Multi-center Phase I Study of Sintilimab in Combination With Radiotherapy in Treatment Naive PD-L1 Positive Stage IV Non-small Cell Lung Cancer (NSCLC)
Phase: PHASE1
Conditions: Stage IV NSCLC
Sponsor: Sichuan University

IHC-001: Safety and Tolerability Evaluation of Sintilimab in Combination With
Radiation in Stage IV NSCLC Patients
NCT number: NCT03812549
Date: 2018.08.19
Version:1.0
Study population
Eligible patients had histologically or cytologically confirmed stage IV NSCLC; were
negative for mutations of EGFR\ALK\ROS1; were aged 18 to 75; never received any
systematic treatment (including immunotherapy, chemotherapy and targeted therapy);
had an Eastern Cooperative Oncology Group (ECOG) performance status 0–1; PD-L1
positive (TPS ≥1%); had an expected survival time ≥3 months; and presented no
major organ dysfunction Patients were excluded if they had active brain metastases,
uncontrolled
hypertension,
severe
cardiovascular
diseases,
or
coagulation
abnormalities. This study was reviewed and approved by the Institutional Review
Board of West China Hospital, Sichuan University. Written informed consent was
obtained from all participants.
This study is registered with ClinicalTrials.gov, number NCT03812549
Study design
This study is a dose-finding, phase I trial of IBI308 in combination with radiotherapy,
including dose-escalation and dose-expansion parts. Patients with untreated advanced
NSCLC will receive SBRT for small lesions, LDRT for large lesions, and IBI308
treatment every three weeks. Tumors of enrolled patients must be PD-L1 positive.
The dose-escalation part during the dose-escalation phase trial includes the
determination of DLT, MTD, and RDE for LDRT, and preliminary assessment of
safety and tolerability. The dose-expansion part of dose-expansion phase includes
continuing to expand to 17 patients based on MTD/RDE, and further observing the
safety and efficacy of this dose.
Assessments
Primary objectives:
To evaluate the safety and preliminary efficacy of IBI308 combined with radiotherapy
in the treatment of patients with stage IV PD-L1 positive NSCLC.
1.As the dose-escalation stage, dose-escalation phase mainly serves to evaluate the
safety of IBI308 combined with radiotherapy and to determine the LDRT dose.
2.Dose-expansion phase further evaluates the safety and objective response rate (ORR)
of IBI308 combined with radiotherapy.
To evaluate the safety of IBI308 combined with radiotherapy for first-line treatment
of PD-L1-positive stage IV NSCLC, including incidences of all adverse events (AEs)
and serious adverse events (SAEs), treatment-related adverse events (TRAEs), and
their severity.
Secondary objectives:

To evaluate the efficacy of IBI308 combined with radiotherapy for first-line treatment
of PD-L1-positive stage IV NSCLC, including median ORR, progression-free
survival (PFS), overall survival (OS).
Statistical analysis
All analyses were performed using R software33 (version 4.02) or Prism (version 9.0;
GraphPad Software, San Diego, CA, USA). Unless otherwise noted, two-sided 95%
confidence intervals will be adopted. Continuous variables will be summarized using
descriptive statistics including number of cases, mean, median, standard deviation,
and maximum and minimum. The numbers and percentages of cases will be described
by categories. Statistical analyses will be further explained in the statistical analysis
plan (SAP). SAP will be finalized before database lock.