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)

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^-FoxP3^highCD4⁺ 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.