Monalizumab is an immune checkpoint inhibitor targeting Natural Killer Group 2A (NKG2A), expressed on subsets of Natural Killer (NK) and tumor-infiltrating CD8+T cells. NKG2A blockade promotes anti-tumor immunity and may provide additional activity to cetuximab and durvalumab. We report here the safety and efficacy of monalizumab and cetuximab with the addition of durvalumab (cohort 3) in first-line treatment of patients with R/M SCCHN who had not received prior anti-PD-(L)1 mAb or chemotherapy in this setting.
This is a multicenter non-randomized multi-cohort phase 2 trial (NCT02643550) conducted in France and the US. Patients were enrolled regardless of PD-L1 status. Monalizumab (1500 mg Q4W), cetuximab (as per label) and durvalumab (1500 mg Q4W) were administered until disease progression or unacceptable toxicity. The primary endpoint was overall response rate (ORR) assessed per RECIST 1.1. Main secondary endpoints were safety, progression free survival (PFS) and overall survival (OS). Exploratory analyses were performed according to PD-L1 status.
As of August 1, 2021, 40 patients were enrolled in cohort 3. Median age was 65 years (48-91), 12 (30%) patients had oropharynx HPV+ SCCHN and 25 (63%) had a current or prior smoking history. Median follow-up was 16.3 months (4.4-25.7); 13 patients had a confirmed response, ORR=32.5% [95%CI: 20-48], including 3 complete responses. Median time to response was 1.8 months [1.6-3.7], 6/13 responders were still on treatment, with median duration of response not yet reached [7.1-NR], median PFS was 6.9 months [4.4-9.3] and 12 months OS was 59% [45-77]. Results by CPS score will be presented. Grade 3-4 treatment-related adverse events (TRAE) occurred in 19 patients (48%); most frequent events were lipase or amylase increased and dermatitis acneiform (n=4, 4, and 3, respectively); 2 patients (5%) stopped all drugs due to TRAE.
Preliminary data suggest promising antitumor activity of the triplet of monalizumab, cetuximab and durvalumab in first line treatment of R/M SCCHN with an acceptable safety profile.
NCT02643550.
Innate Pharma.
Innate Pharma and AstraZeneca.
D.A. Colevas: Financial Interests, Personal, Writing Engagements: IQVIA RDS, Inc; Financial Interests, Personal, Writing Engagements: ATARA Biotherapeutics. A.T. Pearson: Financial Interests, Personal, Advisory Board: Prelude therapeutics; Financial Interests, Personal, Advisory Board: New Rein LLC. J. Fayette: Financial Interests, Personal, Advisory Board: AstraZeneca; Financial Interests, Personal, Advisory Board: Innate Pharma; Financial Interests, Personal, Advisory Board: Bristol Myers Squibb; Financial Interests, Personal, Advisory Board: Merck Serono; Financial Interests, Personal, Advisory Board: MSD; Financial Interests, Personal, Advisory Board: Roche; Other, Institutional, Research Grant: Seagens; Non-Financial Interests, Personal and Institutional, Principal Investigator: AstraZeneca. J.R. Bauman: Financial Interests, Personal, Advisory Board: AstraZeneca. D.R. Adkins: Financial Interests, Personal and Institutional, Principal Investigator: Innate Pharma; Financial Interests, Institutional, Research Grant: AstraZeneca. D.B. Marie, S.L. Cornen, P. André, F. Carrette, F. Rotolo, A. Boyer Chammard: Financial Interests, Personal, Full or part-time Employment: Innate Pharma. R.B. Cohen: Financial Interests, Personal, Advisory Board: Innate Pharma; Financial Interests, Personal, Advisory Board: AstraZeneca; Other, Personal and Institutional, Principal Investigator: AstraZeneca. All other authors have declared no conflicts of interest.