Plasma Protein Analysis for Biomarker Discovery in Lung Cancer Treated With Atezolizumab Combination Therapy in J-TAIL-2

Sep 23, 2026

Uploaded by Ben

J-TAIL-2 evaluated atezolizumab, an anti–PD-L1 agent, combined with chemotherapy in Japanese practice for non-small cell lung cancer and extensive-stage small cell lung cancer, showing outcomes comparable with Phase 3 trials. While PD-L1 may predict benefit in certain contexts, additional minimally invasive, blood-based biomarkers are required. This exploratory biomarker study analyzed 359 patients and assessed ~560 cancer- or immune-related proteins in plasma using Proximity Extension Assay at three timepoints. Protein associations were linked to clinical outcomes, identifying regimen- and subgroup-dependent immune signals relevant to efficacy and immune-related adverse events.

LanguageEnglish

CategoryHealthcare

FormatPDF

Pages13

Reading Time33 min

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Introduction

Plasma protein biomarker analysis workflow

Protein associations with clinical outcomes and irAEs

Trial design and patient cohorts

Cancer Science ORIGINAL ARTICLE OPEN ACCESS Drug Discovery and Delivery Plasma Protein Analysis for Biomarker Discovery in Lung Cancer Treated With Atezolizumab Combination Therapy in J-TAIL-2 Yasushi Goto1 | Makoto Nishio2 | Kadoaki Ohashi3 | Atsushi Osoegawa4 | Eiki Kikuchi5 | Hideharu Kimura6 | Junichi Shimizu7 | Eisaku Miyauchi8 | Hiroshige Yoshioka9,10 | Ichiro Yoshino11,12 | Toshihiro Misumi13 | Yasutaka Watanabe14 | Nobuyuki Katakami15 | Akira Kisohara16 | Masafumi Yamaguchi17 | Hirotaka Kuroki18 | Masamichi Sugimoto18 | Hisao Ashimura18 | Misa Tanaka18 | Akihiko Gemma19 1Department of Thoracic Oncology, National Cancer Center Hospital, Tokyo, Japan | 2Department of Thoracic Medical Oncology, Cancer Institute Hospital of Japanese Foundation for Cancer Research, Tokyo, Japan | 3Department of Respiratory Medicine, Okayama University Hospital, Okayama, Japan | 4Department of Thoracic and Breast Surgery, Oita University Faculty of Medicine, Yufu, Japan | 5Department of Respiratory Medicine, Faculty of Medicine, Hokkaido University, Sapporo, Japan | 6Department of Respiratory Medicine, Kanazawa University Hospital, Kanazawa, Japan | 7Department of Thoracic Oncology, Aichi Cancer Center Hospital, Nagoya, Japan | 8Department of Respiratory Medicine, Tohoku University Hospital, Sendai, Japan | 9Department of Thoracic Oncology, Kansai Medical University, Hirakata, Japan | 10Department of Respiratory Medicine and Clinical Immunology, Dokkyo Medical University Saitama Medical Center, Koshigaya, Japan | 11Department of Thoracic Surgery, International University of Health and Welfare Narita Hospital, Narita, Japan | 12Department of General Thoracic Surgery, Chiba University Hospital, Chiba, Japan | 13Department of Data Science, National Cancer Center Hospital East, Kashiwa, Japan | 14Department of Thoracic Oncology, Saitama Cancer Center, Saitama, Japan | 15Department of Pulmonary Medicine and Medical Oncology, Takarazuka City Hospital, Takarazuka, Japan | 16Department of Respiratory Medicine, Kasukabe Medical Center, Kasukabe, Japan | 17Department of Thoracic Oncology, NHO Kyushu Cancer Center, Fukuoka, Japan | 18Chugai Pharmaceutical Co. , Ltd., Tokyo, Japan | 19Nippon Medical School, Tokyo, Japan Correspondence: Akihiko Gemma ([agemma@nms.ac.jp](agemma@nms.ac.jp)) Received: 6 October 2025 | Revised: 11 March 2026 | Accepted: 17 March 2026 Keywords: atezolizumab | biomarker | non-small cell lung cancer | plasma protein | small cell lung cancer ABSTRACT J-TAIL-2 evaluated the efficacy and safety of atezolizumab, an anti–programmed death-ligand 1 (PD-L1), plus chemotherapy in patients with non-small cell lung cancer (NSCLC) and extensive-stage small cell lung cancer (ES-SCLC) in Japanese clinical practice, demonstrating comparable outcomes to those in the corresponding Phase 3 trials. Although PD-L1 expression is predictive of atezolizumab efficacy in some settings, additional minimally invasive, blood-based biomarkers are needed. This exploratory biomarker study included 359 J-TAIL-2 patients. The NSCLC cohort received atezolizumab combined with carboplatin and nab-paclitaxel (CnP, n = 42), cisplatin/carboplatin and pemetrexed (n = 72), or bevacizumab plus carboplatin and paclitaxel (bev + CP, n = 135) . The ES-SCLC cohort received atezolizumab plus carboplatin and etoposide (n = 100) . Approximately 560 cancer- or immune-related proteins were evaluated using the Proximity Extension Assay from blood plasma collected at three timepoints: baseline, before the second atezolizumab dose, and at the onset of immune-related | Abbreviations: AE, adverse event; Atezo + bev + CP, atezolizumab plus bevacizumab plus carboplatin and paclitaxel; Atezo + CE, atezolizumab plus carboplatin and etoposide; Atezo + CnP, atezolizumab plus carboplatin and nab-paclitaxel; Atezo + PP, atezolizumab plus carboplatin or cisplatin plus pemetrexed; CI, confidence interval; CnP, carboplatin and nab-paclitaxel; ECOG PS, Easte

FAQs

What biomarkers were measured in the J-TAIL-2 exploratory study?

The study evaluated approximately 560 cancer- or immune-related proteins in blood plasma. Measurements were performed using the Proximity Extension Assay at baseline, before the second atezolizumab dose, and at immune-related adverse event onset.

Which protein markers were associated with shorter progression-free survival?

IL-6, MUC-16, and KRT-19 were associated with shorter progression-free survival across multiple regimens.

How did protein findings relate to immune-related adverse events and treatment response?

Baseline immune stimulation proteins were linked to immune-related adverse events across regimens. Immune activation markers, including Granzyme A and B, were elevated in responders receiving atezolizumab plus CnP and atezolizumab plus bevacizumab-carboplatin-paclitaxel.

Sep 23, 2026

Uploaded by Ben