Study of XL092 + Atezolizumab vs Regorafenib in Subjects With Metastatic Colorectal Cancer
Study of XL092 + Atezolizumab vs Regorafenib in Subjects With Metastatic Colorectal Cancer
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.
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.
Colon,
Rectal
Phase III
Adults
Mol. targeted/Immunotherapy/Biologics
Atezolizumab,
Regorafenib,
XL092
Eng, Cathy
International
Vanderbilt University
03-22-2024
Eligibility
18 Years
BOTH
NO
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.
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.
