The aim of this study is to evaluate the efficacy of the addition of Atezolizumab to FOLFOXIRI plus bevacizumab as first line treatment of patients with pMMR and Immunoscore IC-high metastatic colorectal cancer in terms of Progression Free Survival (PFS).
Histologically proven diagnosis of colorectal cancer;
Initially unresectable metastatic colorectal cancer not previously treated with chemotherapy for metastatic disease;
Proficient mismatch repair (pMMR) status in tumour tissue (primary or metastatic), as determined by a local laboratory assay in a CLIA- or similarly certified;
Immunoscore IC-high status in tumour tissue (primary or metastatic), as determined by a sponsor-defined central laboratory (HEGP, AP-HP, INSERM, France).
Radiotherapy to any site within 4 weeks before the study;
Previous adjuvant oxaliplatin-containing chemotherapy;
Previous treatment with bevacizumab;
Prior treatment with CD137 agonists, anti-CTLA4, anti-PD-1, or anti-PD-L1 therapeutic antibody or pathway-targeting agents;
Parallel
Atezolizumab
Drug840 mg iv over 30 minutes (60 minutes at first infusion) day 1
Bevacizumab
Drug5 mg/kg iv over 90 minutes at cycle 1 (if well tolerated, it is administered over 60 minutes at cycle 2, and over 30 minutes at cycle 3) day 1
Irinotecan (CPT-11)
Drug165 mg/sqm iv over 60 minutes day 1
Oxaliplatin
Drug85 mg/sqm iv over 2 hours day 1
Leucovorin
Drug200 mg/sqm iv over 2 hours day 1
Fluorouracil (5-FU)
Drug3200 mg/sqm 48 h-continuous infusion, starting on day 1
Progression Free Survival (PFS)
PFS is defined as the time from randomization to the first documentation of objective disease progression or death due to any cause, whichever occurs first. PFS will be censored on the date of the last evaluable on study tumor assessment documenting absence of progressive disease for patients who are alive, on study and progression free at the time of the analysis. Alive patients having no tumor assessments after baseline will have time to event censored on the date of randomization.
Overall Toxicity Rate
Overall Toxicity Rate is defined as the percentage of patients, relative to the total of enrolled subjects, experiencing any adverse event, according to National Cancer Institute Common Toxicity Criteria (version 5.0), during the induction and the maintenance phases of treatment.
Toxicity Rate
Toxicity Rate is defined as the percentage of patients, relative to the total of enrolled subjects, experiencing a specific adverse event of grade 3/4, according to National Cancer Institute Common Toxicity Criteria (version 5.0), during the induction and the maintenance phases of treatment.
Objective Response Rate
Objective Response Rate (ORR) is defined as the percentage of patients, relative to the total of enrolled subjects, achieving a complete (CR) or partial (PR) response, according to RECIST 1.1 criteria, during the induction and the maintenance phases of treatment. The determination of clinical response will be based on investigator reported measurements. Responses will be evaluated every 8 weeks.
Immuno-related Objective Response Rate
Immuno-related Objective Response Rate (irORR) is defined as the percentage of patients, relative to the total of enrolled subjects, achieving a complete (CR) or partial (PR) response, according to immune-modified RECIST criteria, during the induction and the maintenance phases of treatment. The determination of clinical response will be based on investigator reported measurements. Responses will be evaluated every 8 weeks.
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Gruppo Oncologico del Nord-Ovest
Lead sponsor
Hoffmann-La Roche
Collaborator
