A phase II study of monalizumab and durvalumab in patients with recurrent/metastatic squamous cell carcinoma of the head and neck: results of the I2 cohort of the EORTC-HNCG-1559 trial (UPSTREAM).
(2025) ESMO Open — Vol. 10, n° 5, p. 104554 (2025)
Files
GalotRESMOOpen2025.pdf
Open Access - Adobe PDF
- 649.11 KB
Details
- Authors
- Abstract
- Monalizumab (M), targeting the natural killer group 2A (NKG2A) receptor, has limited activity as monotherapy in recurrent/metastatic (R/M) squamous cell carcinoma of the head and neck (SCCHN). Preliminary data of M and durvalumab (D) have shown encouraging activity in other tumor types. The UPSTREAM trial was an umbrella trial of targeted therapies and immunotherapy for R/M SCCHN. The immunotherapy 2 (I2) cohort was a phase II, randomized, open-label substudy evaluating the efficacy of D + M versus physician's choice (control). Patients non-eligible for the biomarker-driven cohorts and pretreated with PD(L)1, were included in the I2 cohort. The primary endpoint was the objective response rate (RECIST version 1.1) during the first 16 weeks. Sixty-six patients with R/M SCCHN were included in the I2 cohort, of whom 60 were assessable (D + M: n = 42, control: n = 18): median age 62 years; 87% with two or three previous lines of treatment. In the D + M arm, one partial response (PR) was recorded, and stable disease (SD) was observed in 11 (26%). One PR was reported in the control arm and SD in 8 (44%). The median progression-free survival (PFS) was 2.0 and 3.1 months in the D + M arm and control arm, respectively. The median overall survival (OS) was 4.3 months (95% confidence interval 3.3-8.9 months) and 8.0 months (95% confidence interval 3.1-14.9 months) in the D + M and control arms, respectively. In the D + M arm, 4 (9%) patients reported grade ≥3 treatment-related adverse events. The I2 substudy failed to demonstrate an activity of D + M in heavily pretreated patients with SCCHN previously exposed to anti-PD(L)1. No benefit was seen in PFS and OS.
- Affiliations
Citations
Galot, R., Le Tourneau, C., Licitra, L., Guigay, J., Kong, A., Tinhofer, I., Even, C., Daste, A., Henry, S., Borel, C., Abdeddaim, C., Seront, E., Prevost, J. B., Rutten, A., Saada-Bouzid, E., Rolland, F., Bonomo, P., Rasschaert, M., Dirix, L., et al. (2025). A phase II study of monalizumab and durvalumab in patients with recurrent/metastatic squamous cell carcinoma of the head and neck: results of the I2 cohort of the EORTC-HNCG-1559 trial (UPSTREAM). ESMO Open, 10(5), 104554. https://doi.org/10.1016/j.esmoop.2025.104554 (Original work published 2025)