Cancer immunotherapy with immunostimulatory antibodies targeting the CTLA-4 or PD-1/PD-L1 pathways has demonstrated its efficacy in variable proportions of cancer. For metastatic colorectal cancer (mCRC) it appeared that only the small subgroup of patients with MSI-H tumors (microsatellite instability-high phenotype) had a clinically meaningful response to the anti-PD-1- L1 antibodies. In the majority group of non-MSI-H CRC (90-95% of patients), current research expect that additional means would be able to render the tumor "immunogenic" (like MSI-H CRC) and increase the intratumoral immune infiltrate which is the prerequisite to observe a benefit from PD1-PD-L1 inhibitors. Combinations of immune checkpoint inhibitors and procedures that increase intratumoral immune responses, such as targeted therapy, are actively explored.
Name: Cetuximab Injection
Description: The overall tumor response rate (ORR) defined as the proportion of all included patient with a confirmed best overall tumor response of PR or CR according to irRECIST 1.1 occuring until 19 weeks after study treatment start.Measure: Tumor response rate Time: Up to 19 weeks
Description: Safety will be controlledMeasure: Adverse events Time: Up to 19 weeks
Single Group Assignment
There is one SNP
Inclusion Criteria: - Age 18 and over, Performance status: ECOG 0-1 - Histologically proven metastatic colorectal adenocarcinoma, refractory to standard chemotherapy (fluoropyrimidine, oxaliplatin, irinotecan) and anti-EGFR treatment (only for RAS WT tumor) - Measurable disease (RECIST 1.1) - Metastasis accessible for sequential biopsies - Patient consent for metastasis biopsies in the study protocol - BRAF V600E wild-type and MSS tumors - Adequate normal organ and marrow function (see adequate section of the full protocol for definition) - Life expectancy of at least 4 months Exclusion Criteria: - Concurrent chronic systemic immune therapy, chemotherapy, or hormone therapy that are not indicated in the study protocol - Systemic autoimmune disease, - Chronic treatment with corticoids or other immunosuppressive treatment - Clinically significant cardiac, lung or general disease despite optimal treatment - Non-progressive disease following irinotecan-based treatment. --- V600E ---