Colorectal Cancer
Conditions
Keywords
Colorectal Cancer
Brief summary
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.
Interventions
DRUGXL092
Supplied as tablets; administered orally daily.
DRUGAtezolizumab
Supplied as 1200 milligrams (mg)/20 milliliter (mL) vials; administered as a 1200 mg intravenous (IV) infusion once in a 3-week cycle (q3w).
DRUGRegorafenib
Supplied as 40 mg tablets; administered orally daily at 160 mg for the first 21 days of each 28-day cycle.
Sponsors
Exelixis
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Key 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. Key
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. Note: Other protocol defined Inclusion/
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Overall Survival (OS) of XL092 + Atezolizumab Versus Regorafenib in All Randomized Participants | Up to 32 months |
| Overall Survival (OS) of XL092 + Atezolizumab Versus Regorafenib in Randomized Non-Liver Metastases (NLM) Participants | Up to 32 months |
Secondary
| Measure | Time frame |
|---|---|
| Objective Response Rate (ORR) as Assessed by the Investigator | Up to 36 months |
| Number of Participants with Treatment Emergent Adverse Events (TEAEs) | Up to 36 months |
| Progression-Free Survival (PFS) as Assessed by the Investigator | Up to 26 months |
| Time to Maximum Observed Plasma Drug Concentration (Tmax) of XL092 | Predose up to 72 hours postdose |
| Number of Participants who Develop Antidrug Antibodies (ADA) Against Atezolizumab | Up to 36 months |
| Maximum Observed Plasma Drug Concentration (Cmax) of XL092 | Predose up to 72 hours postdose |
| Duration of Response (DOR) as Assessed by the Investigator | Up to 36 months |
Countries
Australia, Belgium, France, Germany, Hong Kong, Hungary, New Zealand, Poland, Portugal, Singapore, South Korea, Spain, Taiwan, Thailand, United Kingdom, United States
Outcome results
None listed