Finding the best organ-targeted radiotherapy plus chemo and PD-1 combinations to trigger abscopal responses in metastatic non-small cell lung cancer without EGFR/ALK mutations

A Prospective, Multicenter, Umbrella Design Clinical Study on the Abscopal Effect Induced by Different Radioimmunotherapy Combination Patterns in the Treatment of Non-Small Cell Lung Cancer With Multiple Metastases

This study will try different combinations of radiotherapy, chemotherapy, and PD‑1 immunotherapy to see if they trigger whole-body (abscopal) tumor responses and improve outcomes for people with metastatic NSCLC who do not have EGFR or ALK mutations.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 427 (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: NCT06947694 on ClinicalTrials.gov

What this trial studies

This Phase 2, multicenter umbrella trial tests several radioimmunotherapy combination patterns and different organ-target radiotherapy pairings in patients with stage IV non‑small cell lung cancer lacking common driver mutations. Patients receive chemotherapy plus PD‑1 inhibitors alongside targeted radiotherapy to one or more organs according to assigned arms to identify which patterns produce abscopal (distant) tumor responses. The study will collect multimodal omics data and apply machine learning to build a predictive model of the abscopal effect and to explore immune and organ-specific biomarkers. Primary endpoints include survival and occurrence of abscopal responses, with safety and feasibility monitored across arms.

Who should consider this trial

Good fit: Adults 18–75 with stage IV NSCLC who are negative for driver genes (EGFR, ALK, ROS, BRAF, MET, RET), have 3–6 metastatic lesions, ECOG 0–1, no active brain metastases (or stable lesions), and are eligible for chemo, PD‑1 therapy, and radiotherapy.

Not a fit: Patients with actionable driver mutations, more than six metastases, uncontrolled brain metastases, severe organ dysfunction, other active malignancies, or ECOG >1 are unlikely to qualify or benefit from this protocol.

Why it matters

Potential benefit: If successful, the approach could increase survival and produce tumor shrinkage outside the radiation field by identifying optimal organ-targeting and therapy combinations.

How similar studies have performed: Prior case reports and early‑phase studies have shown occasional abscopal responses when combining radiotherapy and immunotherapy, but findings are inconsistent and reliable predictive biomarkers are not established.

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 diagnosed initially through pathological histology.
  2. There are 3-6 metastatic lesions.
  3. No brain metastasis or the lesions are stable.
  4. Negative for driver genes (including EGFR, ALK, ROS, BRAF, MET, RET genes. Note: The above English terms are all gene names).
  5. ECOG (Eastern Cooperative Oncology Group) score: 0-1 point, with an expected, survival period of more than 3 months.
  6. Aged between 18 and 75 years old.
  7. Evaluated by PET-CT (including FDG and FMISO, not mandatory).
  8. No contraindications for immunotherapy and radiotherapy.
  9. The informed consent form has been signed.

Exclusion Criteria:

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

  1. Those with severe dysfunction of vital organs (heart, liver, kidney).
  2. Those accompanied by other malignant tumors.
  3. Those with uncontrolled heart diseases or having experienced a myocardial infarction within the past six months.
  4. Those with a history of mental illness.
  5. And other situations in which the researchers deem it inappropriate for the subjects 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