Major pathological response with neoadjuvant immunotherapy in head and neck squamous cell carcinoma

January 2022 Cancer trials Nalinee Pathak

Combination neoadjuvant immunotherapy provided favorable outcomes in head and neck squamous cell carcinoma (HNSCC) patients. Results from the IMCISION trial were recently published in the journal Nature Communications.

Phase1/II study

A non-randomized phase 1/2 study enrolled 32 (63% males) with HNSCC who received two immune checkpoint inhibitors (ICI) doses in weeks one and three. In phase 1b, patients in arm A (n=6) were treated with nivolumab (nivo) and a combination of nivo + single dose of ipilimumab (n=26, 6 in phase Ib, and 20 in phase IIa) in arm B before surgery. The study’s two primary endpoints were feasibility to resect before week 6 (phase 1b) and primary tumor pathological response (PR) (phase IIa).


The PR (defined as % change in primary tumour viable tumour cell percentage from baseline biopsy to on-treatment resection) was available for evaluation in 29 (out of 32) patients. The phase IIa primary endpoint threshold was met (10%) as a higher major PR (MPR-90-100% response) was observed in 35% (6/17 phase IIa and 8/23 whole trial) of the patients administered combination ICIs in comparison to those treated with nivo monotherapy (17%, 1/6). During postsurgical follow up of two years, none of the patients with MPR developed recurrent HNSCCs. Additionally, a decrease in hypoxia RNA signature and an AID/APOBEC-associated mutational profile was seen in these patients. Finally, Immune-related adverse events were reported in 33% (2/6) and 38% (10/26) patients treated with nivo and combination therapy, respectively.


The results of IMCISION demonstrate that neoadjuvant ICI combination is effective and safe for HNSCC patients before surgery.  Future trials are needed for evaluating the efficacy of combination ICIs in HNSCC patients.


Vos JL, Elbers JBW, Krijgsman O, et al. Neoadjuvant immunotherapy with nivolumab and ipilimumab induces major pathological responses in patients with head and neck squamous cell carcinoma. Nat Commun. 2021 Dec 22;12(1):7348. doi: 10.1038/s41467-021-26472-9. PMID: 34937871.