Safety and Tolerability of LDRT Plus Concurrent Partial SBRT and Tislelizumab in Patients with Bulky Tumors

Phase 1

Recruiting

• Conditions: Solid Tumor
• Interventions: Drug: Tislelizumab; Radiation: Low Dose Radiotherapy; Radiation: Stereotactic Ablative Radiotherapy

• Registration Number: NCT06349837
• Lead Sponsor: Sichuan University

Brief Summary

This is a 3+3 dose escalation phase I study which aims to evaluate the safety and tolerability of low dose radiotherapy (LDRT) plus concurrent partial Stereotactic Ablative Radiotherapy (SBRT) and Tislelizumab in Patients with bulky tumors who have failed standard therapy. At least 9 participants will be enrolled in this study.

Detailed Description

This is 3+3 escalation phase I study which will be conducted in West China Hospital.

3 patients per cohort (a total of 9 patients) will be enrolled to observe the dose-limiting toxicity (DLT) and recommended dose for expansion (RDE) for lung LDRT and partial SBRT.

All eligible patients will receive LDRT + partial SBRT and Tislelizumab at different dose levels (decried as below). Tislelizumab will be given at 200mg as recommended in the instruction manual every 3 weeks until disease progression, unacceptable toxicities, the patient withdraws informed consent, or Tislelizumab reaches a maximum of up to 24 months. Patients in the dose escalation will receive LDRT + partial SBRT at 3 cohorts with increasing dose levels: 6 Gy (2 Gy/f) + 24 Gy (8 Gy/f); 6 Gy (2 Gy/f) + 30 Gy (10 Gy/f); 6 Gy (2 Gy/f) + 45 Gy (15 Gy/f).

Study Timeline

• Study First Submitted: 2024-03-31
• Study First Submitted QC: 2024-04-04
• Study First Posted: 2024-04-05
• Study Start: 2024-04-18
• Status Verified: 2024-08
• Last Update Submitted: 2025-02-27
• Last Update Posted: 2025-03-04
• Primary Completion: 2026-03-31
• Study Completion: 2026-11-30

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 9

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. 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. Known allogeneic organ transplantation (except corneal transplantation) or allogeneic hematopoietic stem cell transplantation.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
LDRT+SBRT + Tislelizumab	Low Dose Radiotherapy	This is a dose escalation study, low Dose Radiotherapy (LDRT) dose was 6Gy/3f, Stereotactic Ablative Radiotherapy (SBRT) dose was 24Gy/3f , 30Gy/3f and 45 Gy/3f, the dose of Tislelizumab was recommended in the instruction manual.
LDRT+SBRT + Tislelizumab	Stereotactic Ablative Radiotherapy	This is a dose escalation study, low Dose Radiotherapy (LDRT) dose was 6Gy/3f, Stereotactic Ablative Radiotherapy (SBRT) dose was 24Gy/3f , 30Gy/3f and 45 Gy/3f, the dose of Tislelizumab was recommended in the instruction manual.
LDRT+SBRT + Tislelizumab	Tislelizumab	This is a dose escalation study, low Dose Radiotherapy (LDRT) dose was 6Gy/3f, Stereotactic Ablative Radiotherapy (SBRT) dose was 24Gy/3f , 30Gy/3f and 45 Gy/3f, the dose of Tislelizumab was recommended in the instruction manual.

Primary Outcome Measures

Name	Time	Method
Dose Limiting Toxicities	24 months

Secondary Outcome Measures

Name	Time	Method
Progression Free Survival (PFS)	up to 24 months after the enrollment	Investigator assessed PFS according to RECIST v1.1. Progression free survival is defined as time of enrollment to first evidence of progressive disease.
Objective Response Rate (ORR)	up to 24 months after the enrollment	The Objective Response Rate (ORR) is the percentage of participants who achieved a best overall response of Complete Response (CR) or Partial Response (PR) based on RECIST version 1.1.
Overall Survival (OS)	up to 24 months after the enrollment	OS is defined as the difference (in months) between the date of study enrollment to the date death due to any cause

Trial Locations

Locations (1)

West China Hospital, Sichuan University; 🇨🇳 Chengdu, Sichuan, China