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.
Brief Title
Study of XL092 + Atezolizumab vs Regorafenib in Participants With Metastatic Colorectal Cancer
Categories
Completion Date
Completion Date Type
Estimated
Conditions
Colorectal Cancer
Eligibility 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/Exclusion criteria may apply.
* 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/Exclusion criteria may apply.
Inclusion Criteria
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.
Inclusion/
* 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.
Inclusion/
Gender
All
Gender Based
false
Keywords
Colorectal Cancer
Healthy Volunteers
No
Last Update Post Date
Last Update Post Date Type
Estimated
Last Update Submit Date
Minimum Age
18 Years
NCT Id
NCT05425940
Org Class
Industry
Org Full Name
Exelixis
Org Study Id
XL092-303
Overall Status
Active, not recruiting
Phases
Phase 3
Primary Completion Date
Primary Completion Date Type
Estimated
Official Title
A Randomized Open-Label Phase 3 Study of XL092 + Atezolizumab vs Regorafenib in Subjects With Metastatic Colorectal Cancer
Primary Outcomes
Outcome Measure
Overall Survival (OS) of XL092 + Atezolizumab Versus Regorafenib in All Randomized Participants
Outcome Time Frame
Up to 32 months
Outcome Measure
Overall Survival (OS) of XL092 + Atezolizumab Versus Regorafenib in Randomized Non-Liver Metastases (NLM) Participants
Outcome Time Frame
Up to 32 months
Secondary Ids
Secondary Id
2021-003243-21
Secondary Outcomes
Outcome Time Frame
Up to 26 months
Outcome Measure
Progression-Free Survival (PFS) as Assessed by the Investigator
Outcome Time Frame
Up to 36 months
Outcome Measure
Duration of Response (DOR) as Assessed by the Investigator
Outcome Time Frame
Up to 36 months
Outcome Measure
Objective Response Rate (ORR) as Assessed by the Investigator
Outcome Time Frame
Up to 36 months
Outcome Measure
Number of Participants with Treatment Emergent Adverse Events (TEAEs)
Outcome Time Frame
Predose up to 72 hours postdose
Outcome Measure
Maximum Observed Plasma Drug Concentration (Cmax) of XL092
Outcome Time Frame
Predose up to 72 hours postdose
Outcome Measure
Time to Maximum Observed Plasma Drug Concentration (Tmax) of XL092
Outcome Time Frame
Up to 36 months
Outcome Measure
Number of Participants who Develop Antidrug Antibodies (ADA) Against Atezolizumab
Start Date
Start Date Type
Actual
Status Verified Date
First Post Date
First Post Date Type
Actual
First Submit Date
First Submit QC Date
Std Ages
Adult
Older Adult
Maximum Age Number (converted to Years and rounded down)
999
Minimum Age Number (converted to Years and rounded down)
18
Investigators
Investigator Type
Principal Investigator
Investigator Name
Chaoyuan Kuang
Investigator Email
chaoyuan.kuang@einsteinmed.edu
Investigator Phone
617-398-1715
Investigator Department
Medicine
Investigator Division
Oncology
Investigator Sponsor Organization
External
Study Department
Oncology (Medical/Hematologic)
Study Division
Medical and Hematologic Oncology
Categories Mesh Debug
Gastrointestinal (GI) Cancers --- COLORECTAL NEOPLASMS
Gastrointestinal (GI) Cancers --- INTESTINAL NEOPLASMS
Gastrointestinal (GI) Cancers --- GASTROINTESTINAL NEOPLASMS
Gastrointestinal (GI) Cancers --- DIGESTIVE SYSTEM NEOPLASMS
Cancer --- NEOPLASMS BY SITE
Cancer --- NEOPLASMS
Gastrointestinal (GI) Cancers --- DIGESTIVE SYSTEM DISEASES
Digestive System --- DIGESTIVE SYSTEM DISEASES
Liver --- DIGESTIVE SYSTEM DISEASES
Gastrointestinal (GI) Cancers --- GASTROINTESTINAL DISEASES
Digestive System --- GASTROINTESTINAL DISEASES
Gastrointestinal (GI) Cancers --- COLONIC DISEASES
Digestive System --- COLONIC DISEASES
Gastrointestinal (GI) Cancers --- INTESTINAL DISEASES
Digestive System --- INTESTINAL DISEASES
MeSH Terms
COLORECTAL NEOPLASMS
INTESTINAL NEOPLASMS
GASTROINTESTINAL NEOPLASMS
DIGESTIVE SYSTEM NEOPLASMS
NEOPLASMS BY SITE
NEOPLASMS
DIGESTIVE SYSTEM DISEASES
GASTROINTESTINAL DISEASES
COLONIC DISEASES
INTESTINAL DISEASES
RECTAL DISEASES
ATEZOLIZUMAB
REGORAFENIB