935P - A phase II study of monalizumab and durvalumab in patients with recurrent/metastatic (RM) squamous cell carcinoma of the head and neck (SCCHN): Results of the I2 cohort of the EORTC-HNCG-1559 trial (UPSTREAM)

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.

Clinical trial identification

NCT03088059.

Editorial acknowledgement

Legal entity responsible for the study

EORTC.

Funding

Innate Pharma and AstraZeneca.

Disclosure

R. Galot: Other, Other, Travel expenses: Merck. C. Le Tourneau: Financial Interests, Personal, Advisory Board: BMS, MSD, Merck Serono, Nanobiotix, Roche, Rakuten, Seattle Genetics, GSK, Celgene, ALX Oncology, Exscientia. L.F.L. Licitra: Financial Interests, Personal, Advisory Board, for expert opinion in advisory boards: AstraZeneca, Bayer, BMS, Eisai, MSD, Merck–Serono, Boehringer Ingelheim, Hoffmann-La Roche Ltd, Novartis, Roche, Debiopharm International SA, Sobi, Incyte Biosciences Italy srl, Doxa Pharma srl, Amgen, Nanobiotics e GSK.; Financial Interests, Institutional, Research Grant, Funds received by my institution for clinical studies and research activities in which I am involved: AstraZeneca, BMS, Boehringer Ingelheim, Celgene International, Eisai, Exelixis, Debiopharm International SA, Hoffmann-La Roche ltd, IRX Therapeutics, Medpace, Merck–Serono, Merck Healthcare KGaA, MSD, Novartis, Pfizer, Roche, Buran. C. Even: Financial Interests, Personal, Advisory Board: BMS, MSD, Innate Pharma, Merck Serono; Financial Interests, Institutional, Advisory Board: F Star Therapeutics, Novartis, Elevar; Financial Interests, Institutional, Local PI: BMS, AstraZeneca, ISA pharmaceutics, MSD, Debiopharma, Ayala, Gilead; Financial Interests, Institutional, Coordinating PI: BMS, Novartis, sanofi. A. Daste: Financial Interests, Personal, Advisory Board: Merck, BMS, MSD. S. Henry: Financial Interests, Personal, Advisory Board: AstraZeneca, BMS, Gilead Sciences, GSK, Merck, MSD Oncology, Novartis; Financial Interests, Personal, Other, consulting: Sanofi; Financial Interests, Personal, Royalties: AstraZeneca, BMSi, GSK, Gilead Sciences, Merck, Novartis, Sanofi, Teva; Non-Financial Interests, Personal, Other, asco 2023 virtual inscription: Teva. C. Borel: Financial Interests, Personal, Invited Speaker: AstraZeneca, BMS, Merck Serono, MSD; Financial Interests, Personal, Advisory Board: AstraZeneca, Merck Serono, MSD. F. Rolland: Financial Interests, Personal, Advisory Board: Pfizer, Eisai, MSD, Merck Serono; Financial Interests, Institutional, Coordinating PI: Exelixis; Financial Interests, Institutional, Local PI: BMS, IPSEN. J. Machiels: Financial Interests, Institutional, Advisory Board: novartis, MSD, Pfizer, Roche, Debio, AstraZeneca, Innate, Nanobiotix, Bayer, Merck-Serono, Boerhinger-Ingelheim, BMS, Pfizer, Cue Pharma, Incyte, Janssen, Johnson & Johnson, ALX Oncology, F-star, nektar, F-star, Seagen, astellas, genmab; Financial Interests, Institutional, Other, Travel expense: Gilead, MSD, sanofi; Financial Interests, Institutional, Steering Committee Member: AstraZeneca, MSD; Financial Interests, Institutional, Coordinating PI: MSD, iTeos, eTheRNA; Financial Interests, Institutional, Local PI: Pfizer, Ceylad, MSD, Novartis, Kura, Roche, Lilly, Boehringer, Sanofi-Aventis, Incyte, Bayer, Merck - Serono, Janssen, Johnson & Johnson, Amgen, AbbVie, GalxoSmithKline; Non-Financial Interests, Leadership Role, Chair: EORTC head and neck group. All other authors have declared no conflicts of interest.