Optimal combination of radiotherapy schedules and Benmelstobart to induce abscopal responses in metastatic NSCLC

An Umbrella Trial of Combining Different Radiotherapy Fractionation Patterns With Immunotherapy for Multiple Metastases of Non-Small Cell Lung Cancer

This study will test whether different radiotherapy schedules given with Benmelstobart can cause shrinking of untreated tumors (the abscopal effect) in people with stage IV NSCLC who do not have EGFR/ALK mutations and have multiple metastases.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 366 (estimated)
• Ages: 18 Years to 75 Years
• Sex: All
• Sponsor: Xinqiao Hospital of Chongqing (Academic / other)
• Drugs / interventions: immunotherapy
• Locations: 1 site (Chongqing, Chongqing Municipality)
• Trial ID: NCT06953843 on ClinicalTrials.gov

What this trial studies

This is a prospective, multicenter, phase 2 umbrella trial comparing different radiotherapy fractionation patterns combined with the immunotherapy agent Benmelstobart, often given alongside chemotherapy, to see which approach best controls untreated (abscopal) lesions. The primary objective is to compare control rates of abscopal lesions across the different radiotherapy schedules. Key eligibility includes pathologically confirmed NSCLC, more than three metastatic lesions, absence of actionable driver mutations, performance status 0–1, age 18–75, and no active brain metastases. Optional imaging such as PET-CT (FDG and FMISO) may be used for assessment and patients must have no contraindications to immunotherapy or radiotherapy.

Who should consider this trial

Good fit: Adults 18–75 with pathologically confirmed stage IV NSCLC without EGFR/ALK (and other driver) mutations, more than three metastatic lesions, ECOG/PS 0–1, no active brain metastases (or stable lesions), and no contraindications to immunotherapy or radiotherapy.

Not a fit: Patients with activating driver mutations, uncontrolled severe organ dysfunction, recent myocardial infarction, other active malignancies, poor performance status, or active brain metastases are unlikely to benefit or be eligible for this protocol.

Why it matters

Potential benefit: If successful, the regimen could provide a relatively low-toxicity way to shrink distant metastatic tumors and improve overall disease control for patients with widespread, driver-negative NSCLC.

How similar studies have performed: Small studies combining radiotherapy with immune checkpoint inhibitors have reported occasional abscopal responses, but consistent, reproducible control of distant lesions is not established and the specific Benmelstobart plus fractionation strategies tested here are relatively novel.

Eligibility criteria

Inclusion Criteria:

* Patient must meet all of the following inclusion criteria to be enrolled in this study:

  1. Non-small cell lung cancer confirmed by pathological histology.
  2. More than 3 metastatic lesions.
  3. No brain metastases or stable lesions.
  4. Negative for driver genes (including EGFR, ALK, ROS, BRAF, MET, RET).
  5. Performance status (PS) score of 0-1, with an expected survival period of more than 3 months.
  6. Age between 18 and 75 years old.
  7. Assessment by PET-CT (including FDG and FMISO, not mandatory).
  8. No contraindications to immunotherapy and radiotherapy.
  9. Signed the informed consent form.

Exclusion Criteria:

* Patients with any of the following criteria are not eligible for enrollment in this study:

  1. Those with severe dysfunction of important vital organs (heart, liver, kidney).
  2. Those accompanied by other malignant tumors.
  3. Uncontrolled heart diseases or myocardial infarction within the past 6 months.
  4. Those with a history of mental illness.
  5. Other situations in which the researcher deems it inappropriate for the subject to participate in the study.

Where this trial is running

Chongqing, Chongqing Municipality

• the second affiliated hospital of Army medical university — Chongqing, Chongqing Municipality, China (Recruiting)

Study contacts

• Principal investigator: Jianguo Sun, MD — the second affiliated hospital of Army medical university, Chongqing, Chongqing 40037 Recruiting
• Study coordinator: Jianguo Sun, MD

Conditions NSCLC Stage IV Without EGFR/ALK Mutation