Findings from the phase 1/2 IPH2201-203 trial support the statement that monalizumab, cetuximab, and durvalumab show promising activity in patients with recurrent squamous cell carcinoma of the head and neck.
The addition of the antiNKG2A antibody monalizumab (formerly IPH2201) to cetuximab (Erbitux) and durvalumab (Imfinzi) showed significant disease control in patients with recurrent or metastatic squamous cell carcinoma of the head and neck (SCCHN), according to findings from a cohort of the phase 1/2 IPH2201-203 trial (NCT02643550).1 Results presented during the European Society for Medical Oncology ImmunoOncology Congress 2021 demonstrated that 35 of 40 participants achieved a response rate of 87.5% in the cohort.
“These data support the statement that monalizumab, cetuximab, and durvalumab show promising activity in these patients with recurrent squamous cell carcinoma of the head and neck, [and] it’s particularly noteworthy that this is a chemotherapy-free regimen with a very low AE [adverse event] profi le,” said A. Dimitrios Colevas, MD, professor of medicine, otolaryngology, and radiation oncology at Stanford Cancer Center, and member of Stanford Cancer Institute in California.
Monalizumab is a first-in-class checkpoint inhibitor targeting the CD94/NKG2A receptor. NKG2A is expressed on subsets of natural killer cells and tumor-infi ltrating CD8-positive T cells, and inhibiting leads to innate immunity and cytotoxicity further enhanced by cetuximab. The single-arm, multicenter, multicohort IPH2201- 203 trial was the fi rst study to explore the triplet combination. The trial consisted of a dose escalation portion, followed by 3 expansion cohorts for patients with SCCHN. Cohort 3 added monalizumab.
In this cohort, patients with recurrent/metastatic SCCHN were enrolled who had no prior systemic therapy in this setting. Participants were enrolled regardless of their PD-L1 or human papillomavirus (HPV) status.
The primary end point of the cohort was ORR by RECIST criteria, and the key secondary end points included safety, duration of response (DOR), progression-free survival (PFS), and overall survival (OS).
The confi rmed ORR was 32.5% (95% CI, 20%- 48%). When including unconfi rmed responses, the rate went up to 50% (95% CI, 35%-65%). Complete responses were reported in 3 patients, partial responses in 10, and stable disease in 22. Four patients experienced progressive disease and 1 had an early death and was not evaluable. “There were quite a few responders who had very deep response, even some with complete response,” Colevas said. “These responses were not short-lived.”
At a median follow-up of 16.3 months (range, 4.4-25.7), the median PFS was 6.9 months (95% CI, 4.4-9.3) and the median OS was 15 months (95% CI, 11.4–not available [NA]). At 12 months, the OS rate was 58.6% (95% CI, 45%-77%) and 7 of 13 patients had ongoing response, with the longest lasting 19.5 months. The median DOR was NA (95% CI, 7.1-NA).
In previous results from another cohort of the study, treatment with the doublet of monalizumab and cetuximab demonstrated promising activity in patients with recurrent or metastatic SCCHN. In 40 treated patients with prior immunotherapy treatment, the objective response rate (ORR) was 20% (95% CI, 10.5%-34.8%).2
An exploratory analysis was performed through response by PD-L1 CPS levels, and responses were seen in patients with both positive and negative PD-L1 levels. However, Colevas cautioned that as there were small subsets of patients, especially those with CPS less than 1, the results should be interpreted with caution and are not actionable for selecting patients who would benefit from this regimen.
Treatment-emergent AEs were reported in all patients, with the most common, of any grade, being dermatitis acneiform, paronychia, fatigue, pruritus, and hypomagnesaemia. Grade 3 or higher events were observed in 72% of patients, with 48% being drug related. AEs led to discontinuation of a drug in 12% of patients and discontinuation of all 3 drugs in 5%. AEs led to death in 8%, but none of these events were considered related to treatment.
Colevas said there were no new safety signals identified in the preliminary results of the cohort. He concluded that these data support further evaluation of the triplet regimen of monalizumab, cetuximab, and durvalumab in the SCCHN population.
1. Colevas AD, Misiukiewicz K, Pearson TA, et al. Monalizumab, cetuximab and durvalumab in fi rst line treatment of recurrent or metastatic squamous cell carcinoma of the head and neck (R/M SCCHN): a phase 2 trial. Presented at: ESMO Immuno-Oncology Congress 2021; December 8-11, 2021; virtual. Abstract 123MO. https://bit.ly/33G1Ssf
2. Cohen RB, Bauman JR, Salas S, et al. Combination of monalizumab and cetuximab in recurrent or metastatic head and neck cancer patients previously treated with platinum-based chemotherapy and PD-(L)1 inhibitors. J Clin Oncol. 2020;38(suppl 15):6516. doi:10.1200/JCO.2020.38.15_suppl.6516