A phase II study of monalizumab and durvalumab in patients with recurrent/metastatic(RM) squamous cell carcinoma of the head and neck (SCCHN): result s of the I2 cohort of the EORTC-HNCG-1559 trial (UPSTREAM.

Galot, Rachel;et.al.
(2023) ESMO 2023 — Location: Madrid (20.October.2023)

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Background Monalizumab (mona), a IgG4 Ab targeting the NKG2A receptor, has limited activity as monotherapy in RM SCCHN. Targeting the NKG2A-HLA-E pathway with PD(L)1 blockade improved tumor control in mice. Preliminary data of mona and durvalumab (durva), have shown encouraging activity in pretreated MSS colorectal cancer. Methods The UPSTREAM trial is an umbrella trial of targeted therapies and immunotherapy for RM SCCHN (post platinum, ECOG 0-1). The immunotherapy 2 (I2) cohort was a phase II, randomized, open label substudy evaluating the efficacy of the combination of durva (iv, 1500mg Q4W) and mona (iv, 750mg Q2W or Q4W) (D+M) vs physician’s choice (control, ctrl) (2:1 ratio). Pts non-eligible for the biomarker-driven cohorts and pretreated with PD(L)1, were included in the I2 cohort. The primary endpoint was objective response rate (RECISTv1.1) during the first 16 weeks (2-stage Simon design applied to the D+M arm, H1 15%, H0 3%, 1-sided α 10%, power 90%). Secondary endpoints included response duration, toxicity, PFS, and OS. Results 66 RM SCCHN pts were included in the I2 cohort (D+M: n=45, ctrl: n=21). 61 pts were evaluable (D+M: n=43, ctrl: n=18): median age 62 yrs; oral cavity 20%, oropharynx 39%, hypopharynx 20%, larynx 21%; 87% with 2 or 3 previous lines. In D+M 1 partial response (PR) was recorded and stable disease (SD) was observed in 11 pts (26%). 1 PR was reported in the ctrl arm and SD in 8 (44%). The median PFS was 2.0 mo (95% CI: 1.8-2.4) and 3.1 mo (95% CI: 1.9-3.9) in the D+M arm and ctrl arm, respectively. The median OS was 4.4 mo (95% CI: 3.3-9.2) and 8.0 mo (95% CI: 3.1-14.9) in the D+M and ctrl arm, respectively. In the D+M arm, 4 pts (9%) reported grade  3 treatment-related adverse events. Conclusions The substudy of mona and durva did not meet its primary objective. No benefit was seen in PFS and OS. These are preliminary results, definitive results will be presented at the congress. ClinicalTrials.gov: NCT03088059
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Galot, R., & et al. (2023). A phase II study of monalizumab and durvalumab in patients with recurrent/metastatic(RM) squamous cell carcinoma of the head and neck (SCCHN): result s of the I2 cohort of the EORTC-HNCG-1559 trial (UPSTREAM. ESMO 2023, Madrid. https://hdl.handle.net/2078.5/25197