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

Colorectal Cancer Clinical Trial

— STELLAR-303  

Official title:

A Randomized Open-Label Phase 3 Study of XL092 + Atezolizumab vs Regorafenib in Subjects With Metastatic Colorectal Cancer

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05425940
• Other study ID #: XL092-303
• Secondary ID: 2021-003243-21
• Status: Recruiting
• Phase: Phase 3
• Start date: September 7, 2022
• Est. completion date: February 2026

Study information

• Verified date: March 2024
• Source: Exelixis
• Contact: Exelixis Clinical Trials
• Phone: 1-888-EXELIXIS (888-393-5494)
• Email: druginfo[@]exelixis.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 874
• Est. completion date: February 2026
• Est. primary completion date: August 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Colorectal Cancer
• Colorectal Neoplasms

Intervention

Drug:
• XL092
Supplied as tablets; administered orally daily
• Atezolizumab
Supplied as 1200 mg/20 mL vials; administered as a 1200 mg IV infusion once in a 3-week cycle (q3w)
• Regorafenib
Supplied as 40 mg tablets; administered orally daily at 160 mg for the first 21 days of each 28-day cycle

Locations

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

Sponsors (1)

Lead Sponsor	Collaborator
Exelixis

Countries where clinical trial is conducted

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

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Progression-Free Survival (PFS) as assessed by the Investigator per RECIST 1.1	Defined as the time randomization to the earlier of either radiographic progressive disease (PD) as assessed by the Investigator per RECIST 1.1 or death from any cause.	Approximately 26 months after the first subject is randomized.
Other	Objective Response Rate (ORR) as assessed by the Investigator per RECIST 1.1	Defined as the proportion of subjects experiencing a confirmed complete response (CR) or confirmed partial response (PR) as assessed by the Investigator per RECIST 1.1 criteria.	Up to 36 months after the first subject is randomized.
Other	Duration of Response (DOR) as assessed by the Investigator per RECIST 1.1	Defined as the time from the first documentation of objective response (subsequently confirmed at a visit = 28 days later) to either radiographic disease progression or death due to any cause.	Up to 36 months after the first subject is randomized.
Primary	Overall Survival	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.	Approximately 32 months after the first subject is randomized.
Secondary	Overall Survival	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.	Approximately 32 months after the first subject is randomized.