Abstract 2607
Background
In head and neck squamous cell cancer (HNSCC) a valid predictive parameter for the efficacy of immune-checkpoint inhibitors is still missing especially in locally advanced stages.
Methods
In the phase II CheckRad-CD8 trial unselected patients with HNSCC stage III-IVB receive one cycle of induction chemo-immunotherapy with cisplatin (30mg/m² d1-3)/ docetaxel (75mg/m² d1) plus durvalumab (1500mg absolute d5)/ tremelimumab(75mg absolute d5). Intra- and peritumoral CD8+ cytotoxic T-cells are assessed before and after the induction chemo-immunotherapy. Patients with CD8+ T-cell increase after induction chemo-immunotherapy enter radio-immunotherapy, patients without CD8+ T-cell increase enter radio-chemotherapy. This interim analysis including immunophenotyping of whole blood was performed after 10 patients had completed the re-evaluation after induction chemo-immunotherapy.
Results
6 patients with oropharyngeal, 2 patients with hypopharyngeal and 2 patients with supraglottic laryngeal cancer were included. The mean pre-treatment intratumoral CD8 density was 1094 CD8+ cells/mm². 8 of 10 patients had a pathological complete response of their primary tumor defined by complete absence of remaining tumor cells in re-biopsies after induction treatment. The other two patients showed an average intratumoral increase from 227 CD8+ cells/mm² to 1074 CD8+ cells/mm². According to RECIST 1.1 criteria 6 patients had a partial response (PR), 3 patients a stable disease (SD), 1 patient was not evaluable. Grade III-IV toxicity included one case of hepatitis and one infectious diarrhea. Detailed immunophenotyping revealed a trend of slight reduction of CD8+ T-cells in the peripheral blood of patients with initially lower numbers of intratumoral CD8+ T-cells. The early activation marker CD69 is increased on T-cells and PD-1 on T-helper cells after induction treatment.
Conclusions
These preliminary results suggest a promising response to single cycle induction treatment with cisplatin/ docetaxel plus durvalumab/ tremelimumab in unselected HNSCC patients. Furthermore, they show an induction of an immune response in both in the tumor tissue and the peripheral blood.
Clinical trial identification
NCT03426657.
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
AstraZeneca.
Disclosure
M. Hecht: Research grant / Funding (institution): AstraZeneca; Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: MSD. A. Gostian: Advisory / Consultancy: test. M. Eckstein: Honoraria (self), Advisory / Consultancy: AstraZeneca; Advisory / Consultancy, Research grant / Funding (institution): Janssen-Cilag/Johnson&Johnson; Honoraria (self): Astellas; Honoraria (self): Roche. M.G. Hautmann: Honoraria (self): AstraZeneca. S. Laban: Honoraria (self), Advisory / Consultancy: MSD; Honoraria (self), Advisory / Consultancy: BMS; Honoraria (self), Advisory / Consultancy: AstraZeneca; Honoraria (self): Merck Serono. A. Hartmann: Honoraria (self), Advisory / Consultancy: BMS; Honoraria (self), Advisory / Consultancy: MSD; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): Roche; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): Cepheid; Honoraria (self), Advisory / Consultancy: AstraZeneca; Honoraria (self), Advisory / Consultancy: Boehringer Ingelheim; Honoraria (self), Advisory / Consultancy: AbbVie; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): Janssen; Advisory / Consultancy, Research grant / Funding (institution): NanoString; Advisory / Consultancy, Research grant / Funding (institution): Illumina; Advisory / Consultancy: Quiagen; Advisory / Consultancy, Research grant / Funding (institution): Biontech; Advisory / Consultancy: 3D Histotech. U. Gaipl: Research grant / Funding (institution): AstraZeneca; Research grant / Funding (institution): MSD. R. Fietkau: Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): Merck Serono; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): AstraZeneca; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): Novocure; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): Brainlab; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): Fresenius Kabi; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): BMS; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): MSD. All other authors have declared no conflicts of interest.
Resources from the same session
4692 - Immune cell biomarkers on neo-adjuvant chemo-immunotherapy treatment for resectable stage IIIA NSCLC patients
Presenter: Raquel Laza-Briviesca
Session: Poster Display session 3
Resources:
Abstract
1707 - Clinical utility of precision immunoprofiling and monitoring of the tumor microenvironment using flow cytometry and CyTOF in patients with advanced NSCLC treated with atezolizumab: results from a phase II study for biomarker analysis (EPOC1702)
Presenter: Keisuke Kirita
Session: Poster Display session 3
Resources:
Abstract
3594 - Tumor mutation burden (TMB), PD-L1, IFN-γ signaling identify subgroups of patients (pts) who benefit from durvalumab (D, anti-PDL1) or D and tremelimumab (T, anti-CTLA4) treatment in urothelial bladder cancer (UC)
Presenter: Christophe Massard
Session: Poster Display session 3
Resources:
Abstract
744 - The decrease of TMB, TNB and HLA expression are the Mechanism of Drug Resistance of NSCLC to immunosuppressive PD-1/PD-l1.
Presenter: Sheng Yu
Session: Poster Display session 3
Resources:
Abstract
2350 - Eosinophilia during treatment of immune checkpoint inhibitors (ICIs) predicts succeeding onset of immune-related adverse events (irAEs)
Presenter: Rika Kizawa
Session: Poster Display session 3
Resources:
Abstract
5930 - A transcriptomic immunologic signature predicts favorable outcome in neoadjuvant chemotherapy treated triple negative breast tumors.
Presenter: Javier Pérez-peña
Session: Poster Display session 3
Resources:
Abstract
6127 - Alterations of TMB and TCR repertoires during Chemotherapy in East Asian lung cancer patients without TKI-related driver gene mutations
Presenter: Lele Song
Session: Poster Display session 3
Resources:
Abstract
1310 - Association of SCFA in gut microbiome and clinical response in solid cancer patients treated with andi-PD-1 antibody.
Presenter: Motoo Nomura
Session: Poster Display session 3
Resources:
Abstract
2286 - Extracellular matrix and tissue derived metabolites in a liquid biopsy identifies endotypes of metastatic melanoma patients with differential response to immune checkpoint inhibitor treatment
Presenter: Nicholas Willumsen
Session: Poster Display session 3
Resources:
Abstract
4107 - Pathologic scoring of pre-treatment H&E biopsies predicts overall survival in patients with metastatic clear cell renal cell carcinoma receiving nivolumab monotherapy
Presenter: Julie Stein
Session: Poster Display session 3
Resources:
Abstract