NCT07071103

Intestinal Low Dose Radiotherapy Combined With Immunotherapy in Immune-resistant Metastatic Malignant Solid Tumors

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

• Status: Recruiting
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 48 (estimated)
• Sponsor: Chuangzhen Chen · Academic / Other
• Sex: All
• Age: 18 Years – 80 Years
• Healthy volunteers: Not accepted

Summary

Preclinical and clinical evidence suggests that intestinal low-dose radiotherapy (ILDR) may enhance antitumor immune responses by modulating the gut microenvironment, thereby improving the efficacy of immune checkpoint inhibitors (ICBs) in refractory solid tumors. Based on these findings, the investigators initiate a multicohort phase II clinical trial to evaluate the clinical benefit and safety of ILDR combined with PD-1/PD-L1 monoclonal antibody therapy in patients with metastatic solid tumors resistant to prior ICB treatment. In this study, patients are stratified into three parallel cohorts by tumor type (lung cancer, esophageal cancer, and other solid tumors), with 16 patients per cohort (48 in total, including subjects enrolled from the ILDR-01 study). Eligible participants includes patients with advanced metastatic solid tumors progressing after monotherapy or combination ICB treatment, meeting criteria of ECOG performance status 0-2, life expectancy ≥3 months, and have at least one measurable lesion. Exclusion criteria encompasses prior pelvic radiotherapy, ongoing infections, major organ dysfunction, or concurrent antitumor therapies. The primary endpoints includes objective response rate (ORR), disease control rate (DCR), progression-free survival after ILDR (PFS2), and the incidence of abscopal effects. Secondary endpoints includes overall survival (OS), treatment safety, α/β diversity changes in gut microbiota, peripheral blood immune cell subset dynamics, and tumor immune microenvironment remodeling characteristics. All patients receives a 1 Gy jejunoileal radiotherapy followed by PD-1/PD-L1 monoclonal antibody administration (in accordance to prior protocols or guidelines) within 24 hours, with maintenance therapy up to 2 years. Therapeutic efficacy is assessed via RECIST v1.1, while therapeutic toxicity is assessed according to CTCAE v5.0. Paired pre- and post-treatment samples (including wumor tissue, stool, peripheral blood etc.) are collected for metagenomic sequencing, metabolomic analysis, and multi-omics integrative modeling to systematically elucidate the regulation mechanism of gut microbiota-metabolite-immune axis mediated by ILDR. This approach aims to provide theoretical foundations for optimizing treatment strategies in immunotherapy-resistant tumors and identify biomarkers that potentially associated with therapeutic efficacy.

Conditions

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

Interventions

Type	Name	Description
RADIATION	Low-dose radiotherapy to the intestine (ILDR)	A single total dose of 1 Gy irradiation targeting the jejunum and ileum. Primary tumor or metastatic lesions that are within the irradiation field are irradiated concurrently.
DRUG	PD-1/PD-L1 monoclonal antibodies	Pre-progression immunotherapy regimen continues or switches to an alternative PD-1/PD-L1 monoclonal antibody according to clinical guidelines.PD-1/PD-L1 monoclonal antibody will be given 1 day after ILDR at a 3-week interval.

Timeline

• Start date: 2025-09-26
• Primary completion: 2028-01-01
• Completion: 2028-01-01
• First posted: 2025-07-17
• Last updated: 2025-11-20

Locations

1 site across 1 country: China