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Poster Display session 3

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)

Date

30 Sep 2019

Session

Poster Display session 3

Topics

Immunotherapy

Tumour Site

Non-Small Cell Lung Cancer

Presenters

Keisuke Kirita

Citation

Annals of Oncology (2019) 30 (suppl_5): v475-v532. 10.1093/annonc/mdz253

Authors

K. Kirita1, E. Sugiyama2, Y. Togashi2, H. UDAGAWA1, T. Irie2, S. Iida3, M. Nakamoto3, S. Nomura3, T. Ikeda1, Y. Zenke1, S. Matsumoto1, K. Yoh1, S. Niho1, A. Sato3, H. Nishikawa2, K. Goto1

Author affiliations

  • 1 Department Of Thoracic Oncology, National Cancer Center Hospital East, 277-8577 - Kashiwa/JP
  • 2 Division Of Center Immunology, National Cancer Center Hospital East, 277-8577 - Kashiwa/JP
  • 3 Clinical Research Support Office, National Cancer Center Hospital East, 277-8577 - Kashiwa/JP

Resources

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Abstract 1707

Background

While atezolizumab, an anti-PD-L1 monoclonal antibody, is clinically effective against non-small cell lung cancer (NSCLC), its immunological effects on the tumor microenvironment (TME) have not been fully clarified.

Methods

For the biomarker analyses, tumor samples were obtained at baseline, 6 weeks after the initiation of therapy, and/or at the end of therapy. Tumor-infiltrating lymphocytes (TILs) were extracted from those tumor specimens and were subjected to flow cytometry and/or CyTOF for detailed immune profiling.

Results

Twenty-seven eligible patients were analyzed in this trial. The preliminary efficacy results showed an overall RR of 19%, a DCR of 63%, and a median PFS of 4.1 months. To elucidate biomarkers, we compared the immune profiling results between 8 responders (CR, PR, or SD ≥ 6 weeks) and 18 non-responders (SD < 6 weeks or PD). There was no significant difference in the frequency of CD8+ T cells (42.6%±5.3% vs. 38.6%±3.5%, P = 0.53) or that of CD45RA-FoxP3highCD4+ regulatory T cells (Tregs) (14.6%±3.9% vs. 15.4%±2.1%, P = 0.85) at baseline between responders and non-responders. In the responders, PD-1 expression by CD8+TILs was significantly higher than in the non-responders (51.7%±4.7% vs. 25.1%±3.6%, P < 0.01). In addition, PD-1 expression by CD8+TILs increased after atezolizumab therapy regardless of the efficacy of this treatment (P < 0.01), whereas that by Tregs in TILs was comparable (P = 0.76). In addition, we conducted genomic analysis, molecular expression assessment and CyTOF profiling to detect biomarker for atezolizumab.

Conclusions

PD-1 expression by CD8+TILs could be a predictive biomarker for the efficacy of PD-1/PD-L1 blockade therapies. Atezolizumab increased PD-1 expression by CD8+T cells but not by Treg cells in TILs, suggesting that atezolizumab can activate CD8+T cells but not Treg cells in the TME.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

National Cancer Center Hospital.

Funding

Chugai Pharma.

Disclosure

K. Kirita: Honoraria (self), Research grant / Funding (institution): Chugai Pharma; Honoraria (self): AstraZeneca; Honoraria (self): Novartis; Honoraria (self), Research grant / Funding (self): Pfizer; Honoraria (self): Boehringer Ingelheim; Honoraria (self), Research grant / Funding (self): MSD Oncology. Y. Togashi: Honoraria (self): Chugai Pharma; Honoraria (self), Advisory / Consultancy, Research grant / Funding (self): Ono Pharmaceutical; Honoraria (self): MSD; Honoraria (self), Advisory / Consultancy, Research grant / Funding (self): AstraZeneca; Honoraria (self), Advisory / Consultancy, Research grant / Funding (self): Brystol-Myers Squibb. H. Udagawa: Honoraria (self), Advisory / Consultancy, Research grant / Funding (self): AbbVie; Honoraria (self), Advisory / Consultancy, Research grant / Funding (self): Boehringer Ingelheim; Honoraria (self): AstraZeneca; Honoraria (self): Chugai Pharma; Honoraria (self): Bristol-Myers Squibb; Honoraria (self): Ono Pharmaceutical; Honoraria (self): Taiho Pharmaceutical; Honoraria (self), Research grant / Funding (self): Daiichi Sankyo; Research grant / Funding (self): Amgen. S. Nomura: Honoraria (self): Taiho Pharmaceutical. Y. Zenke: Honoraria (self): Boehringer Ingelheim; Honoraria (self): Chugai Pharma; Honoraria (self): AstraZeneca; Honoraria (self): Lilly; Honoraria (self): Taiho Pharmaceutical; Honoraria (self): MSD Oncology; Research grant / Funding (institution): Ono Pharmaceutical. S. Matsumoto: Honoraria (self), Research grant / Funding (institution): Ono pharmaceutical; Honoraria (self), Research grant / Funding (institution): Pfizer; Honoraria (self), Research grant / Funding (institution): Bristol-Myers Squibb Japan; Research grant / Funding (institution): Astellas Pharma; Research grant / Funding (institution): AstraZeneca KK; Research grant / Funding (institution): Amgen; Research grant / Funding (institution): Eisai; Research grant / Funding (institution): Kyowa Hakko Kirin; Research grant / Funding (institution): Daiichi Sankyo; Research grant / Funding (institution): Taiho Pharmaceutical; Research grant / Funding (institution): Takeda; Research grant / Funding (institution): Chugai Pharma; Research grant / Funding (institution): Novartis; Research grant / Funding (institution): Lilly; Research grant / Funding (institution): Merck Serono; Research grant / Funding (institution): Riken Genesis; Research grant / Funding (institution): MSD. K. Yoh: Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): AstraZeneca; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): Lilly Japan; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): Chugai Pharma; Honoraria (self): Boehringer Ingelheim; Honoraria (self), Research grant / Funding (institution): Novartis; Honoraria (self), Research grant / Funding (institution): MSD; Honoraria (self), Research grant / Funding (institution): Daiichi Sankyo; Honoraria (self): Kirin Pharmaceuticals; Research grant / Funding (institution): Bayer; Research grant / Funding (institution): Pfizer; Research grant / Funding (institution): Taiho Pharmaceutical; Research grant / Funding (institution): Bristol-Myers Squibb; Research grant / Funding (institution): Ono Pharmaceutical. S. Niho: Honoraria (self), Research grant / Funding (institution): Lilly; Honoraria (self), Research grant / Funding (institution): AstraZeneca; Honoraria (self), Research grant / Funding (institution): MSD; Honoraria (self), Research grant / Funding (institution): Pfizer; Honoraria (self): Taiho Pharmaceutical; Honoraria (self): Bristol-Myers Squibb Japan; Honoraria (self): Ono Pharmaceutival; Research grant / Funding (institution): Merck Serono. A. Sato: Honoraria (self), Research grant / Funding (institution): Sumitomo Dainippon Pharma; Honoraria (self): AstraZeneca; Research grant / Funding (institution): Taiho Pharmaceutical; Research grant / Funding (institution): Boehringer Ingelheim; Research grant / Funding (institution): Bayer; Research grant / Funding (institution): Chugai Pharma; Research grant / Funding (institution): Eisai; Research grant / Funding (institution): MSD; Research grant / Funding (institution): Ono Pharmaceutical; Research grant / Funding (institution): Takeda; Research grant / Funding (institution): Oncolys BioPharma; Research grant / Funding (institution): Aspyerian Therapeutics. H. Nishikawa: Honoraria (self), Advisory / Consultancy, Research grant / Funding (self): Ono Pharmaceutical; Honoraria (self), Research grant / Funding (self): Bristol-Myers Squibb Japan; Honoraria (self), Research grant / Funding (self): Chugai Pharma; Research grant / Funding (self): BD Biosciences; Research grant / Funding (self): Daiichi Sankyo; Research grant / Funding (self): Kyowa Hakko Kirin; Research grant / Funding (self): Zenyaku Kogyo; Research grant / Funding (self): AstraZeneca; Research grant / Funding (self): Astellas Pharma; Research grant / Funding (self): Taiho Pharmaceutical; Research grant / Funding (self): Asahi Kasei; Research grant / Funding (self): Sysmex. K. Goto: Honoraria (self), Advisory / Consultancy: Otsuka; Honoraria (self), Research grant / Funding (self): Bristol-Myers Squibb; Honoraria (self), Research grant / Funding (self): AstraZeneca; Honoraria (self), Research grant / Funding (self): Pfizer; Honoraria (self), Research grant / Funding (self): Chugai Pharma; Honoraria (self), Research grant / Funding (self): Taiho Pharmaceutical; Honoraria (self), Research grant / Funding (self): Ono Pharmaceutical; Honoraria (self), Research grant / Funding (self): Novartis; Honoraria (self), Research grant / Funding (self): Lilly; Honoraria (self), Research grant / Funding (self): Boehringer Ingelheim; Honoraria (self): Quintiles; Honoraria (self), Research grant / Funding (self): Merck Serono; Honoraria (self), Research grant / Funding (self): Life Technologies; Honoraria (self), Research grant / Funding (self): MSD; Honoraria (self): AbbVie; Honoraria (self), Research grant / Funding (self): Riken Genesis; Honoraria (self): Nippon Kayaku; Honoraria (self), Research grant / Funding (self): Takeda; Honoraria (self): SRL Diagnostics; Research grant / Funding (self): Sumitomo Dainippon Pharma. All other authors have declared no conflicts of interest.

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