A Real World Study of β2-Adrenergic Blocker Plus PD-1 Inhibitor in Non-Small Cell Lung Cancer

NCT ID: NCT05387512

Last Updated: 2026-01-06

Basic Information

• Recruitment Status: COMPLETED
• Total Enrollment: 59 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2022-01-12
• Study Completion Date: 2025-11-30

Brief Summary

This study aims to explore an optimized treatment regimen of camrelizumab for Chinese patients with non-squamous non-small cell lung cancer. We will evaluate the efficacy, safety, and cost-effectiveness of camrelizumab monotherapy versus camrelizumab combined with a beta-adrenergic receptor blocker. Based on real-world data, a Markov model will be established to analyze the incremental cost-effectiveness of the combination therapy compared to monotherapy. Deterministic sensitivity analysis and probabilistic sensitivity analysis will be performed.

Detailed Description

1. Evaluate the feasibility, safety, and preliminary efficacy of adding a β-adrenergic receptor blocker to standard anti-PD-1 immunotherapy (camrelizumab). Studies suggest that sympathetic nervous system signaling, mediated through β-adrenergic receptors on T cells, may contribute to T cell dysfunction and resistance to immune checkpoint inhibitors. Our aim is to pharmacologically inhibit this pathway to assess whether the functional capacity of tumor-infiltrating T cells can be modulated, thereby potentially restoring or enhancing sensitivity to camrelizumab. We will systematically monitor patient outcomes, including tumor response and progression-free survival, and compare them against benchmarks.

2. Concurrently, this study incorporates a comprehensive pharmacoeconomic analysis. The goal is to determine the cost-effectiveness of the combination strategy (camrelizumab plus β-blocker) compared to camrelizumab monotherapy within the Chinese healthcare context. This evaluation will be conducted using a decision-analytic Markov model, which simulates the long-term clinical trajectory and associated costs of patients under each treatment strategy. The model will be populated with efficacy and safety data generated from this study, supplemented by real-world data on resource utilization and costs. To assess the robustness of the economic conclusions, deterministic sensitivity analysis (examining the impact of varying key parameters) and probabilistic sensitivity analysis (incorporating uncertainty across all parameters) will be performed. This analysis aims to provide evidence regarding the value of the combination strategy to inform clinical practice and healthcare resource allocation decisions.

Conditions

Lung Cancer

Study Design

• Observational Model Type: CASE_CONTROL
• Study Time Perspective: RETROSPECTIVE

Study Groups

Camrelizumab + β-blocker Combination treatment group

Patients receive camrelizumab in combination with a β2-adrenergic receptor blocker (e.g., a selective agent such as ICI-118551 used in preclinical models, or a clinically available alternative like propranolol). The specific β-blocker, dosing, and schedule will be defined in the study protocol. This arm directly tests the translational hypothesis derived from the preclinical finding that β-blockade reverses T cell exhaustion and restores sensitivity to anti-PD-1 therapy.

β-adrenergic receptor blocker

Intervention Type: DRUG

A β-blocker (specifically targeting the β2-adrenergic receptor, such as the selective antagonist ICI-118551 used in preclinical models, or a clinically available agent like propranolol) will be administered in combination with Camrelizumab. The specific agent, dose, route (e.g., oral), and schedule will be defined in the study protocol.

Camrelizumab

Intervention Type: DRUG

Camrelizumab is a humanized anti-PD-1 monoclonal antibody. The intervention will be administered as an intravenous infusion at a dose of 200 mg every 3 weeks, in accordance with the approved product label or the study protocol.

Camrelizumab treatment group

Patients receive camrelizumab (an anti-PD-1 antibody) alone. Reference regimen of Camrelizumab 200mg/3 weeks will follow the approved product label or study protocol. This arm corresponds to the "ICB therapy" group in the foundational preclinical study.

Camrelizumab

Intervention Type: DRUG

Camrelizumab is a humanized anti-PD-1 monoclonal antibody. The intervention will be administered as an intravenous infusion at a dose of 200 mg every 3 weeks, in accordance with the approved product label or the study protocol.

Interventions

β-adrenergic receptor blocker

A β-blocker (specifically targeting the β2-adrenergic receptor, such as the selective antagonist ICI-118551 used in preclinical models, or a clinically available agent like propranolol) will be administered in combination with Camrelizumab. The specific agent, dose, route (e.g., oral), and schedule will be defined in the study protocol.

Intervention Type: DRUG

Camrelizumab

Camrelizumab is a humanized anti-PD-1 monoclonal antibody. The intervention will be administered as an intravenous infusion at a dose of 200 mg every 3 weeks, in accordance with the approved product label or the study protocol.

Intervention Type: DRUG

Other Intervention Names

SHR-1210

Eligibility Criteria

Inclusion Criteria

(1)Histologically confirmed advanced (stage IIIB/IV) NSCLC; (2) Planned to receive first-line anti-PD-1/L1 monotherapy and deemed suitable for such treatment; (3) Older than 18 years of age; (4) ECOG (Eastern Oncology Collaboration group) score 0-1; (5) Ecg and liver and kidney function are normal; (6) No second primary tumor disease or serious complications.

Exclusion Criteria

(1) Known hypersensitivity to camrelizumab or any of its excipients, or to any component of the planned β-blocker; (2) Clear contraindications to the use of a β-adrenergic receptor blocker; (3)Active infection requiring systemic therapy;(4)Any other concurrent severe illness or clinical condition that, in the investigator's judgment, would interfere with the completion or interpretation of the study protocol or increase patient risk.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 100 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

The Affiliated Tumor Hospital of Nantong University, Nantong, Jiangsu Province, China

OTHER

Sponsor Role: collaborator

Affiliated Hospital of Nantong University

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Zhiyuan Tang, Doctor

Role: STUDY_DIRECTOR

Affilication Hospital of Nantong University

Locations

Department of Pharmacy, Affiliated Hospital of Nantong University

Nantong, Jiangsu, China

Countries

China

Other Identifiers

2022-K002-01

Identifier Type: -

Identifier Source: org_study_id