Adding targeted radiation to remaining lung tumors after chemo‑immunotherapy

Comparing Consolidation Radiotherapy Versus No Radiotherapy for Oligoresidual Disease After First-line Chemotherapy Plus Immunotherapy in Advanced Non-Small Cell Lung Cancer: A Prospective, Randomized Controlled Phase II Clinical Trial

This will see if adding focused radiation to remaining tumors helps people with advanced non‑small cell lung cancer who have up to five residual lesions after first‑line chemo‑immunotherapy.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 224 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Cancer Institute and Hospital, Chinese Academy of Medical Sciences (Academic / other)
• Drugs / interventions: chemotherapy, immunotherapy, radiation
• Locations: 1 site (Beijing, Beijing Municipality)
• Trial ID: NCT07014202 on ClinicalTrials.gov

What this trial studies

This phase 2 randomized trial compares standard maintenance immunotherapy (with or without chemotherapy) alone versus maintenance plus consolidation radiotherapy directed at all remaining lesions in adults with advanced NSCLC. Eligible patients have completed 4–6 cycles of first‑line platinum‑based chemo‑immunotherapy and show oligoresidual disease on PET‑CT (no more than five lesions in up to three organs) with ECOG 0–1 and no actionable EGFR/ALK mutations. Participants are randomized to receive either maintenance therapy alone or maintenance plus targeted radiotherapy to residual lesions, with progression‑free survival as the primary endpoint. Imaging and tumor samples are used for eligibility confirmation and correlative analyses.

Who should consider this trial

Good fit: Adults (≥18 years) with advanced NSCLC who finished 4–6 cycles of first‑line platinum‑based chemo‑immunotherapy, have ≤5 PET‑avid residual lesions in ≤3 organs, ECOG 0–1, and no actionable EGFR/ALK mutations.

Not a fit: Patients with widespread disease (>5 lesions or involvement of >3 organs), progression after initial treatment, poor performance status, or actionable driver mutations are unlikely to benefit from this approach.

Why it matters

Potential benefit: If successful, adding radiotherapy could delay disease progression and extend the time patients remain on effective therapy before needing a change in systemic treatment.

How similar studies have performed: Previous randomized and phase‑2 trials of local consolidative therapy in oligometastatic NSCLC and other cancers have shown improved progression‑free survival and sometimes overall survival, but evidence specifically after modern chemo‑immunotherapy is more limited.

Eligibility criteria

Inclusion Criteria:

1. Voluntary signed written informed consent and compliance with protocol requirements;
2. Age ≥ 18 years;
3. Expected survival time ≥ 3 months;
4. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1;
5. Histologically or cytologically confirmed advanced non-small cell lung cancer;
6. 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;
7. All residual lesions can safely receive radiation therapy as assessed by radiation oncologists;
8. Patient can tolerate the radiotherapy process, such as maintaining fixed position;
9. At least one measurable lesion among the oligoresidual lesions according to RECIST v1.1;
10. Agreement to provide archived tumor tissue specimens from primary or metastatic sites, or fresh tissue samples; if unable to provide tumor tissue samples, subjects may be enrolled after investigator assessment if meeting other inclusion/exclusion criteria;
11. Toxicities from previous anti-tumor therapies recovered to ≤ grade 1 per National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE v5.0) (excluding alopecia, fatigue, pigmentation, hypothyroidism stable on hormone replacement therapy, grade 2 peripheral neuropathy after chemotherapy, and exceptions specified in other inclusion criteria);
12. 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.

Exclusion Criteria:

1. Archived tumor tissue, pre-treatment tumor biopsy, or histological examination showing evidence of previous small cell or mixed small cell/non-small cell histology;
2. 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;
3. Symptomatic brain metastases;
4. Leptomeningeal metastases;
5. 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);
6. 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;
7. Comorbidities requiring immunosuppressive medication, or requiring systemic or local use of corticosteroids at immunosuppressive doses;
8. Pregnancy or breastfeeding;
9. Interstitial lung disease with symptomatic manifestations, or that may interfere with the detection or management of suspected drug-related pulmonary toxicity;
10. 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);
11. History of severe neurological or psychiatric disorders, including but not limited to: dementia, depression, seizures, bipolar disorder, etc.;
12. Receipt of other investigational drugs or treatments within 4 weeks prior to study randomization;
13. Use of any Chinese herbal medicines with anti-tumor activity within 2 weeks prior to study drug administration;
14. 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;
15. History of severe cardiac or cerebrovascular disease, e.g., New York Heart Association (NYHA) ≥ class 2 heart failure, acute coronary syndrome (such as myocardial infarction, unstable angina, etc.) within 6 months of screening, acute cerebrovascular disease (such as transient ischemic attack, cerebral infarction, cerebral hemorrhage, etc.) within 6 months of screening;
16. Thromboembolic events requiring therapeutic intervention within 6 months prior to screening, such as unstable deep vein thrombosis, arterial thrombosis, and pulmonary embolism; excluding infusion-related thrombosis;
17. Planned vaccination or vaccination with live vaccines within 28 days prior to study randomization;
18. Other conditions deemed unsuitable for participation in this clinical trial by the investigator due to comorbidities or other circumstances.

Where this trial is running

Beijing, Beijing Municipality

• National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College — Beijing, Beijing Municipality, China (Recruiting)

Study contacts

• Study coordinator: Zhijie Wang, MD

Conditions Non-Small Cell Lung Cancer