Boosting immunotherapy with low-dose liver radiation

PRIME-LRT: PRomoting IMmunotherapy Efficacy With Low-Dose Liver RT

This trial tests whether adding low-dose radiation to the liver before immunotherapy helps people with melanoma or non-small cell lung cancer who have liver metastases live longer without their disease worsening.

Quick facts

• Phase: Not applicable
• Study type: Interventional
• Enrollment: 21 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: University of Cincinnati (Academic / other)
• Drugs / interventions: chemotherapy, immunotherapy, radiation
• Locations: 1 site (Cincinnati, Ohio)
• Trial ID: NCT07225036 on ClinicalTrials.gov

What this trial studies

Adults with melanoma or non-small cell lung cancer and radiographic liver metastases will continue standard PD‑1/PD‑L1 immunotherapy (with or without standard chemotherapy) while receiving low‑dose liver radiation (LD‑LRT) before treatment cycles 1, 2, and 3. The study runs two parallel cohorts (NSCLC and melanoma) and uses Simon’s optimal two‑stage design to compare 6‑month progression‑free survival (PFS) in each cohort against historical benchmarks, targeting a 25% absolute improvement. The primary endpoint is 6‑month PFS evaluated separately for each cohort, and LD‑LRT is the only investigational intervention added to standard care. The trial is conducted at a single site (University of Cincinnati Medical Center) and will enroll patients who meet performance status and organ function criteria.

Who should consider this trial

Good fit: Adults (≥18) with biopsy‑proven NSCLC or melanoma, radiographic liver metastases, ECOG ≤2 (or Karnofsky ≥60%), adequate organ function, and planned treatment with a PD‑1/PD‑L1 immunotherapy regimen are the intended participants.

Not a fit: Patients without liver metastases, not receiving PD‑1/PD‑L1 immunotherapy, with poor performance status, or with contraindications to liver radiation are unlikely to benefit from this intervention.

Why it matters

Potential benefit: If successful, LD‑LRT could increase time without disease progression at six months and potentially improve survival and quality of life for patients with liver metastases receiving immunotherapy.

How similar studies have performed: Preclinical studies and small clinical reports suggest liver‑directed radiation can alter the immune microenvironment and enhance systemic immunotherapy, but this specific low‑dose liver RT approach in defined NSCLC and melanoma cohorts remains relatively novel.

Eligibility criteria

Inclusion Criteria:

1. Age ≥18 years.
2. ECOG performance status ≤2 (or Karnofsky ≥60%, see Appendix A).
3. Patients must have adequate organ and marrow function to receive standard of care immunotherapy and/or chemoimmunotherapy as per the treating medical oncologist.
4. Must be planning to, and able to, undergo active treatment with PD-L1 or PD-1 checkpoint immunotherapy given per standard care throughout the duration of the RT intervention per their treating physician.

   • Note: Patients may receive other SOC CTLA 4 inhibitors or other SOC chemotherapy/immunotherapy in combination with a SOC PD-L1 or PD-1 checkpoint inhibitor and remain eligible.
5. Biopsy proven Non-Small Cell Lung Cancer (NSCLC) or Melanoma.
6. Radiographic evidence of liver metastases.
7. Women of child-bearing potential and men must agree to use adequate contraception (e.g., hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation.
8. Ability to understand and the willingness to sign a written informed consent document. Legally authorized representatives may sign and give informed consent on behalf of study participants.
9. Patients must have insurance authorization to proceed with radiotherapy prior to initiation of radiation treatment on study

Exclusion Criteria:

1. Patients with prior immunotherapy use in the adjuvant setting for NSCLC or Melanoma are eligible unless the adjuvant immunotherapy was delivered within 6 months of enrollment.
2. Patients with NSCLC are ineligible for enrollment in cohort 1 if the presence of the following driver mutations are noted: EGFR, ALK, ROS1, RET.
3. Patients with uncontrolled intercurrent illness or any other significant condition(s) that would make participation in this protocol unreasonably hazardous, in the opinion of the Investigator.
4. Patients with a prior or concurrent malignancy whose natural history or treatment has the potential to interfere with the safety or efficacy assessment of the investigational regimen in the opinion of the Investigator.
5. Pregnant women are excluded from this study considering the use of ionizing radiation.

Where this trial is running

Cincinnati, Ohio

• University of Cincinnati Medical Center — Cincinnati, Ohio, United States (Recruiting)

Study contacts

• Study coordinator: UCCC Clinical Trials Office

Conditions Low-Dose Liver Radiation; Non Small Cell Lung Cancer; Melanoma; Liver Metastases