Journal Article

Anti-PD1 based precision induction therapy in unresectable stage III non-small cell lung cancer: a phase II umbrella clinical trial

Liu, Xiaogang, Jiang, Gening, Shen, Ziyun, Zhang, Peng, Wang, Jue, Xie, Dong, Yi, Chengxiang, Zhao, Deping, Duan, Liang, Song, Nan, Zhu, Yuming, Yu, Huansha, Dai, Jie, Hu, Shiqi, Wang, Suyu, Bian, Dongliang, Sun, Liangdong, He, Wenxin, Yan, Yilv, Zhang, Lele, Zhou, Yirui, Yang, Yong

2025

Overview

The efficacy and safety of induction-immunotherapy followed by surgery for unresectable Stage III non-small cell lung cancer (NSCLC) remain challenging. In this open-label, single-center, phase II clinical umbrella trial (ChiCTR2000035367), 100 unresectable Stage III NSCLC patients are enrolled. Patients with PD-L1 expression ≥ 50% but contraindications to anti-angiogenic therapy receive immuno-monotherapy. Patients with PD-L1 expression ≥ 1% and no contraindications to anti-angiogenic therapy receive immunotherapy plus anti-angiogenesis therapy. Patients with PD-L1 expression between 1% and 49%, contraindications to anti-angiogenic therapy, or negative/unknown PD-L1 expression receive chemoimmunotherapy. The primary endpoint is the major pathological response (MPR) rate. Among 47 surgically-treated patients, the MPR rate is 61.7% (95% confidence interval [CI]: 46.4%-75.5%), achieving the prespecified endpoint. For secondary endpoints, the objective response rate for all patients is 54.0% (95% CI: 43.7-64.0). The median event-free survival is 29.9 months (95% CI: 17.0-42.7). Most common adverse event is anemia (49.0%). Exploratory transcriptomic analyses reveal Bone Marrow Stromal Cell Antigen 1 (BST1) as a promising biomarker for response to chemoimmunotherapy. Generally, for unresectable stage III NSCLC patients, anti-PD1 based induction-therapy according to PD-L1 expression and contraindication to antiangiogenic therapy followed by surgery is a feasible option. Induction-immunotherapy before surgery has been suggested for patients with unresectable stage III non-small cell lung cancer (NSCLC). Here, the authors report a phase 2 umbrella clinical trial where patients with unresectable stage III NSCLC receive anti-PD1-based induction-therapy based on PD-L1 expression and contraindications to antiangiogenic therapy.

• Publisher: Nature Publishing Group UK,Nature Publishing Group,Nature Portfolio
• Subject: 45/23 / 49/91 / 631/67/1612/1350 / 692/308/2779/109/1941 / 692/308/53/2423 / Adult / Aged / Anemia / Angiogenesis / Angiogenesis Inhibitors - therapeutic use / Antiangiogenics / B7-H1 Antigen - antagonists & inhibitors / B7-H1 Antigen - genetics / B7-H1 Antigen - metabolism / Biomarkers / Bone marrow / Carcinoma, Non-Small-Cell Lung - drug therapy / Carcinoma, Non-Small-Cell Lung - genetics / Carcinoma, Non-Small-Cell Lung - pathology / Carcinoma, Non-Small-Cell Lung - therapy / Chemotherapy / Clinical trials / Contraindications / Female / Humanities and Social Sciences / Humans / Immune Checkpoint Inhibitors - therapeutic use / Immunotherapy / Immunotherapy - methods / Induction Chemotherapy - methods / Induction therapy / Lung cancer / Lung Neoplasms - drug therapy / Lung Neoplasms - genetics / Lung Neoplasms - pathology / Lung Neoplasms - therapy / Male / Middle Aged / multidisciplinary / Neoplasm Staging / Non-small cell lung carcinoma / Patients / PD-1 protein / PD-L1 protein / Precision Medicine - methods / Programmed Cell Death 1 Receptor - antagonists & inhibitors / Programmed Cell Death 1 Receptor - immunology / Science / Science (multidisciplinary) / Small cell lung carcinoma / Surgery / Therapy / Transcriptomics / Treatment Outcome