Immune Checkpoint Inhibitors (ICIs)

Currently, chemotherapy, targeted therapy, immunotherapy, and radiotherapy are the core treatment modalities for malignant tumors, with technologies advancing rapidly. Radiotherapy can induce massive tumor cell death in a short period and expose abundant tumor-specific antigens, turning the irradiated tumor into an endogenous tumor vaccine and even causing regression or disappearance of non-irradiated tumors (the abscopal effect) . Preclinical studies have shown that stereotactic body radiotherapy (SBRT) combined with PD-1/PD-L1 inhibitors can activate systemic immunity, sensitize tumor-specific T cells to enter the bloodstream, and enable their homing to distant tumors, thereby inhibiting the growth of non-irradiated tumors . However, conclusions from rigorous randomized controlled trials have limitations when applied to the complex and heterogeneous patient populations in real-world settings. Real-world research is increasingly valued globally to complement traditional clinical trial evidence. This project prospectively collects data from patients receiving immunotherapy combined with radiotherapy in real-world clinical practice, which is of great value for evaluating long-term efficacy, safety, and impact on quality of life, and can provide high-level evidence for optimizing clinical practice and informing healthcare decisions.

The population receiving immunotherapy is heterogeneous. Multiple factors, including combination treatment modalities, influence the immune response, and survival outcomes also vary among individuals receiving immunotherapy. The aim of this study is to develop and validate a clinical prediction model that can predict survival outcomes of immunotherapy for malignant tumors, and to assess the calibration and discrimination of this model in a prospective independent cohort.

Study Objectives The primary objective of Phase II is to evaluate the percentage of lesion resolution on high-resolution computed tomography (HRCT) as assessed by independent blinded reviewers. Secondary objectives include evaluating effects on pulmonary function, exercise capacity, dyspnea, quality of life, and oxygenation, as well as comprehensively assessing safety and tolerability. Phase I focuses on determining safety, dose-limiting toxicities (DLT), and recommended Phase II dose. Study Population The target population is patients with non-acute CIP aged 18-75 years with histologically confirmed malignancy. Key inclusion criteria include: At least one cycle of immune checkpoint inhibitor (ICI) therapy and development of Grade 3-4 CIP per NCCN Guidelines V1.2025 Standard glucocorticoid treatment for ≥4 weeks, with current dose \<20 mg/day prednisone equivalent or discontinued Persistent residual CIP lesions on HRCT without significant improvement in the past 4 weeks ECOG PS 0-1 and stable primary tumor for ≥6 months Effective contraception during the study and for 360 days after last dosing Key exclusion criteria include: Concomitant use of pirfenidone, nintedanib, or other antifibrotic agents Inability to perform pulmonary function tests or tolerate nebulization Unresolved interstitial lung disease from radiotherapy or targeted therapy Severe cardiac, hepatic, renal, or hematological dysfunction Organ transplantation, severe immunodeficiency, active epilepsy, or severe allergic status Other investigational drug use within 28 days Study Design and Sample Size Phase I: 9-18 subjects, open-label, dose-escalation design to evaluate DLT and safety Phase II: 40 subjects, randomized, double-blind, placebo-controlled design Study Endpoints Phase I Primary Endpoints Incidence of DLT Incidence of adverse events (AE) and serious adverse events (SAE) Phase II Primary Endpoint Percentage of HRCT lesion resolution at Weeks 4, 12, and 24, assessed by independent blinded reviewers Secondary Endpoints Pulmonary function: FVC%, TLC, RV, FRC, DLCO Functional and symptomatic measures: 6MWD, mMRC dyspnea score, SGRQ, LCQ Oxygenation: PaO₂, A-aDO₂, oxygenation index Exploratory Endpoints Dynamic changes in serum biomarkers: KL-6, cytokines (IL-1β, IL-6, IL-10), immune cell subsets (Tregs, Th1/Th17) Safety Assessments Monitoring of AEs/SAEs graded by CTCAE v5.0 and causality assessment Physical examination, vital signs, SpO₂, 12-lead ECG Laboratory tests: CBC, biochemistry, coagulation, urinalysis, CRP, ESR Study Termination Rules Overall Study Termination Successful completion after all 40 subjects finish 24-week follow-up and database lock Occurrence of unexpected serious or unacceptable safety risks Demonstration of overwhelming efficacy or futility Sponsor termination due to slow enrollment, funding, or major protocol deviations Regulatory or ethics committee requirements Individual Subject Discontinuation Development of DLT or severe hypersensitivity Rapid CIP progression (e.g., \>50% radiological worsening) Tumor progression or clinical deterioration Withdrawal of informed consent Poor compliance unresponsive to intervention Loss to follow-up or death Investigator judgment of inappropriateness for continued participation Study Timeline Preparation and initiation: January 2026 - May 2026 Phase I/II enrollment: June 2026 - May 2027 Treatment and follow-up (overlapping with enrollment): through June 2028 Database lock and statistical analysis: July 2028 - August 2028 Study closeout: August 2028 - December 2028

The purpose of this observational study is to explore the incidence, risk factors, and relationship with therapeutic outcomes of VTE (venous thromboembolism) and ATE (arterial thromboembolism) associated with immune checkpoint inhibitors (ICIs) therapy. The primary questions it aims to address are: 1. What is the real-world incidence of VTE/ATE in lung cancer patients receiving immune checkpoint inhibitors? 2. What are the risk factors and biomarkers for VTE/ATE in lung cancer patients receiving immune checkpoint inhibitors? 3. What is the impact of VTE/ATE on the prognosis of lung cancer patients receiving immune checkpoint inhibitors? Researchers will compare the characteristics and biomarkers of patients with and without ICI-associated VTE/ATE to identify novel specific biomarkers for thrombotic events. Furthermore, they will construct a risk assessment model for thrombotic events to provide guidance for precision prevention and treatment in clinical practice.

The CR1STAL-Adaptive study is a randomized, open-label, phase II multicenter interventional trial designed to evaluate the safety and efficacy of Ivonescimab (PD-1/VEGF bispecific antibody) combined with docetaxel versus standard treatment in patients with advanced NSCLC who have achieved long-term benefit from first-line immune checkpoint inhibitors (ICIs), but are ctDNA-MRD positive. Building upon insights from previous CR1STAL study (NCT05198154), the CR1STAL-Adaptive study supports the development of precision-guided, adaptive treatment strategies to delay progression and improve outcomes in NSCLC patients with a long-term response to immunotherapy. It represents a step forward in integrating dynamic molecular monitoring with individualized intervention strategies in the era of immunotherapy.

The goal of this observational study is to learn if emotional distress affects how well liver cancer treatment works in people receiving immunotherapy. Emotional distress means feeling anxious or depressed. The study aims to answer whether having emotional distress before treatment or changes in emotional distress during treatment affect how well immunotherapy works to treat liver cancer. Researchers will compare participants with and without emotional distress to examine differences in how long the cancer stays under control, treatment response, and overall survival time. Study participants will complete mood and quality of life questionnaires, meet with mental health specialists for emotional assessments, undergo regular blood tests to measure stress hormones, have routine medical check-ups and scans to monitor their cancer status, and be followed for up to 3 years. The study includes three groups of people with liver cancer: those starting immunotherapy for cancer that cannot be removed by surgery, those receiving immunotherapy after surgery, and those receiving immunotherapy before surgery. To be eligible for participation, individuals must be 18 years or older, diagnosed with liver cancer, about to start immunotherapy treatment, and able to complete mood questionnaires.

This is a single-center, retrospective, observational, real-world study. We collected general and clinical data of patients with advanced gastric cancer who were admitted to the First Affiliated Hospital of Zhengzhou University from January 2018 to July 2024.

The aim of this clinical trial is to evaluate the efficacy and safety of consolidation therapy with a neoantigen-loaded dendritic cell vaccine (NeoDC-Vac) following radical chemoradiotherapy or chemoradiation-immunotherapy in patients with locally advanced, unresectable ESCC. The primary endpoint of the study is the OS rate. Secondary endpoints include OS, PFS, adverse events, CR rate, and quality of life (QoL) of patients. Exploratory endpoints involve the assessment of biomarkers such as TMB, PD-L1, and ctDNA. The key questions this study aims to answer are: -Can the combination of (ICIs and NeoDC-Vac as maintenance therapy improve OS and QoL in patients with locally advanced, unresectable ESCC following radical treatment? Can this novel approach provide an effective treatment option for these patients? Participant Procedures: 1. Endoscopic examination at West China Hospital. Baseline fresh tumor tissue collection for NGS in neoantigen vaccine group. 2. Screening assessments, informed consent, and random assignment to experimental or control group. Experimental Group\*\*: Neoantigen-loaded vaccine + standard ICIs as maintenance therapy. Control Group\*\*: Standard ICIs as maintenance. One cycle per month for one year. 3. Tumor tissue NGS, ctDNA analysis, TIME evaluation, T cell response profiling. All costs covered by research funding. 4. After completing the full treatment regimen, participants will be monitored with regular follow-up visits by healthcare professionals to assess ongoing health outcomes and safety.