Results of a phase II study evaluating monalizumab in combination with cetuximab in previously treated recurrent or metastatic squamous cell carcinoma of the head and neck (R/M SCCHN)

Background: Monalizumab (Mona) is an immune checkpoint inhibitor targeting NKG2A receptors expressed on tumor-infiltrating CD8 T and Natural Killer (NK cells). The NKG2A ligand, HLA-E, is upregulated in cancer, particularly SCCHN. Blocking NKG2A-HLA-E binding was shown to promote NK and T cell anti-tumor response. NK cell stimulation with a checkpoint inhibitor was also shown to enhance antibody dependent cellular cytotoxicity (ADCC) induced by cetuximab (Cetux). Currently, only Cetux and anti-PD1 antibodies are approved for SCCHN patients (pts) progressing after platinum-based therapy, with response rates ranging from 10-17%. Methods: This is a multicenter phase I/II trial. The phase I part was previously reported showing good safety profile of Mona/Cetux combination. In the phase II part presented here, pts received Mona (10 mg/kg q2weeks) and Cetux (loading 400 then 250 mg/m2 q1week). Patients were required to be progressing after platinum-based therapy and to have received < or = 2 prior lines of therapy. The primary endpoint was ORR per RECIST assessed every 8 weeks. Pts were treated until disease progression or unacceptable toxicity. Considering a P0 of 10%, P1 of 25%, α of 5% and power of 76%, the trial would be declared positive if > or = 8 out of the 40 enrolled patients showed a confirmed RECIST response. Results: All 40 planned pts have now been enrolled and as of March 9, 2018, 31 pts were evaluable for safety of which 26 were also evaluable for efficacy. These 31 pts received prior platinum, 45% prior anti-PD1 and 10% prior Cetux. The combination was well tolerated and 93% of adverse events (AE) were of Grade 1-2 severity with only 6 % treatment-related grade 3-4 AE. The most common AEs related to Mona were fatigue (17%), pyrexia (13%) and headache (10%). Eight out of 26 patients (31%) achieved a confirmed response (1 complete and 7 partial); 54% had SD. Remaining patients are not yet evaluable as they were enrolled recently. Updated ORR, duration of response, PFS and OS on all patients will be presented during the meeting. Conclusions: These data, if confirmed in subsequent trials, suggest that Mona/Cetux could emerge as a new treatment option for pts with heavily pretreated R/M SCCHN. Clinical trial identification: NCT02643550. Legal entity responsible for the study: Innate Pharma. Funding: Innate Pharma. Disclosure: J. Fayette: Membership on advisory board: BMS, Merck Serono, Innate Pharma. M.R. Posner: Data safety monitoring board: Merck, Cel Sci. C. Even, T. Seiwert: Advisory Board: Innate Pharma. D. Colevas: Consultant: Cota, Inc, KeyQuest Health; Research support: Bristol-Myers Squibb, IRX Therapeutics, Threshold Pharmaceuticals, AstraZeneca, Innate Pharma, PRA Health Sciences. F. Calmels, R. Zerbib, A. Boyer Chammard: Stock ownership and employment: Innate Pharma. R. Cohen: Grant to University of Pennsylvania: Innate Pharma. All other authors have declared no conflicts of interest.