This pilot phase I trial aims to investigate the safety and tolerability of anti-programmed cell death-1 (PD-1) monoclonal antibody Sintilimab (also called IBI308) in combination with concurrent stereotactic body radiation therapy (SBRT) and low dose radiotherapy (LDRT) in treating patients with stage IV non-small cell lung cancer (NSCLC). At least 29 participants will be enrolled in this study. All will take part at West China Hospital, Sichuan University.
This exploratory phase I study will be conducted in two steps: Step A: A low dose radiotherapy (LDRT) dose escalation, 6 patients per cohort (a total of 18 patients) will be enrolled to determine the maximum tolerated dose (MTD), dose-limiting toxicity (DLT) and recommended dose for expansion (RDE) for lung LDRT. Step B: A lung LDRT dose expansion All eligible patients will receive lung SBRT dosed at 30 Gy in 3 fractions, in combination with LDRT at different dose levels (decried as below) starting from the 2nd day of SBRT, followed by sintilimab monotherapy starting within 7 days after radiation completed. Sintilimab will be given at 200mg every 3 weeks until disease progression, unacceptable toxicities, the patient withdraws informed consent, or sintilimab reaches a maximum of up to 24 months. Patients in the dose escalation will receive lung LDRT at 3 cohorts with increasing dose levels: 2 Gy in 1 fraction in dose level 1, 4 Gy in 2 fractions in dose level 2, 10Gy in 5 fractions in dose level 3. A cohort of 17 patients will receive lung LDRT at the RDE determined during the dose escalation phase in combination with SBRT and Sintilimab to obtain additional safety and response data.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
29
Patients will receive treatment with Sintilimab 200mg every 3 weeks for a maximum of 24 months.
Radiation treatment utilized in this trial consists of SBRT with a standard doses to 30 Gy/3f
LDRT at dose escalation levels: 2 Gy/1f, 4 Gy/2f, 10 Gy/5f with conventional external beam radiation.
West China Hospital, Sichuan University
Chengdu, Sichuan, China
Number of Participants With Adverse Events and/or Dose Limiting Toxicities of Sintilimab in Combination With SBRT and LDRT
Adverse Events and/or Dose Limiting Toxicity graded per Common Terminology Criteria for Adverse Events (CTCAE) version 5.0
Time frame: from randomization through 30 days after last dosing, up to 24 months
Progression Free Survival (PFS)
Investigator assessed PFS according to RECIST v1.1. Progression free survival is defined as time of enrollment to first evidence of progressive disease. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions.
Time frame: up to 24 months after the enrollment
Objective Response Rate (ORR)
Investigator assessed ORR using RECIST v1.1 including the all tumor, the tumor undergoing LDRT and the tumor which do not receive radiotherapy. Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) for target lesions and assessed by CT: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR
Time frame: up to 24 months after the enrollment
Overall Survival (OS)
OS is defined as the difference (in months) between the date of study enrollment to the date death due to any cause
Time frame: up to 24 months after the enrollment
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