Abstract 1242
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.
Resources from the same session
3140 - Phase 2 study of olaparib in previously treated advanced solid tumors with homologous recombination repair mutation (HRRm) or homologous recombination repair deficiency (HRD): LYNK-002
Presenter: David Hyman
Session: Poster Display session 3
Resources:
Abstract
2655 - The K-BASKET trial: A prospective phase II biomarker-driven multiple basket trial in Korean solid cancer patients.
Presenter: Seul Kim
Session: Poster Display session 3
Resources:
Abstract
5938 - Cambridge Liquid biopsy “CALIBRATION” study: Can changes in circulating tumour DNA (ctDNA) predict durable tumour responses in patients with advanced oesophageal cancer receiving MEDI4736?
Presenter: Constanza Linossi
Session: Poster Display session 3
Resources:
Abstract
3799 - Validation of a tumour mutational burden workflow on routine histological samples of colorectal cancer and assessment of a cohort with synchronous hepatic metastases
Presenter: Andrea Mafficini
Session: Poster Display session 3
Resources:
Abstract
4647 - Microsatellite Instability Testing and Lynch Syndrome Screening For Colorectal Cancer Patients Through Tumor Sequencing
Presenter: Li Liu
Session: Poster Display session 3
Resources:
Abstract
3231 - "Liquid Withdarw" technique in CT-guided cutting needle lung biopsy: decreased incidence of complications and increased tissue amount for lung cancer molecular testing.
Presenter: Xue Wang
Session: Poster Display session 3
Resources:
Abstract
3282 - WGS Implementation in standard cancer Diagnostics for Every cancer patient (WIDE)
Presenter: Paul Roepman
Session: Poster Display session 3
Resources:
Abstract
5905 - Known and unknown gene fusion detection capabilities of solid tumor laboratories conducting next generation sequencing in 6 countries
Presenter: Steph Finucane
Session: Poster Display session 3
Resources:
Abstract
4238 - Clinical and Analytical Accuracy of a 523 Gene Panel Next-Generation Sequencing (NGS) Assay on Formalin-Fixed Paraffin-Embedded (FFPE) Solid Tumor Samples
Presenter: Ina Deras
Session: Poster Display session 3
Resources:
Abstract
2493 - Methylation analysis of MLH1 using droplet digital PCR and methylation sensitive restriction enzyme.
Presenter: Celine De Rop
Session: Poster Display session 3
Resources:
Abstract