1242 - Monalizumab in combination with cetuximab in patients (pts) with recurrent or metastatic (R/M) head and neck cancer (SCCHN) previously treated or not with PD-(L)1 inhibitors (IO): 1-year survival data.

Background

Monalizumab is a first in class immune checkpoint inhibitor targeting Natural Killer Group 2A (NKG2A), which is expressed as a heterodimer with CD94 on subsets of Natural Killer (NK), γδ T and tumor-infiltrating CD8⁺ T cells (André et al. Cell 2018). The NKG2A ligand, HLA-E, is upregulated in cancer, including SCCHN. NKG2A blockade promotes innate anti-tumor immunity mediated by NK and CD8⁺ T cells and enhances human NK cell antibody-dependent cell-mediated cytotoxicity (ADCC) induced by cetuximab. This dual targeting could provide greater antitumor activity than cetuximab alone.

Methods

The multicenter phase II trial tested the combination of monalizumab and cetuximab in pts with R/M SCCHN. Pts received monalizumab 10 mg/kg q2weeks and cetuximab according to the label until disease progression or unacceptable toxicity. Pts were required to be progressing after platinum-based chemotherapy and to have received ≤2 prior lines of therapy in the R/M setting. Previous treatment with IO was allowed. The primary endpoint was Overall Response Rate (ORR) per RECIST.

Results

All 40 pts received prior platinum-based chemotherapy, 18 (45%) prior IO and 5 (13%) prior cetuximab. ORR was 27.5% [95% confidence interval: 16-43] with 11 confirmed responses (1 complete + 10 partial) observed in both IO naive 36% [20-57] and IO pretreated pts 17% [6-39]. As of April 17, 2019, with a median follow-up of 17 months (mo), in all pts, IO naïve and IO pretreated pts respectively, median duration of response was 5.6, 5.3 and 5.6 mo, PFS was 4.5, 3.9 and 5.1 mo and OS was 8.3, 7.8 and 12.8 mo. The 12 mo OS estimate is 44% [31-63]. No new safety signal emerged. Pre and post treatment tumor biopsies were collected and RNA seq analyses are ongoing.

Conclusions

In a cohort of 40 patients of heavily pretreated SCCHN patients, monalizumab and cetuximab combination demonstrated high response rate, good duration of response, and promising PFS and OS as well as good safety profile. An additional R/M SCCHN cohort of 40 patients who received both platinum-based chemotherapy and IO is being enrolled in this study.

Clinical trial identification

NCT02643550.

Editorial acknowledgement

Legal entity responsible for the study

Innate Pharma.

Funding

Innate Pharma.

Disclosure

R.B. Cohen: Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): Innate Pharma; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): Genocea; Research grant / Funding (institution): Celldex; Research grant / Funding (institution): Macrogenics; Research grant / Funding (institution): Merck. M.R. Posner: Advisory / Consultancy: Merck; Advisory / Consultancy: Cel-Sci; Shareholder / Stockholder / Stock options: Promedior; Licensing / Royalties: Bet Isreal-Deaconess Médical Centre, Arizona Stat. J.R. Bauman: Advisory / Consultancy: Pfizer; Advisory / Consultancy: Bayer. C. Even: Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): Innate Pharma; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): Genocea; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: Heat; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Alkermes; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): Arrys; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Takeda; Honoraria (self), Advisory / Consultancy: Cantargia; Research grant / Funding (institution): Celldex; Research grant / Funding (institution): Xencor. E. Saada-Bouzid: Advisory / Consultancy: AstraZeneca. T. Seiwert: Honoraria (self): Aduro biotech; Honoraria (self): AstraZeneca; Honoraria (self): Bayer; Honoraria (self), Research grant / Funding (institution): BMS; Honoraria (self): Celgene; Honoraria (self): Innate; Honoraria (self): Loxo Oncology; Honoraria (self), Research grant / Funding (institution): Merck; Honoraria (self): Nanobiotix; Research grant / Funding (institution): Jounce. F. Calmels: Shareholder / Stockholder / Stock options, Full / Part-time employment: Innate Pharma. R. Zerbib: Shareholder / Stockholder / Stock options, Full / Part-time employment: Innate Pharma. P. André: Shareholder / Stockholder / Stock options, Full / Part-time employment: Innate Pharma. A. Boyer-Chammard: Shareholder / Stockholder / Stock options, Full / Part-time employment: Innate Pharma. J. Fayette: Honoraria (self), Advisory / Consultancy, Research grant / Funding (self), Travel / Accommodation / Expenses: AstraZeneca; Honoraria (self), Advisory / Consultancy, Research grant / Funding (self), Travel / Accommodation / Expenses: BMS; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: MSD; Honoraria (self), Advisory / Consultancy: Merck Serono; Honoraria (self), Advisory / Consultancy: Innate Pharma; Honoraria (self), Advisory / Consultancy: Biogen. All other authors have declared no conflicts of interest.