635P - Avelumab (AVE) combined with cetuximab (CET) and irinotecan (IRI) for the treatment of refractory microsatellite stable (MSS) metastatic colorectal cancer (mCRC): The AVETUXIRI phase II study

Background

Cetuximab could mediate, independently from RAS mutation, an immunogenic tumor cell death and antitumor immune response. This trial explores the efficacy and safety of AVE, CET and IRI for the treatment of refractory MSS mCRC.

Methods

Chemo-refractory (+anti-EGFR refractory if RAS wt) MSS, mCRC patients (pts) were enrolled in 3 cohorts (A: RAS wt, B & C: RAS mut) and treated with CET (500 mg/m²/Q2W), IRI (150 mg/m²/Q2W) and AVE (10 mg/kg/Q2W). Primary endpoints were safety, overall response rate (ORR) (cohorts A-B) and 6 months progression-free survival rate (6m-PFSR) (cohort C). Secondary and exploratory endpoints included disease control rate (DCR), PFS, OS and immunoscore (IS) biomarker. Based on a Simon 2-stage design (α=0.1; β=0.2) for ORR (cohorts A: P0/P1=0.15/0.33 – B: P0/P1=0.09/0.25) and 6m-PFSR (cohort C: P0/P1=0.15/0.31), 10+18 (A); 13+15 (B) and 14+25 (C) pts were needed. At least 2+5 (A); 2+3 (B) and 3+6 (C) pts must reach ORR (A-B) or 6m-PFSR (C) for efficacy objectives. Immunofluorescence (CD3, CD8 densities) was performed on baseline metastasis biopsies to generate IS.

Results

57 pts (median 62 yrs, 73.7% male, 84.2% left-sided, 86.0% synchr. mCRC) were included and 55 pts treated. Any treatment-emergent adverse event (AE) grade >=3 occurred in 35 pts (63.6%; diarrhea in 11 pts, 20.0%). Immune-related AEs grade >=3 appeared in 2 pts (3.6%; 1 acute kidney injury, 1 cholangitis). Efficacy results are summarized.

Table: 635P

Independently of RAS mutation, high IS was associated with greater tumor shrinkage (OR=8.3, p<0.01), DCR (OR=8.0, p=0.05), PFS (median 7.1 vs 3.1 months; HR=0.29, p<0.01) and OS (median 12.9 vs 7.2 months; HR=0.62, p=0.19).

Conclusions

Despite good tolerability, AVETUXIRI trial did not reach its efficacy endpoint. IS could be a predictive biomarker for selecting patients with potential treatment benefits.

Clinical trial identification

NCT03608046.

Editorial acknowledgement

Legal entity responsible for the study

Institut Roi Albert II - Cliniques universitaires St-Luc.

Funding

Merck Serono.

Disclosure

All authors have declared no conflicts of interest.