Study of XL092 + Atezolizumab vs Regorafenib in Subjects With Metastatic Colorectal Cancer (STELLAR-303)

Prior treatment

• Prior treatment with XL092, regorafenib, trifluridine/tipiracil, or PD-L1/PD-1 targeting ICIs.
• 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, except for superficial skin cancers, or localized, low-grade tumors deemed cured and not treated with systemic therapy. Incidentally diagnosed prostate cancer is allowed if assessed as stage ≤ T2N0M0 and Gleason score ≤ 6.
• Administration of a live, attenuated vaccine within 30 days before randomization.
• 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 anticancer 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. Subjects with clinically relevant ongoing complications from prior radiation therapy are not eligible.
• 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.
• Major surgery (eg, GI surgery, removal or biopsy of brain metastasis) within 4 weeks prior to randomization. Complete wound healing from major or minor surgery must have occurred at least 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.

Other illness

• History of psychiatric illness likely to interfere with ability to comply with protocol requirements or give informed consent.
• Inability to swallow study treatment formulation, inability to receive IV administration, or presence of GI condition that might affect the absorption of study drug (eg, PEG tube).
• The subject has uncontrolled, significant intercurrent or recent illness including, but not limited to, the following conditions: (please refer to the protocol)

Lab values

• Corrected QT interval calculated by the Fridericia formula (QTcF) > 460 ms within 10 days before randomization per electrocardiogram (ECG) before randomization (see Section 5.7.4 for Fridericia formula).

Other

• Pregnant or lactating females.

• Subjects with histologically or cytologically confirmed adenocarcinoma of the colon or rectum
• Fertile subjects and their partners must agree to use highly effective methods of contraception (defined in Appendix H) during the course of the study and for the following durations after the last dose of treatment (whichever is later)
• Female subjects of childbearing potential must not be pregnant at screening. Female subjects are considered to be of childbearing potential unless one of the following criteria is met: permanent sterilization (hysterectomy, bilateral salpingectomy, or bilateral oophorectomy) or documented postmenopausal status (defined as 12 months of consecutive amenorrhea in a female > 45 years-of-age in the absence of other biological or physiological causes. In addition, females < 55 years-of-age must have a serum follicle-stimulating hormone [FSH] level > 40 mIU/mL to confirm menopause).
• Has received the following SOC anticancer therapies as prior therapy for metastatic CRC and has radiographically progressed, is refractory or intolerant to these therapies. Prior investigational therapies are allowed.
• Measurable disease according to Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1; Eisenhauer et al 2009) 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 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, based upon meeting all of the following laboratory criteria within 10 days before randomization.
• Capable of understanding and complying with the protocol requirements and must have signed the informed consent document.