Obstructive Sleep Apnea Influences Efficacy of PD-1-Based Immunotherapy Against Non-Small Cell Lung Cancer

Recruiting

• Conditions: Non-small Cell Lung Cancer; Obstructive Sleep Apnea

• Registration Number: NCT04743752
• Lead Sponsor: Peking University First Hospital

Brief Summary

This prospective, observational cohort study aims to explore the influence of obstructive sleep apnea(OSA) on the efficacy of PD-1-based immunotherapy in patients with non-small cell lung cancer(NSCLC). Patients who had no prior treatment for advanced NSCLC and are intended to receive PD-1/PD-L1 antibody will be recruited. According to sleep monitor results, participants will be divided into Group NSCLC and Group OSA+NSCLC. Primary outcome is the objective remission rate(ORR).

Detailed Description

This is a single-center, prospective, observational cohort study. Patients who had no prior treatment for advanced NSCLC and are intended to receive PD-1/PD-L1 antibody will be recruited and followed for 4 years. According to the baseline sleep monitor results, participants will be divided into Group NSCLC(AHI\<15), and Group OSA+NSCLC(AHI≥15), and then explore the influence of obstructive sleep apnea on the efficacy of PD-1-based immunotherapy. The baseline level of white blood cell count (WBC); absolute neutrophil count (ANC); absolute lymphocyte count (ALC); ANC to ALC (ANC:ALC) ratio; interleukin 6 (IL-6); C-reactive Protein (CRP) in peripheral blood, lymphocytes classification and count by flow cytometry, and gut microbiome analysis by quantitative metagenomics will also be measured to further search for the possible mechanisms. Primary outcome is the objective remission rate (ORR), secondary outcomes include overall survival (OS) and progression free survival (PFS).

The study protocol has been approved by the Peking University First Hospital Institutional Review Board (IRB). Any protocol modifications will be submitted for the IRB review and approval.

Study Timeline

• Study First Submitted: 2021-01-30
• Study First Submitted QC: 2021-02-04
• Study First Posted: 2021-02-08
• Study Start: 2021-02-23
• Status Verified: 2022-04
• Last Update Submitted: 2022-04-24
• Last Update Posted: 2022-04-26
• Primary Completion: 2025-12-31
• Study Completion: 2025-12-31

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 200

Inclusion Criteria

1. Histologically or cytologically confirmed, advanced NSCLC
2. Participants with no prior treatment for advanced NSCLC
3. Measurable disease as defined by RECIST v1.1
4. Eligible to receive first-line treatment including PD-1 antibody
5. Adequate hematologic and end organ function

Exclusion Criteria

1. Severe infection within 4 weeks prior to recruitment.
2. Significant organ dysfunction or other serious diseases.
3. Previous or current OSA related treatment, including oral appliance, surgery, mechanical ventilation therapy.
4. Illness or condition that interferes with the participant's capacity to understand, follow and/or comply with study procedures.

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Objective response rate(ORR)	From date of randomization until the date of first documented progression, assessed up to 48 months	ORR, the percentage of complete response (CR) or partial response (PR) according to RECIST 1.1 standard definition.CR: disappearance of all target and non-target lesions and (if applicable) normalization of tumor marker level; or reduction in short axis of any pathological lymph nodes (whether target or non-target) to less than (\<) 10 mm. PR: at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters; or persistence of one or more non-target lesion(s) and/or (if applicable) maintenance of tumor marker level above the normal limits.

Secondary Outcome Measures

Name	Time	Method
Factors associated with ORR in NSCLC patients	From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 48 months	Cox regression analysis will be used to identify predictors of ORR.
Overall survival (OS)	From date of randomization until the date of death from any cause, assessed up to 48 months	OS was defined as the time from the date of enrollment to the date of death due to any cause.
Compared the baseline gut microbiome between Group NSCLC and Group OSA+NSCLC.	From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 48 months	Record baseline gut microbiome by metagenomic shotgun sequencing, then compare between Group NSCLC and Group OSA+NSCLC.
The association between OSA and the diversity of gut microbiome.	From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 48 months	The Spearman correlation test will be used to identify the association between sleep monitor results and the diversity of gut microbiome, including AHI, ODI, lowest SpO2, SpO2\<90%, OAI, CAI, the longest apnea duration.
Factors associated with OS and PFS in NSCLC patients	From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 48 months	Univariate and multivariate Cox proportional hazards models will be used to identify predictors of PFS and OS.
The association between OSA and baseline inflammatory biomarkers, peripheral lymphocytes classification and count.	From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 48 months	The Spearman correlation test will be used to identify the association between sleep monitor results and the baseline inflammatory biomarkers, peripheral lymphocytes classification and count, including AHI, ODI, lowest SpO2, SpO2\<90%, OAI, CAI, the longest apnea duration
Progression-Free Survival (PFS)	From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 48 months	PFS was defined as the time from recruitment to the first occurrence of progressive disease(PD) or death due to any cause. PD: at least a 20 percent increase in the sum of diameters of target lesions, taking as reference the smallest sum on study, including baseline, and an absolute increase of at least 5 mm; appearance of one or more new target or non-target lesions; or unequivocal progression of existing non-target lesions.
Compared the baseline level of inflammatory biomarkers between Group NSCLC and Group OSA+NSCLC.	From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 48 months	Record baseline interleukin 6 (IL-6) and C-reactive Protein (CRP) in peripheral blood, then compare between Group NSCLC and Group OSA+NSCLC.
Compared the baseline sleep monitor results between Group NSCLC and Group OSA+NSCLC.	From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 48 months	Record baseline AHI, oxygen desaturation index (ODI), lowest saturation by pulse oximetry (SpO2)\<90%, obstructive apnea index (OAI), central apnea index(CAI), the longest apnea duration, then compare between Group NSCLC and Group OSA+NSCLC.
Compared the baseline level of lymphocytes classification and count between Group NSCLC and Group OSA+NSCLC.	From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 48 months	Record baseline lymphocytes classification and count in peripheral blood, then compare between Group NSCLC and Group OSA+NSCLC.

Trial Locations

Locations (1)

Peking University First Hospital; 🇨🇳 Beijing, Beijing, China