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Table 1. Recent immunotherapy approaches in head and neck squamous cell carcinoma
Stage of clinical
Immunotherapy Mecanism of action Setting
develoment
M7824 Bispecific anti-PD-L1 and anti-TGF-β Phase I Recurrent/metastatic HNSCC in second
antibody therapeutic line
Monalizumab with cetuximab New checkpoint inhibitor targeting Phase II Recurrent/metastatic HNSCC
NKG2A + anti EGFR
Danvatirsen with durvalumab Inhibitory antisense oligonucleotide Phase Ib/II Metastatic HNSCC naive of anti-PD-L1
of STAT3 + anti-PD-L1
SD101 with pembrolizumab TLR9 agonist + anti-PD-1 Phase I/II Recurrent/metastatic HNSCC, anti-PD1
naive
Epacadostat Oral IDO1 inhibitor Phase III failures Recurrent/metastatic HNSCC
Lenvatinib Broad-spectrum TKI Phase Ib/II Metastatic HNSCC, after at least one
line of chemotherapy
MEDI6974 with durvalumab Ox40 agonist antibody + anti-PD-L1 Phase Ib Before surgery with stage III-IVA HNSCC
Dendritic cell vaccination with Mature CD loaded with WT1 Phase I/II Recurrent/metastatic HNSCC
conventional chemotherapy peptides + OK-432 (TLR-4 ligand)
HNSCC: head and neck squamous cell carcinoma; EGFR: epidermal growth factor receptor; TGF: transforming growth factor

In adjuvant, trials are in progress with comparative immunotherapies or added to cisplatin or cetuximab
during radiotherapy, but there is currently no efficacy data. There is no sign of toxicity so we expect a
better tolerance than current treatments. A randomized Phase II trial compared potentiated radiotherapy
with cetuximab or pembrolizumab in inoperable patients not eligible for cisplatin. Tolerance was better in
the pembrolizumab group with a 3-4 grade toxicity of 69% vs. 88% with cetuximab. There was particularly
[7]
less mucositis and radiodermatitis with pembrolizumab .
In neoadjuvant, a phase I is in progress that combines durvalumab with TPF (cisplatin docetaxel 5FU) to
potentiate induction chemotherapy.

A phase 2 study also studied still in neoadjuvant 23 patients with high-risk HNSCC cancer (probable R1
resection or capsular rupture) who received pembrolizumab 1 to 3 weeks before surgery. There was 47%
response with an anti-tumor effect on more than 10% of the surface, including 32% major response on more
[8]
[9]
than 70% of the surface and 1 complete response . Similar results have been observed with nivolumab .
It is also possible that immunotherapy may make subsequent chemotherapy more effective, which would
favor earlier administration of immunotherapy.

NEWS IMMUNOTHERAPY
Many immunotherapy molecules with different mechanisms of action are currently under development.
[10]
A review of the 2016 literature presented the latest insights into the field of immunotherapy for HNSCC .
Many immunotherapy associations were already being tested. The goal here is to present some of these
innovations with a promising future to show the diversity of this one. Table 1 summarizes the molecules
presented.

A phase 1 study showed promising results with a bispecific anti-PD-L1 and anti-transforming
growth factor-β (TGF-β) antibody (M7824). The goal is to inhibit TGF-β, which increases tumor
immunodepression. In addition, inhibition of the TGF-β pathway could increase the activity of anti-
PD-L1. Among 32 patients, 7 had partial response, 6 had tumor stability, and grade III was found among 10
[11]
patients (31.3%). Further development will be interesting to follow .

Monalizumab is a new CPI targeting NKG2A. This is expressed on CD8+ lymphocytes and on NK
lymphocytes. The ligand of NKG2A, human leucocyte antigens (HLA)-E, is overexpressed in HNSCC.