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

Affiliated Hospital of Nantong University

Status: Completed

Conditions: Lung Cancer

Treatments: Drug: β-adrenergic receptor blocker; Drug: Camrelizumab

Study type: Observational

Funder types: Other

Identifiers

NCT05387512

2022-K002-01

Details and patient eligibility

About

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.

Full 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.

Enrollment: 59 patients

Sex: All

Ages: 18 to 100 years old

Volunteers: No Healthy Volunteers

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.

Trial design

59 participants in 2 patient groups

Camrelizumab treatment group

Description:

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.

Treatment:

Drug: Camrelizumab

Camrelizumab + β-blocker Combination treatment group

Description:

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.

Treatment:

Drug: Camrelizumab

Drug: β-adrenergic receptor blocker