The Eastern Cooperative Oncology Group (ECOG) and Performance Status (PS) score was 2. treatment, immunotherapy, poor general condition, immune checkpoint inhibitor, chemotherapy, progression, driver gene-negative Introduction Lung cancer is the leading cause of cancer-related death in the world. Non-small cell lung cancer (NSCLC) accounts for approximately 85% of all lung cancers and is usually diagnosed at an advanced stage.1 The prognosis of these patients remains poor. Standard treatment for NSCLC patients with metastatic disease is platinum doublet therapy with gemcitabine, vinorelbine, or taxanes, and with pemetrexed in patients with the nonsquamous histologic type.2 For patients with driver variants, targeted therapies, such as epidermal growth factor receptor tyrosine kinase inhibitors (TKIs) and anaplastic lymphoma kinase (ALK) TKIs, are also recommended strategies.2 Recently, immunotherapy has become a highly promising therapeutic approach for lung cancer. Immune checkpoint inhibitors (ICIs), such as programmed cell death 1 (PD-1) and PD ligand 1 (PD-L1) monoclonal antibodies, have tumor-suppressing effects, facilitating a positive immune response to kill tumor cells.3 The use of these drugs significantly improves survival in patients with advanced NSCLC, especially in those without driver variants.4 Two PD-1 monoclonal antibodies, pembrolizumab and nivolumab, were approved for second-line chemotherapy in NSCLC by the United States Food and Drug Administration (USFDA) in 2015; atezolizumab, a PD-L1 monoclonal antibody, was approved for the same indication in 20165. Toripalimab, a recombinant, humanized PD1 monoclonal antibody, has been approved in China to treat metastatic melanoma patients who do not respond to systemic therapy.6 There are also ongoing clinical trials evaluating toripalimab in various types of cancers, including NSCLC. Here, we report a patient with Upamostat NSCLC who progressed after several chemotherapy cycles and who survived after receiving toripalimab. Case report A 61-year-old man with a 60 pack-year smoking Upamostat history visited our hospital in June 2017 with a chief complaint of right hip pain for 5 months. Bone scintigraphy showed multiple imaging abnormalities, indicating possible metastasis. Positron emission tomography-computed tomography (PET-CT) revealed a hypermetabolic mass (5.3??4.0?cm) in the anterior segment of the upper lobe of the right lung invading the right hilar region Upamostat and mediastinum. Signs of metastasis were as follows: several nodules were present in both lungs and the right pleura; multiple hypermetabolic lymph nodes were seen in the left neck, bilateral clavicular region, mediastinum, bilateral hilar region, and right cardiac diaphragmatic angle; hypermetabolic nodules were seen in bilateral adrenal glands; and bone destruction with metabolic activity was identified. The patient underwent bronchoscopy and was diagnosed with adenocarcinoma through pathology. Molecular analysis showed no driver gene mutations. We diagnosed advanced lung adenocarcinoma on histopathology (Figure 1) according to the 8th edition of the American Joint Committee on Cancer (AJCC) tumor-node-metastasis (TNM) staging system (stage: T4N3M1c, IVB) (Figure 2a). Between 15 July 2017 and 28 November 2017, we administered six cycles of chemotherapy combined with targeted therapy consisting of pemetrexed, carboplatin, and bevacizumab (pemetrexed: 500?mg/m2 on day 1, FLJ12894 carboplatin (area under the curve (AUC)?=?5) on day 1, and bevacizumab 7.5?mg/kg on day 1; repeated every 21 days), after obtaining patient consent for treatment. We administered zoledronic acid concurrently, for bone metastasis. After four cycles, enhanced chest CT revealed partial response (PR) (Figure 2b). According to the patients wishes, he received only one cycle of pemetrexed and bevacizumab maintenance therapy, on 23 January 2018. Periodic surveillance scans demonstrated stable disease until November 2018. Enhanced chest CT scan at that time showed enlargement of the primary lesion (from 30??23?mm to 48??41?mm) and an increase in the number of subpleural nodules (Figure 2c). In April 2019, the patient underwent enhanced brain magnetic resonance imaging, which revealed a new metastasis in the cortex of the frontal lobe. The progression-free survival with first-line chemotherapy (PFS1) was 16 months. Open in a separate window Figure 1. The Upamostat patients pathology findings (hematoxylin and eosin, Upamostat 109). Open in a separate window Figure 2. Computed tomography (CT) images (a) Baseline images. (b) Enhanced CT images after four cycles of first-line pemetrexed, carboplatin, and bevacizumab treatment. (c) Enhanced CT images indicating a relapse of the primary lesion. The patient received two cycles of pemetrexed and carboplatin combined with bevacizumab rechallenge therapy, but enhanced CT performed after two cycles showed progressive disease (PD) (Figure 3aCc) with newly identified bone metastasis. He then received two cycles of chemotherapy with Abraxane (Celgene Corp., Summit, NJ, USA) which also failed (Figure 4a). We changed the drug to anlotinib targeted therapy for two cycles, which also resulted in PD,.