PHASE Ib STUDY WITH THE COMBINATION OF LB–100 (PP2A INHIBITOR) AND ATEZOLIZUMAB (PD–L1 INHIBI-TOR) IN METASTATIC COLORECTAL CANCER PATIENTS – The CoLBAt Trial

Prior treatment

• Symptomatic or actively progressing central nervous system (CNS) metastases. Asymptomatic patients with treated or untreated CNS lesions are eligible, provided that all of the following criteria are met: Measurable disease, per RECIST v1.1, must be present outside the CNS; The patient has no histology of intracranial haemorrhage or spinal cord haemorrhage; The patient has not undergone stereotactic radiotherapy within 7 days prior to initiation of study treatment, whole−brain radiotherapy within 14 days prior to initiation of study treatment, or neurosurgical resection within 28 days prior to initiation of study treatment; The patient has no ongoing requirement for corticosteroids as therapy for CNS disease; If the patient is receiving anti−convulsant therapy, the dose is considered stable.
• Uncontrolled tumour−related pain. Patients requiring pain medication must be on a stable regimen at study entry. Symptomatic lesions (e.g., bone metastases or metastases causing nerve impingement) amenable to palliative radiotherapy should be treated prior to enrolment. Patients should be recovered from the effects of radiation. There is no required minimum recovery period. Asymptomatic metastatic lesions that would likely cause functional deficits or intractable pain with further growth (e.g., epidural metastasis that is not currently associated with spinal cord compression) should be considered for loco−regional therapy, if appropriate, prior to enrolment.
• Active or history of auto–immune disease or immune deficiency, including, but not limited to, myasthenia gravis, myositis, autoimmune hepatitis, systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, anti-phospholipid antibody syndrome, Wegener granulomatosis, Sjögren syndrome, Guillain−Barré syndrome, or multiple sclerosis (see Appendix 2 for a more comprehensive list of autoimmune diseases and immune deficiencies), with the following exceptions: Patients with a history of autoimmune−related hypothyroidism who are on thyroid replacement hormone are eligible for the study; Patients with controlled Type 1 diabetes mellitus who are on an insulin regimen are eligible for the study; Patients with eczema, psoriasis, lichen simplex chronicus or vitiligo with dermatologic manifestations only (e.g. patients with psoriatic arthritis are excluded) are eligible for the study provided all of the following conditions are met: Rash must cover <10% of body surface area; Disease is well controlled at baseline and requires only low−potency topical corticosteroids; There has been no occurrence of acute exacerbations of the underlying condition requiring psoralen plus ultraviolet A radiation, methotrexate, retinoids, biologic agents, oral cacineurin inhibitors, or high−potency or oral corticosteroids within the previous 12 months.
• Significant cardiovascular disease (such as New York Heart Association Class II or greater cardiac disease, myocardial infarction, or cerebrovascular accident) within 3 months prior to initiation of study treatment, unstable arrhythmia, or unstable angina.

Other illness

• History of idiopatic pulmonary fibrosis, organizing pneumonia (e.g., bronchiolitis obliterans), drug−induced pneumonitis, or idiopathic pneumonitis, or evidence of active pneumonitis on screening chest CT scan. History of radiation pneumonitis in the radiation field (fibrosis) is permitted.
• Active tuberculosis.

Lab values

• Uncontrolled symptomatic hypercalcemia (ionized calcium > 1.5 mmol/L, calcium >12 mg/dL, or corrected calcium greater than ULN).

Other

• Uncontrolled pleural effusion, pericardial effusion, or ascites requiring recurrent drainage procedures (once monthly or more frequently). Patients with indwelling catheters are allowed.

• Histological or cytological confirmed CRC
• Measurable disease per Response Evaluation Criteria in Solid Tumours version 1.1 (RECIST v1.1). Previously irradiated lesions can be considered as measurable disease only if progressive disease has been unequivocally documented at that site since radiation
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.