Nebraska, United States
Exelixis Clinical Site #75
🇺🇸Portland, Oregon, United States
Exelixis Clinical Site #60
🇺🇸Orlando, Florida, United States
Exelixis Clinical Site #33
🇭🇰Hong Kong, Hong Kong
Exelixis Clinical Site #25
🇭🇰Hong Kong, Hong Kong