Consolidation Radiotherapy vs. Observation in Oligoresidual Advanced Non-Small Cell Lung Cancer After Chemo-Immunotherapy

NCT07014202 | Recruiting Phase 2

• 1 other identifier: NCC4839
• Study Type: interventional
• Target: 224
• Locations: 1 country
• Sites: 1

Brief Summary

This clinical study investigates whether adding local radiation therapy (radiotherapy) to standard maintenance therapy benefits patients with advanced non-small cell lung cancer (NSCLC) who have a limited number of residual tumors after initial treatment. The primary objective is to determine if adding targeted radiation therapy to residual lesions prolongs progression-free survival in NSCLC patients with "oligo-residual lesions" (5 or fewer tumors in no more than 3 organs) following first-line chemoimmunotherapy. Researchers hypothesize that combination therapy will slow cancer progression more effectively than maintenance therapy alone. Eligible participants include adults (18+) with advanced NSCLC who have completed 4-6 cycles of first-line chemoimmunotherapy, show limited residual disease on Positron Emission Tomography-Computed Tomography (PET-CT), and lack specific genetic mutations (Epidermal Growth Factor Receptor \[EGFR\], Anaplastic Lymphoma Kinase \[ALK\], etc.). Patients will be randomized into two groups: Experimental: Continuation of maintenance therapy (immunotherapy alone or with chemotherapy) plus local radiotherapy to all residual tumors Control: Continuation of maintenance therapy only The study aims to answer: Primary: Does adding radiotherapy slow cancer progression more effectively? Secondary: Does it improve overall survival, control residual disease, and what are its effects on safety and quality of life? Participants will: Be randomly assigned to a treatment group Receive their designated treatment Undergo regular check-ups and imaging scans Complete quality of life questionnaires Potentially provide blood samples for research This research will help determine optimal treatment approaches for this specific patient population to improve outcomes and quality of life.

Conditions

Non-Small Cell Lung Cancer

Outcome Measures

Primary Outcomes (1)

• Progression-Free Survival (PFS)

  Time from randomization (with or without radiotherapy) to first occurrence of objective disease progression (Response Evaluation Criteria in Solid Tumors \[RECIST\] 1.1) or death from any cause (if occurring before disease progression).

  The estimated median PFS time from entry into maintenance therapy to recurrence in the control group is 6 months. The experimental group is expected to extend median PFS time from 6 months to 8.7 months.

Study Arms (2)

Maintenance therapy combined with radiotherapy group

EXPERIMENTAL

Radiotherapy Protocol: Target all residual primary lesions and all metastatic sites (pulmonary, hepatic, osseous, lymphadenopathy). Fractionation determined by treating physician after multidisciplinary consultation. For lesions near critical organs, appropriate fractionation/total doses selected per clinical situation. Maintenance Therapy Protocol: Based on latest National Comprehensive Cancer Network (NCCN)/Chinese Society of Clinical Oncology(CSCO) guidelines for stage IV non-small cell lung cancer (NSCLC). For lung adenocarcinoma: Following 4-6 cycles of first-line therapy (pemetrexed+platinum+immunotherapy) Maintenance: Pemetrexed (500mg/m²) + pembrolizumab 200mg IV q3w. Duration: Maximum 24 months (until week 96, disease progression, unacceptable toxicity, consent withdrawal, or other termination criteria). All trial patients receive immunotherapy maintenance

Combination Product: Immunotherapy (with or without chemotherapy) maintenance therapy combined with radiotherapy

Maintenance therapy

ACTIVE COMPARATOR

Based on latest NCCN/CSCO guidelines for stage IV NSCLC. For lung adenocarcinoma: Following 4-6 cycles of first-line therapy (pemetrexed+platinum+immunotherapy) Maintenance: Pemetrexed (500mg/m²) + pembrolizumab 200mg IV q3w. Duration: Maximum 24 months (until week 96, disease progression, unacceptable toxicity, consent withdrawal, or other termination criteria). All trial patients receive immunotherapy maintenance

Drug: Immunotherapy (with or without chemotherapy) maintenance therapy

Interventions

Immunotherapy (with or without chemotherapy) maintenance therapy combined with radiotherapy COMBINATION_PRODUCT

Immunotherapy (with or without chemotherapy) maintenance therapy combined with radiotherapy in patients with advanced NSCLC who have not progressed after 4-6 cycles of first-line platinum-containing chemotherapy combined with immunotherapy and who have an oligo-residual status confirmed by PETCT.

Maintenance therapy combined with radiotherapy group

Immunotherapy (with or without chemotherapy) maintenance therapy DRUG

Immunotherapy (with or without chemotherapy) maintenance therapy in patients with advanced NSCLC who have not progressed after 4-6 cycles of first-line platinum-containing chemotherapy combined with immunotherapy and who have an oligo-residual status confirmed by PETCT.

Maintenance therapy

Eligibility Criteria

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

You may qualify if:

• Voluntary signed written informed consent and compliance with protocol requirements;
• Age ≥ 18 years;
• Expected survival time ≥ 3 months;
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1;
• Histologically or cytologically confirmed advanced non-small cell lung cancer;
• After receiving 4-6 cycles of first-line platinum-based chemotherapy combined with immunotherapy, PET-CT evaluation shows no disease progression, with no more than 5 lesions not meeting criteria for complete metabolic response, involving no more than 3 organs;
• All residual lesions can safely receive radiation therapy as assessed by radiation oncologists;
• Patient can tolerate the radiotherapy process, such as maintaining fixed position;
• At least one measurable lesion among the oligoresidual lesions according to RECIST v1.1;

You may not qualify if:

• Laboratory values at screening must meet the following criteria: a) Neutrophils ≥ 1.5×10\^9/L b) Platelets ≥ 100×10\^9/L c) Hemoglobin ≥ 90g/L (no blood transfusion within 14 days) d) Serum Cr ≤ 1×ULN, endogenous creatinine clearance \> 50ml/min (Cockcroft-Gault formula) e) AST ≤ 2.5×ULN; ALT ≤ 2.5×ULN; if liver metastases present, ALT and AST ≤ 5×ULN f) Total bilirubin ≤ 1.5×ULN (except for Gilbert's syndrome subjects, where total bilirubin must be \< 51.3μmol/L) g) Thyroid Stimulating Hormone (TSH), Free Triiodothyronine (FT3), Free Thyroxine (FT4) all within ±10% of normal range.
• Archived tumor tissue, pre-treatment tumor biopsy, or histological examination showing evidence of previous small cell or mixed small cell/non-small cell histology;
• Previous tissue samples or peripheral blood genetic sequencing reports indicating EGFR sensitizing mutations, ALK fusion, or other gene variations that should receive standard first-line targeted therapy; squamous cell carcinoma without genetic testing is presumed negative;
• Symptomatic brain metastases;
• Leptomeningeal metastases;
• Active, known, or suspected autoimmune disease (excluding vitiligo, type I diabetes, residual hypothyroidism due to autoimmune thyroiditis requiring only hormone replacement therapy, or conditions not expected to recur in the absence of external triggers);
• Active tuberculosis (TB) infection as determined by chest X-ray, sputum examination, and clinical examination. Patients with a history of active pulmonary TB infection within the previous year, even if treated, will be excluded. Patients with a history of active pulmonary TB infection more than 1 year ago will also be excluded unless effective previous anti-TB treatment can be documented;
• Comorbidities requiring immunosuppressive medication, or requiring systemic or local use of corticosteroids at immunosuppressive doses;
• Pregnancy or breastfeeding;
• Interstitial lung disease with symptomatic manifestations, or that may interfere with the detection or management of suspected drug-related pulmonary toxicity;
• Positive for human immunodeficiency virus antibody (HIVAb), active hepatitis B virus infection (HBsAg positive and HBV-DNA \> 10\^3 copies/ml), or hepatitis C virus infection (HCV antibody positive and HCV-RNA \> lower limit of detection at the research center);
• History of severe neurological or psychiatric disorders, including but not limited to: dementia, depression, seizures, bipolar disorder, etc.;
• Receipt of other investigational drugs or treatments within 4 weeks prior to study randomization;
• Use of any Chinese herbal medicines with anti-tumor activity within 2 weeks prior to study drug administration;
• History of other malignancies (excluding non-melanoma skin cancer and the following in situ cancers: bladder, gastric, colon, endometrial, cervical/dysplasia, melanoma, or breast), unless complete remission was achieved at least 2 years prior to study enrollment and no additional therapy is required or anticipated during the study period;

Sponsors & Collaborators

• Cancer Institute and Hospital, Chinese Academy of Medical Sciences: lead

Study Sites (1)

National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College

Beijing, Beijing Municipality, 100021, China

RECRUITING

Related Publications (18)

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MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Interventions

Immunotherapy; Radiotherapy; Maintenance

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Immunomodulation; Biological Therapy; Therapeutics; Health Care Facilities Workforce and Services

Study Officials

• Zhijie Wang

  Cancer Institute and Hospital, Chinese Academy of Medical Sciences

  STUDY DIRECTOR

Central Study Contacts

Zhijie Wang, MD

CONTACT

+8613466323860; jie_969@163.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: May 26, 2025
• First Posted: June 10, 2025
• Study Start: June 11, 2025
• Primary Completion (Estimated): September 1, 2027
• Study Completion (Estimated): September 1, 2027
• Last Updated: July 30, 2025

Record last verified: 2025-05

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)