study of xl092 + atezolizumab vs regorafenib in subjects with metastatic colorectal cancer

Conditions: Colorectal Cancer

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.


Eligibility criteria:
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.

Keywords: colorectal cancer