Low-dose intestinal radiation plus immunotherapy for immune-resistant metastatic solid cancers

Efficacy and Safety of Combining Intestinal Low Dose Radiotherapy and PD-1/PD-L1 Inhibitors for Metastatic Malignant Solid Tumors After Acquired Resistance to Anti-PD1/PD-L1 Treatment

This trial tests whether giving small doses of radiation to the intestine together with PD‑1/PD‑L1 immunotherapy can help people whose metastatic solid tumors have stopped responding to checkpoint inhibitors.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 48 (estimated)
• Ages: 18 Years to 80 Years
• Sex: All
• Sponsor: Shantou University Medical College (Academic / other)
• Drugs / interventions: chemotherapy, immunotherapy, radiation
• Locations: 1 site (Shantou, Guangdong)
• Trial ID: NCT07071103 on ClinicalTrials.gov

What this trial studies

This is a multicohort phase II trial combining intestinal low‑dose radiotherapy (ILDR) with PD‑1/PD‑L1 monoclonal antibody therapy in patients with metastatic solid tumors that progressed after prior checkpoint inhibitor treatment. Patients are enrolled into three parallel cohorts (lung cancer, esophageal cancer, and other solid tumors) with up to 16 patients per cohort and a planned total of 48 participants including those from the prior ILDR‑01 study. The trial delivers targeted low doses of radiation to the intestine to alter the gut microenvironment and immune signaling while continuing systemic PD‑1/PD‑L1 therapy, and monitors safety and antitumor activity by RECIST and clinical follow‑up. Eligible patients are adults (18–80) with ECOG 0–2, measurable disease, life expectancy ≥3 months, and no remaining standard treatment options.

Who should consider this trial

Good fit: Ideal candidates are adults (18–80) with metastatic solid tumors that have progressed on prior PD‑1/PD‑L1 therapy, have at least one measurable lesion, ECOG performance status 0–2, and no standard treatment options remaining.

Not a fit: Patients with poor performance status (ECOG >2), life expectancy under three months, those who remain candidates for standard surgical or systemic treatments, or those unable to attend the single study site are unlikely to benefit from this protocol.

Why it matters

Potential benefit: If successful, the combination could re‑sensitize resistant tumors to immunotherapy, producing tumor shrinkage or slower disease progression for patients who had stopped responding to checkpoint inhibitors.

How similar studies have performed: Preclinical data and small clinical reports indicate low‑dose radiation can modulate immunity and enhance checkpoint blockade, but large randomized evidence specifically for intestinal low‑dose radiotherapy combined with PD‑1/PD‑L1 inhibitors is currently lacking.

Eligibility criteria

Inclusion Criteria:

* Age ≥18 years, ≤80 years, regardless of gender.
* ECOG level 0-2.
* Expected life span\>3 months.
* At least one accessible and measurable lesion should be selected as the target lesion for observation according to RECIST criteria.
* Patients with metastatic solid tumors (of any histology) without standard therapy options, who have previously received immunotherapy, immunotherapy combined with chemotherapy, or immunotherapy combined with anti-angiogenesis treatment and have shown disease progression.
* Patients should not be considered eligible for surgical treatment.
* Patients with brain metastases that are assessed as clinically stable after treatment through repeated CT and/or MRI scans are eligible.
* Patients have complete clinical and pathological information.
* Patients should not be borthered by any psychological, family, social or geographical conditions that may hinder compliance with the research protocol.
* Patients should be able to understand the informed consent form, voluntarily participate, and sign the informed consent form.
* Other indicators accord with the general inclusion criteria for clinical trials.

Exclusion Criteria:

* Patients with contraindications to radiation therapy and immunotherapy.
* Previous occurrence of unacceptable immune related toxic side effects (immune myocarditis, pneumonia, etc.).
* Patients who were assessed as hyperprogressive disease (HPD).
* Patients who have received pelvic and abdominal radiation therapy within 6 months prior to enrollment.
* The adverse reactions from prior treatment have not yet recovered to a CTCAE5.0 rating of ≤ 1 (excluding toxicity that has been determined to be risk-free, such as fatigue or hair loss).
* Patients with active uncontrolled systemic bacterial, viral, or fungal infections despite optimal treatment.
* Significant liver or kidney dysfunction (i.e., laboratory values \>3 times the upper limit of normal).
* Active hepatitis B, hepatitis C, HIV, or syphilis.
* Brain disorders, symptomatic central nervous system (CNS) or meningeal metastases, or impaired cognitive function.
* Hypersensitivity to any drug included in the trial.
* Drug and/or alcohol abuse.
* Pregnant or breastfeeding women.
* Concurrent participation in another therapeutic clinical trial.
* Poorly controlled pleural effusion, pericardial effusion, or ascites requiring frequent drainage (recurrence within ≤14 days after intervention).
* Major surgery within 30 days.
* Use of antibiotics, antifungals, antivirals, antiparasitics, or probiotics within 4 weeks before enrollment.

Where this trial is running

Shantou, Guangdong

• Cancer Hospital, Shantou University Medical College — Shantou, Guangdong, China (Recruiting)

Study contacts

• Study coordinator: Chuangzhen Chen, MD

Conditions Radiotherapy; Metastatic Solid Cancers; Immune Checkpoint Blockade; Esophageal Neoplasms Malignant; Lung Neoplasm Malignant; Drug Resistance