3-(4-METHYLPIPERAZINE-1-CARBONYL)-7-OXABICLO[2.2.1]HEPTANE-2-CARBOXYLIC ACID for Microsatellite stable colorectal cancer

Inclusion criteria

• {"criterion_text":"- Histological or cytological confirmed CRC"}
• {"criterion_text":"- 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"}
• {"criterion_text":"- Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1."}

Exclusion criteria

• {"criterion_text":"- 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."}
• {"criterion_text":"- 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."}
• {"criterion_text":"- Uncontrolled pleural effusion, pericardial effusion, or ascites requiring recurrent drainage procedures (once monthly or more frequently). Patients with indwelling catheters are allowed."}
• {"criterion_text":"- Uncontrolled symptomatic hypercalcemia (ionized calcium > 1.5 mmol/L, calcium >12 mg/dL, or corrected calcium greater than ULN)."}
• {"criterion_text":"- 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."}
• {"criterion_text":"- 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."}
• {"criterion_text":"- Active tuberculosis."}
• {"criterion_text":"- 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."}

Primary endpoints

• {"endpoint_text":"- The main study endpoint is to determine the RP2D of LB−100 when administered in combination with standard doses of Atezolizumab, by assessing the maximum tolerated dose and incidences of adverse events.","definition_or_measurement_approach":"Determine RP2D by assessing maximum tolerated dose (MTD) and incidence of adverse events; incidence of dose-limiting toxicities (DLTs) will be used to assess tolerability."}

Secondary endpoints

• {"endpoint_text":"- The efficacy will be evaluated using the disease control rate, objective response rate, progression free survival, overall survival and duration of response.","definition_or_measurement_approach":"Efficacy measured by disease control rate (DCR), objective response rate (ORR), progression-free survival (PFS), overall survival (OS) and duration of response (DoR) per RECIST v1.1 as appropriate."}
• {"endpoint_text":"- A pharmacokinetic profile of Atezolizumab, LB−100 and the active metabolite endothall will be included by measuring plasma concentrations and determining the pharmacokinetic parameters (e.g. maximal plasma concentration, area under the curve, half–life).","definition_or_measurement_approach":"PK measured by plasma/serum concentration timepoints specified in protocol section 8.4.7; parameters include Cmax, AUC, half-life and other PK parameters."}
• {"endpoint_text":"- Additionally, relevant pharmacodynamics biomarkers will be explored.","definition_or_measurement_approach":"Exploratory PD biomarker analyses including immune profiling, serine/threonine hyperphosphorylation of white blood cells, mismatch repair deficiency status and other relevant pharmacodynamic markers correlated with clinical outcomes."}

Netherlands

Earliest CTIS Part Ii Submission Date

08-04-2024

Latest Decision Or Authorization Date

17-11-2025

Processing Time Days

588

Number Of Sites

1

Number Of Participants

37

Primary sponsor

Full Name

Het Nederlands Kanker Instituut-Antoni van Leeuwenhoek Ziekenhuis Stichting

Organisation Type

Hospital/Clinic/Other health care facility

Country Of Registered Address

Netherlands

Third parties

• {"country":"","full_name":"Hoffmann-La Roche Ltd","duties_or_roles":"Source of monetary support","organisation_type":""}