120P - Avelumab (AVE), cetuximab (CET) and irinotecan (IRI) for treatment refractory microsatellite stable (MSS) metastatic colorectal cancer (mCRC): Characterization of the circulating immune response in the AVETUXIRI phase II trial

Background

Clinical efficacy and safety of AVE, CET and IRI have previously been reported for the treatment of refractory MSS mCRC. Here, we aim to characterize the systemic immune response and investigate its potential role in response to immunotherapy.

Methods

MSS, chemo refractory (anti-EGFR refractory if RAS wild-type) mCRC patients were enrolled (RAS wild-type: 28 patients, RAS mutated: 27 patients) and treated with CET and IRI from week 1 (W1) and AVE from W3. Clinical objectives, including safety and efficacy were previously reported. Using high-dimensional flow cytometry and FlowJo™, peripheral blood mononuclear cells were characterized for immune populations’ phenotypes (including B, T, natural killer (NK) and myeloid cell populations) and proportions. Modifications of immune cells proportions were analysed over time (sequential blood samples were collected at W0, W3, and W11) and correlated with response, progression-free survival (PFS) and overall survival (OS) of included patients. P-values were calculated using the Wilcoxon test.

Results

Of the 55 treated patients, 148 blood samples (W0: 55, W3: 53, W11: 40) were available for flow cytometry analyses. Overall, B, T, NK, and myeloid cell populations remained stable over time and were not associated with clinical efficacy. Some T and NK cell subpopulations showed variations. Regardless of RAS mutational status, a decrease of T_H17 frequency over time was associated with PFS ≤ 6 months (p=0.0018), OS ≤ 12 months (0.0083) and tumour growth (p=1.6e-05). At baseline, a lower frequency of circulating NKT cells was associated with tumour response (p=0.02), and an increase of NKT cell frequency over time was associated with tumour response (p=0.00076), PFS > 6 months (p=0.0086) and OS > 12 months (p=0.0069).

Conclusions

Independently of RAS mutational status, modifications of T_H17 and NKT cell frequencies in MSS mCRC patients’ blood included in the AVETUXIRI trial seems to be associated with tumour response and patients’ survival after treatment.

Clinical trial identification

NCT03608046.

Legal entity responsible for the study

Cliniques Universitaires Saint Luc.

Funding

This academic study (investigator sponsored trial) received a fixed grant and supply for the study drugs (avelumab and cetuximab) from Merck.

Disclosure

All authors have declared no conflicts of interest.