Clinical trial NCT05425940: Study of XL092 + Atezolizumab vs Regorafenib in Subjects With Metastatic Colorectal Cancer
Official title: A Randomized Open-Label Phase 3 Study of XL092 + Atezolizumab vs Regorafenib in Subjects With Metastatic Colorectal Cancer
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE3
Conditions: Colorectal Cancer
Keywords: Colorectal Cancer
Lead sponsor: Exelixis
Sponsor class: INDUSTRY
First posted: 2022-06-21
Enrollment: 874
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: Inclusion Criteria:

* 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.

Exclusion Criteria:

* 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.

Primary outcomes:
measure: Overall Survival
timeFrame: Approximately 32 months after the first subject is randomized.
Secondary outcomes:
measure: Overall Survival
timeFrame: Approximately 32 months after the first subject is randomized.
Other outcomes:
measure: Progression-Free Survival (PFS) as assessed by the Investigator per RECIST 1.1
timeFrame: Approximately 26 months after the first subject is randomized.
measure: Objective Response Rate (ORR) as assessed by the Investigator per RECIST 1.1
timeFrame: Up to 36 months after the first subject is randomized.
measure: Duration of Response (DOR) as assessed by the Investigator per RECIST 1.1
timeFrame: Up to 36 months after the first subject is randomized.
Locations:
city: Jonesboro
country: United States
facility: Exelixis Clinical Site #65
state: Alabama
city: Phoenix
country: United States
facility: Exelixis Clinical Site #30
state: Arizona
city: Tucson
country: United States
facility: Exelixis Clinical Site #70
state: Arizona
city: Duarte
country: United States
facility: Exelixis Clinical Site #9
state: California
city: La Jolla
country: United States
facility: Exelixis Clinical Site #55
state: California
city: Los Angeles
country: United States
facility: Exelixis Clinical Site #77
state: California
city: Orange
country: United States
facility: Exelixis Clinical Site #105
state: California
city: Santa Monica
country: United States
facility: Exelixis Clinical Site #80
state: California
city: Santa Rosa
country: United States
facility: Exelixis Clinical Site #5
state: California
city: Sylmar
country: United States
facility: Exelixis Clinical Site #82
state: California
city: Torrance
country: United States
facility: Exelixis Clinical Site #58
state: California
city: Whittier
country: United States
facility: Exelixis Clinical Site #81
state: California
city: New Haven
country: United States
facility: Exelixis Clinical Site #125
state: Connecticut
city: Miami Beach
country: United States
facility: Exelixis Clinical Site #16
state: Florida
city: Orlando
country: United States
facility: Exelixis Clinical Site #60
state: Florida
city: Marietta
country: United States
facility: Exelixis Clinical Site #4
state: Georgia
city: Joliet
country: United States
facility: Exelixis Clinical Site #3
state: Illinois
city: Indianapolis
country: United States
facility: Exelixis Clinical Site #102
state: Indiana
city: Westwood
country: United States
facility: Exelixis Clinical Site #10
state: Kansas
city: Lexington
country: United States
facility: Exelixis Clinical Site #47
state: Kentucky
city: New Orleans
country: United States
facility: Exelixis Clinical Site #7
state: Louisiana
city: Saint Louis
country: United States
facility: Exelixis Clinical Site #22
state: Missouri
city: Billings
country: United States
facility: Exelixis Clinical Site #8
state: Montana
city: Omaha
country: United States
facility: Exelixis Clinical Site #1
state: Nebraska
city: Albuquerque
country: United States
facility: Exelixis Clinical Site #15
state: New Mexico
city: Bronx
country: United States
facility: Exelixis Clinical Site #17
state: New York
city: New York
country: United States
facility: Exelixis Clinical Site #11
state: New York
city: New York
country: United States
facility: Exelixis Clinical Site #59
state: New York
city: Charlotte
country: United States
facility: Exelixis Clinical Site #74
state: North Carolina
city: Cincinnati
country: United States
facility: Exelixis Clinical Site #6
state: Ohio
city: Oklahoma City
country: United States
facility: Exelixis Clinical Site #12
state: Oklahoma
city: Portland
country: United States
facility: Exelixis Clinical Site #75
state: Oregon
city: Philadelphia
country: United States
facility: Exelixis Clinical Site #106
state: Pennsylvania
city: Pittsburgh
country: United States
facility: Exelixis Clinical Site #18
state: Pennsylvania
city: Pittsburgh
country: United States
facility: Exelixis Clinical Site #103
state: Pennsylvania
city: Greenville
country: United States
facility: Exelixis Clinical Site #24
state: South Carolina
city: Chattanooga
country: United States
facility: Exelixis Clinical Site #56
state: Tennessee
city: Nashville
country: United States
facility: Exelixis Clinical Site #76
state: Tennessee
city: Nashville
country: United States
facility: Exelixis Clinical Site #133
state: Tennessee
city: Fairfax
country: United States
facility: Exelixis Clinical Site #450
state: Virginia
city: Roanoke
country: United States
facility: Exelixis Clinical Site #14
state: Virginia
city: Seattle
country: United States
facility: Exelixis Clinical Site #13
state: Washington
city: Seattle
country: United States
facility: Exelixis Clinical Site #32
state: Washington
city: Seattle
country: United States
facility: Exelixis Clinical Site #89
state: Washington
city: Spokane
country: United States
facility: Exelixis Clinical Site #2
state: Washington
city: Albury
country: Australia
facility: Exelixis Clinical Site #83
city: Bankstown
country: Australia
facility: Exelixis Clinical Site #53
city: Bedford Park
country: Australia
facility: Exelixis Clinical Site #117
city: Heidelberg
country: Australia
facility: Exelixis Clinical Site #97
city: Melbourne
country: Australia
facility: Exelixis Clinical Site #19
city: Melbourne
country: Australia
facility: Exelixis Clinical Site #23
city: Port Macquarie
country: Australia
facility: Exelixis Clinical Site #27
city: Woodville South
country: Australia
facility: Exelixis Clinical Site #64
city: Antwerp
country: Belgium
facility: Exelixis Clinical Site #43
city: Brussels
country: Belgium
facility: Exelixis Clinical Site #51
city: Namur
country: Belgium
facility: Exelixis Clinical Site #35
city: Besançon
country: France
facility: Exelixis Clinical Site #52
city: Dijon
country: France
facility: Exelixis Clinical Site #84
city: Herbault
country: France
facility: Exelixis Clinical Site #88
city: Lyon
country: France
facility: Exelixis Clinical Site #71
city: Marseille
country: France
facility: Exelixis Clinical Site #87
city: Paris
country: France
facility: Exelixis Clinical Site #38
city: Suresnes
country: France
facility: Exelixis Clinical Site #93
city: Hannover
country: Germany
facility: Exelixis Clinical Site #127
state: Niedersach
city: Dresden
country: Germany
facility: Exelixis Clinical Site #109
city: Frankfurt am Main
country: Germany
facility: Exelixis Clinical Site #113
city: Hamburg
country: Germany
facility: Exelixis Clinical Site #61
city: Hamburg
country: Germany
facility: Exelixis Clinical Site #63
city: München
country: Germany
facility: Exelixis Clinical Site #91
city: Hong Kong
country: Hong Kong
facility: Exelixis Clinical Site #25
city: Hong Kong
country: Hong Kong
facility: Exelixis Clinical Site #33
city: Nyíregyháza
country: Hungary
facility: Exelixis Clinical Site #128
state: Szabolcs-Szatmar-Bereg County
city: Budapest
country: Hungary
facility: Exelixis Clinical Site #41
city: Budapest
country: Hungary
facility: Exelixis Clinical Site #129
city: Debrecen
country: Hungary
facility: Exelixis Clinical Site #48
city: Győr
country: Hungary
facility: Exelixis Clinical Site #122
city: Goyang-si
country: Korea, Republic of
facility: Exelixis Clinical Site #36
city: Gyeonggi-do
country: Korea, Republic of
facility: Exelixis Clinical Site #29
city: Hwasun
country: Korea, Republic of
facility: Exelixis Clinical Site #28
city: Seongnam-si
country: Korea, Republic of
facility: Exelixis Clinical Site #37
city: Seoul
country: Korea, Republic of
facility: Exelixis Clinical Site #34
city: Seoul
country: Korea, Republic of
facility: Exelixis Clinical Site #45
city: Seoul
country: Korea, Republic of
facility: Exelixis Clinical Site #66
city: Seoul
country: Korea, Republic of
facility: Exelixis Clinical Site #46
city: Seoul
country: Korea, Republic of
facility: Exelixis Clinical Site #54
city: Seoul
country: Korea, Republic of
facility: Exelixis Clinical Site #44
city: Seoul
country: Korea, Republic of
facility: Exelixis Clinical Site #40
city: Auckland
country: New Zealand
facility: Exelixis Clinical Site #57
city: Dunedin
country: New Zealand
facility: Exelixis Clinical Site #49
city: Hamilton
country: New Zealand
facility: Exelixis Clinical Site #69
city: Wellington
country: New Zealand
facility: Exelixis Clinical Site #104
city: Bydgoszcz
country: Poland
facility: Exelixis Clinical Site #20
city: Opole
country: Poland
facility: Exelixis Clinical Site #68
city: Siedlce
country: Poland
facility: Exelixis Clinical Site #26
city: Tomaszów Mazowiecki
country: Poland
facility: Exelixis Clinical Site #42
city: Warszawa
country: Poland
facility: Exelixis Clinical Site #31
city: Almada
country: Portugal
facility: Exelixis Clinical Site #108
city: Coimbra
country: Portugal
facility: Exelixis Clinical Site #120
city: Guimarães
country: Portugal
facility: Exelixis Clinical Site #99
city: Lisboa
country: Portugal
facility: Exelixis Clinical Site #131
city: Lisboa
country: Portugal
facility: Exelixis Clinical Site #124
city: Lisboa
country: Portugal
facility: Exelixis Clinical Site #96
city: Singapore
country: Singapore
facility: Exelixis Clinical Site #132
city: Singapore
country: Singapore
facility: Exelixis Clinical Site #100
city: Singapore
country: Singapore
facility: Exelixis Clinical Site #39
city: Singapore
country: Singapore
facility: Exelixis Clinical Site #98
city: Singapore
country: Singapore
facility: Exelixis Clinical Site #94
city: Barcelona
country: Spain
facility: Exelixis Clinical Site #78
city: Barcelona
country: Spain
facility: Exelixis Clinical Site #21
city: Barcelona
country: Spain
facility: Exelixis Clinical Site #86
city: Barcelona
country: Spain
facility: Exelixis Clinical Site #112
city: Lleida
country: Spain
facility: Exelixis Clinical Site #95
city: Madrid
country: Spain
facility: Exelixis Clinical Site #116
city: Madrid
country: Spain
facility: Exelixis Clinical Site #72
city: Madrid
country: Spain
facility: Exelixis Clinical Site #67
city: Madrid
country: Spain
facility: Exelixis Clinical Site #79
city: Valencia
country: Spain
facility: Exelixis Clinical Site #90
city: Zaragoza
country: Spain
facility: Exelixis Clinical Site #121
city: Guishan
country: Taiwan
facility: Exelixis Clinical Site #119
city: Kaohsiung
country: Taiwan
facility: Exelixis Clinical Site #85
city: Kaohsiung
country: Taiwan
facility: Exelixis Clinical Site #107
city: Liuying
country: Taiwan
facility: Exelixis Clinical Site #118
city: Taichung
country: Taiwan
facility: Exelixis Clinical Site #73
city: Tainan
country: Taiwan
facility: Exelixis Clinical Site #101
city: Chiang Mai
country: Thailand
facility: Exelixis Clinical Site #62
city: Hat Yai
country: Thailand
facility: Exelixis Clinical Site #92
city: Bristol
country: United Kingdom
facility: Exelixis Clinical Site #130
state: England
city: Birmingham
country: United Kingdom
facility: Exelixis Clinical Site #110
city: Edinburgh
country: United Kingdom
facility: Exelixis Clinical Site #111
city: London
country: United Kingdom
facility: Exelixis Clinical Site #123
city: London
country: United Kingdom
facility: Exelixis Clinical Site #114
city: Romford
country: United Kingdom
facility: Exelixis Clinical Site #115
city: Sutton
country: United Kingdom
facility: Exelixis Clinical Site #126
Study officials:
References: