Combining low dose radiotherapy with PD-1 inhibitors for advanced lung cancer

Phase I Study of Low Dose Radiotherapy and Concurrent SBRT in Combination With PD-1 Inhibitors in Advanced Non-small Cell Lung Cancer (NSCLC) .

This study is testing a new treatment that combines low dose radiation with PD-1 inhibitors to see if it can help patients with advanced lung cancer who haven't responded to other treatments.

Quick facts

• Phase: Phase 1
• Study type: Interventional
• Enrollment: 9 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Sichuan University (Academic / other)
• Drugs / interventions: chemotherapy, immunotherapy, radiation
• Locations: 1 site (Chengdu, Sichuan)
• Trial ID: NCT05615142 on ClinicalTrials.gov

What this trial studies

This pilot phase I trial investigates the safety and tolerability of low dose radiotherapy (LDRT) combined with partial stereotactic body radiation therapy (SBRT) and PD-1 inhibitors in patients with stage IV non-small cell lung cancer (NSCLC) who have not responded to standard therapies. The study will enroll at least 9 participants at West China Hospital, Sichuan University, using a dose escalation approach to determine the maximum tolerated dose and any dose-limiting toxicities. Participants will receive LDRT and SBRT at varying doses, followed by PD-1 inhibitors starting within a week after radiation treatment. The goal is to assess the safety profile of this combination therapy in a challenging patient population.

Who should consider this trial

Good fit: Ideal candidates are adults aged 18 and older with histologically confirmed stage IV NSCLC who have failed standard treatment.

Not a fit: Patients with early-stage NSCLC or those who have not yet undergone standard therapies may not benefit from this study.

Why it matters

Potential benefit: If successful, this approach could provide a new treatment option for patients with advanced NSCLC who have exhausted standard therapies.

How similar studies have performed: While there is ongoing research in combining radiotherapy with immunotherapy, this specific approach is novel and has not been extensively tested.

Eligibility criteria

Inclusion Criteria:

1. Be willing and able to provide written informed consent/assent for the trial.
2. Be ≥18 years of age on day of signing informed consent.
3. Patients with histologically or cytologically confirmed stage IV NSCLC.
4. Be willing to undergo repeat biopsy of tumor lesions according to the study protocol.
5. Patients who have failed the standard therapy, or who are unsuitable for standard treatment, or refuse chemotherapy.
6. At least one measurable lesion according to RECIST 1.1. A lesion that has previously received radiotherapy can be considered a target lesion only if this lesion is clearly progressed after radiotherapy.
7. The target lesions (irradiated lesions) are \> 5cm in in diameter
8. ECOG 0-2.
9. Life expectancy of \> 3 months.
10. Patients must have normal organ and bone marrow function as defined below: Total bilirubin \</= 1.5 x upper limit of normal (ULN). Aminotransferase (AST) Serum Glutamic Oxaloacetic Transaminase (SGOT)/ Alanine Aminotransferase (ALT) Serum Glutamic-Pyruvic Transaminase (SGPT) \<2.5 X institutional upper limit of normal (\</= 5 X institutional ULN for subjects with liver metastases) \*WBC \>/= 3500/uL, ANC \>/= 1500/uL \*Platelets \>/= 90K/ul \*Hemoglobin \>/= 9g/dL \*Creatinine \</= 1.5 x ULN, or creatinine clearance ≥ 50 ml/min（Cockcroft-Gault equation）. Coagulation: International Normalized Ratio (INR)≤ 1.5 × ULN, Partial thromboplastin time (PTT) ≤1.5 × ULN; left ventricular ejection fraction (LVEF) \>/= 50% and QTcF (Fridericia's formula) ≤ 450ms
11. Patients has recovered (i.e., ≤ Grade 1 or at baseline) from adverse events due to a previously administered agent.
12. Wash out period for chemotherapy is more than ≥ 4 weeks, for targeted small molecule therapy ≥ 5 half-lives; palliative radiotherapy must have been completed for at least ≥ 2 weeks, chest radiotherapy must have been completed for at least ≥ 4 weeks, and major surgery must have been completed for ≥ 4 weeks.
13. Subjects with no severe pulmonary ventilation dysfunction, no acute heart failure, and no contraindication to radiotherapy as judged by the radiotherapist. Subjects who agree to receive immunotherapy and radiotherapy treatment.
14. Subjects should agree to use an adequate method of contraception.

Exclusion Criteria:

1. Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis and/or spinal cord compression, etc.
2. With oncologic emergencies that require immediate treatment
3. EGFR/ALK/ROS-1 mutation or mutation status unknown.
4. Has evidence of interstitial lung disease or active and/or non-infectious pneumonitis (drug-induced pneumonia, radiation-induced pneumonia, etc.) requiring steroid therapy.
5. History of pulmonary fibrosis, pulmonary hypertension, severe irreversible airway obstruction disease
6. Patients with peripheral neuropathy.
7. Significant heart disease or impairment of cardiac function
8. Fluid accumulating in the third space, such as pericardial effusion, pleural effusion and peritoneal effusion that remains uncontrolled by aspiration or other treatment
9. Known allergy to drugs or excipients, known severe allergic reaction to any of the PD-1 monoclonal antibodies
10. Severe infection within 4 weeks prior to the start of study treatment, including but not limited to hospitalization for infection, bacteremia, or severe pneumonia; treatment with oral or intravenous antibiotics within 2 weeks prior to the start of study treatment; patients receiving prophylactic antibiotic therapy (e.g., to prevent urinary tract infection or exacerbation of COPD) are eligible for this study.
11. Known or suspected active autoimmune disease (congenital or acquired) such as uveitis, enterocolitis, hepatitis, pituitary inflammation, vasculitis, nephritis, thyroiditis, etc. (patients with vitiligo, or resolved childhood asthma may be enrolled; patients with type I diabetes with good insulin control may also be enrolled)
12. Known allogeneic organ transplantation (except corneal transplantation) or allogeneic hematopoietic stem cell transplantation.

Where this trial is running

Chengdu, Sichuan

• West China Hospital, Sichuan University — Chengdu, Sichuan, China (Recruiting)

Study contacts

• Principal investigator: You Lu, MD — West China Hospital
• Study coordinator: You Lu, MD

Conditions NSCLC; Low Dose Radiotherapy; Stereotactic Body Radiotherapy; PD-1 Inhibitor