Clinical trial · Interventional
Avelumab Combined With Cetuximab and Irinotecan for Treatment Refractory Metastatic Colorectal Microsatellite Stable Cancer
Avelumab Combined With Cetuximab and Irinotecan for Treatment Refractory Metastatic Colorectal Microsatellite Stable Cancer - A Proof of Concept, Open Label Non-randomized Phase IIa Study. The AVETUXIRI Trial
- Source
- ClinicalTrials.gov
- Retrieved
- Sep 8, 2026
- Layer
- normalized (units and labels harmonized; values unchanged)
- Run
- ING-CLINICALTRIALS-20260908-000001
Summary
Brief summary (as posted)
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.
Conditions
Conditions (1)
Free-text conditions as registered, with the CancerIndex entity they were reconciled to and the match type.
| Condition (as posted) | Mapped entity | Match | Confidence |
|---|---|---|---|
| Colorectal Neoplasms, Malignant | Malignant Colorectal Neoplasm | ONTOLOGY_EXACT | 0.98 |
Interventions
Interventions (3)
| Intervention | Type | Mapped drug | Match |
|---|---|---|---|
| Avelumab | Drug | Avelumab | ALIAS |
| Cetuximab Injection | Drug | Cetuximab | ALIAS |
| Irinotecan | Drug | Irinotecan | ALIAS |
Design
Arms and outcomes
Arms (1)
- type
- EXPERIMENTAL
- label
- Avelumab, Cetuximab, Irinotecan
- description
- Avelumab : administrated at a fixed dose of 10 mg/kg once every 2- week. Cetuximab: administered at 400 mg/m2 loading dose week 1, 250 mg/m2 from week 2 followed by 500 mg/m2 from week 3. Irinotecan: administrated every 2 weeks (180 mg/m2).
- interventionNames
- Drug: Avelumab
- Drug: Cetuximab Injection
- Drug: Irinotecan
Primary outcomes (1)
- measure
- Tumor response rate
- timeFrame
- Up to 19 weeks
- 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.
Secondary outcomes (1)
- measure
Eligibility
Eligibility (as posted)
- Sex
- All
- Minimum age
- 18 Years
- Maximum age
- 100 Years
Show eligibility criteria text
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. * For RAS WT, non-progressive disease following anti-EGFR treatment.
References
Publications (1)
- DERIVEDHuyghe N, Benidovskaya E, Masoodi T, Sinapi I, De Cuyper A, Vempalli F, Beyaert S, Bouzin C, Osorio FM, Ferraro L, van Baren N, Helaers R, Goffette P, Ghaye B, van Maanen A, Castella ML, Ceccarelli M, Bedognetti D, Galon J, Hendrickx WRL, Carrasco J, Van den Eynde M. Impact of the tumor immune contexture in microsatellite-stable metastatic colorectal cancer treated with avelumab, cetuximab, and irinotecan. Cell Rep Med. 2025 Jul 15;6(7):102201. doi: 10.1016/j.xcrm.2025.102201. Epub 2025 Jun 24. PMID 40562041