Effect of Time-of-Day (ToD) for Immunochemotherapy on PFS in NSCLC

NCT05549037 | Recruiting Phase 3

• 1 other identifier: INJECTION
• Study Type: interventional
• Target: 210
• Locations: 1 country
• Sites: 1

Brief Summary

This study aims to explore time-of-day of administration of immunochemotherapy on the efficacy for treatment naive advanced non-small cell lung cancer.

Conditions

Non-small Cell Lung Cancer

Keywords

Immunochemotherapy; Time of day; Non-small Cell Lung Cancer

Outcome Measures

Primary Outcomes (1)

• Progression-free survival (PFS)

  To assess progression-free survival of patients treated by immunochemotherapy according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 by investigator, define as first dose to first documented disease progression assessed by investigator or death due to any cause.

  Time from first subject dose to study completion, or up to 36 month.

Secondary Outcomes (3)

• Objective Response Rate (ORR)

  Time from first dose to last dose, or up to 24 month.

• Overall survival (OS)

  Time from first subject dose to study completion, or up to 24 month.

• Duration of Response (DoR)

  Time from first subject dose to study completion, or up to 24 month.

Study Arms (2)

Arm A: Morning group

EXPERIMENTAL

All the patients in this arm will be treated with immunochemotherapy before 15:00.

Drug: Pembrolizumab, Sintilimab

Arm B: Afternoon group

EXPERIMENTAL

All the patients in this arm will be treated with immunochemotherapy after 15:00.

Drug: Pembrolizumab, Sintilimab

Interventions

Pembrolizumab, Sintilimab DRUG

One for morning group, the patients in this group were treated with immunochemotherapy before 15:00. One for afternoon group, the patients in this group were treated with immunochemotherapy after 15:00.

Also known as: time-of-day of administration of immunochemotherapy

Arm A: Morning group; Arm B: Afternoon group

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Understand the requirements and contents of the clinical trial, and provide a signed and dated informed consent form.
• Age ≥ 18 years.
• Histopathology or cytology confirmed and recorded local progression or metastatic non-small cell lung cancer without systemic treatment.
• EGFR, ALK and ROS1 mutations negative confirmed by an accredited local laboratory.
• ECOG 0-1.
• Predicted survival ≥ 12 weeks.
• Adequate bone marrow hematopoiesis and organ function
• Presence of measurable lesions according to RECIST 1.1.
• Subjects with stable brain metastases may be included in the study.

You may not qualify if:

• Prior systemic therapy for locally advanced or metastatic disease.
• Subjects who have received any of the following treatments must be excluded:
• Ant Treatment with chemotherapy or molecules such as EGFR, VEGFR antibodies within 4 weeks prior to the first dose of study drug.
• Have received radiation within 14 days prior to the first dose or have not recovered from radiation-related toxicity. Chest and extra-brain palliative radiotherapy, stereotactic radiosurgery, and stereotactic body radiotherapy may be performed 7 days prior to the first dose.
• Presence of spinal cord compression or meningeal metastasis.
• History of other malignant tumors within 2 years.
• Adverse events (except alopecia of any degree) of CTCAE \> grade 1 due to prior treatment (e.g., adjuvant chemotherapy, radiotherapy, etc.) prior to the first dose.
• History of stroke or intracranial hemorrhage within 6 months prior to the first dose.
• The presence of any severe or poorly controlled systemic disease, including poorly controlled hypertension and active bleeding in the judgment of the investigator.
• Subjects with persistent or active infection, including but not limited to hepatitis B (HBV), hepatitis C (HCV), human immunodeficiency virus (HIV) and COVID-19 infection.
• Heart-related diseases or abnormalities
• Past history of interstitial lung disease, drug-induced interstitial lung disease, radiation pneumonitis requiring steroid therapy or interstitial lung disease with active clinical symptoms, immune pneumonia caused by immunotherapy.
• Refractory nausea and vomiting, chronic gastrointestinal disease, difficulty swallowing drugs, or inability to adequately absorb sunvozertinib or anlotinib due to previous bowel resection.
• Live vaccine was given 2 weeks before the first medication.
• Women who are breastfeeding or pregnant.

Sponsors & Collaborators

• Hunan Province Tumor Hospital: lead

Study Sites (1)

Hunan Cancer Hospital

Changsha, Hunan, 410013, China

RECRUITING

Related Publications (1)

• Huang Z, Zeng L, Ruan Z, Zeng Q, Yan H, Jiang W, Xiong Y, Zhou C, Yang H, Liu L, Dai J, Zou N, Xu S, Wang Y, Wang Z, Deng J, Chen X, Wang J, Xiang H, Li X, Duchemann B, Chen G, Xia Y, Mok T, Scheiermann C, Levi F, Yang N, Zhang Y. Time-of-day immunochemotherapy in nonsmall cell lung cancer: a randomized phase 3 trial. Nat Med. 2026 Feb 2. doi: 10.1038/s41591-025-04181-w. Online ahead of print.

  PMID: 41629425 DERIVED

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Interventions

pembrolizumab; sintilimab

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Study Officials

• Yongchang Zhang, MD

  Hunan Cancer Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Yongchang C Zhang, MD

CONTACT

+8613873123436; zhangyongchang@csu.edu.cn

Yongchang Zhang, MD

CONTACT

+8613873123436; zhangyongchang@csu.edu.cn

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Director, Head of Medical Oncology, Principal Investigator, Clinical Professor

Model Details: One for morning group, the patients in this group were treated with chemotherapy plus pembrolizumab or sintilimab before 15:00. One for afternoon group, the patients in this group were treated with chemotherapy plus pembrolizumab or sintilimab after 15:00.

Study Record Dates

• First Submitted: September 17, 2022
• First Posted: September 22, 2022
• Study Start: September 23, 2022
• Primary Completion: December 2, 2024
• Study Completion: December 31, 2025
• Last Updated: February 19, 2025

Record last verified: 2025-02

Locations

CN (1)