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Avelumab and cetuximab in combination with FOLFOX in patients with previously untreated metastatic colorectal cancer (MCRC): Results of the safety run-in phase of the phase II AVETUX trial (AIO-KRK-0216).
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2018
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ImmunodeficienciesImmunologyImmunoeditingPathologyImmunotherapeuticsImmunotherapyOncologyGastrointestinal OncologyTumor ImmunityRadiation OncologyCancer ResearchMolecular OncologySafety Run-in PhaseAutoimmune DiseaseColorectal CancerMetastatic Colorectal CancerImmune SurveillanceCancer TreatmentInterim Safety AnalysisCancer ImmunosurveillanceImmune Checkpoint InhibitorTrial ContinuationSafety AnalysisMedicine
3561 Background: Single agent PD-1/L1 inhibition is efficacious in mismatch repair deficient tumours - about 5% of MCRC patients (pts). For the remaining MCRC pts the role of immunotherapy still needs to be determined. FOLFOX and cetuximab in combination with avelumab (AVETUX regimen) in 1st line RAS/BRAF wildtype MCRC is currently evaluated in a phase II trial independent of mismatch repair status (NCT03174405). Methods: This is a single arm exploratory investigator-initiated trial planned to include 43 pts to receive mFOLFOX6 and cetuximab in combination with avelumab (AVE) (10mg/kg day 1 from cycle 2 onwards). Primary endpoint is 12 months progression-free survival rate. Secondary endpoints are response rate, tolerability and translational research evaluating tissue and serial ctDNA. A safety analysis was planned after the 15th patient has passed 2 months to inform about tolerability. Results: As of 1st of February 2018 24 of 43 pts were enrolled and treated with the AVETUX regimen at 8 German sites. The safety analysis of the run-in phase was conducted on the 1st of February after a median of 3.2 months of treatment. The following adverse events were noted: 19/5 grade 3/4 (CTC AE 4.03) in 9 patients, including neutropenia (n = 11/4), nausea (n = 3), and infection (n = 3/1), mostly related to chemotherapy with only two grade 3 AE related to AVE. In 7 out of 15 patients 9 SAEs (one related to AVE), were noted including one case of grade 3 hepatitis, which resolved quickly with steroid treatment, 4 infections/fever, one diarrhea and three nausea (in one patient). Despite the relatively high absolute rate of G3/4 toxicity and SAEs, adverse events were manageable and did not relevantly impact on treatment feasibility. Two pts developed uncomplicated fever the day after the first infusion of AVE, both among the highest T cell infiltrated tumors. The IDMC recommended trial continuation based on these safety data. Updated safety and translational data and efficacy results will be presented at the meeting. Conclusions: The interim safety analysis has supported the feasibility of the AVETUX regimen in 1st line MCRC. The trial is ongoing. Clinical trial information: NCT03174405.