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

Study Overview
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Brief Summary
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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 after or are intolerant to standard-of-care (SOC) therapy.

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

Conditions
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Colorectal Cancer

Intervention / Treatment
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* Drug: XL092
* Drug: Atezolizumab
* Drug: Regorafenib


Participation Criteria
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Eligibility Criteria
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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. Radiographic progression during treatment with or within 3 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. 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. Concomitant anticoagulation with oral anticoagulants and platelet inhibitors. Corrected QT interval calculated by the Fridericia formula (QTcF) > 460 ms within 10 days before randomization. Pregnant or lactating females. Administration of a live, attenuated vaccine within 30 days before randomization.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Experimental Arm<br>Subjects with mCRC will receive XL092 + atezolizumab | Drug: XL092<br>* Supplied as tablets; administered orally daily<br>Drug: Atezolizumab<br>* Supplied as 1200 mg/20 mL vials; administered as a 1200 mg IV infusion once in a 3-week cycle (q3w)<br>* Other names: Tecentriq®;|
| Active Comparator: Control Arm<br>Subjects with mCRC will receive active comparator of regorafenib | Drug: Regorafenib<br>* Supplied as 40 mg tablets; administered orally daily at 160 mg for the first 21 days of each 28-day cycle<br>* Other names: Stivarga®;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Efficacy in RAS wild-type (WT) subjects | The primary objective of this study is to evaluate the efficacy of XL092 + atezolizumab versus regorafenib in subjects with RAS wild-type MSS/MSI-low mCRC who have progressed after or are intolerant to SOC therapy. | Approximately 26 months after the first subject is randomized | 
| Duration of Overall Survival (OS) | Defined as the time from randomization to death due to any cause | Approximately 26 months after the first subject is randomized | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Colorectal Cancer