This study is a prospective single-center Phase I clinical study in patients with EGFR/ALK/ROS1 driver oncogene negative, and advanced or metastatic NSCLC. This study is to evaluate the efficacy and safety preliminarily in a small-size of propranolol hydrochloride in combination with sintilimab and platinum-based chemotherapy in first-line therapy. Propranolol hydrochloride is a beta- adrenergic blocking agent which is associated with augment of immune cell responses. Propranolol hydrochloride may improve the responses of immune checkpoint inhibitors in treating patients with advanced NSCLC.
Sign a written informed consent prior to any research-related procedure
Age ≥18 years and ≤ 75 years old
ECOG PS score of 0-1
Expected survival time ≥ 12 weeks
Concurrent participation in another interventional clinical study or receipt of another investigational drug, unless participating in an observational clinical study
Prior exposure to any anti-PD-1 or anti-PD-L1, PD-L2, CD137, CTLA-4 antibody therapy, or any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways
Systemic therapy with proprietary Chinese medicines with anti-tumor indications or immunomodulatory drugs (including thiopeptides, interferons, interleukins, except those used locally for the control of hydrothorax or ascites) within 2 weeks prior to the first dose
Current use of oral or intravenous beta-blockers (e.g., atenolol, bisoprolol, carvedilol, labetalol, metoprolol, nadolol, sotalol, etc.) cannot be safely switched to a non-beta-blocker
Single group
Propranolol hydrochloride
Drug10 mg, PO, BID, for up to 2 years until disease progression/intolerable toxicity/withdrawal of informed consent.
Sintilimab
Drugintravenous infusion (IV), 200 mg, Day1, Q3W, for up to 2 years until disease progression/intolerable toxicity/withdrawal of informed consent.
Chemotherapy
DrugPlatinum-based chemotherapy: For non-squamous cell carcinoma options: carboplatin/cisplatin + pemetrexed; For squamous cell carcinoma: carboplatin/cisplatin + paclitaxel/gemcitabine. Carboplatin: IV, AUC 5, Day1, Q3W; Cisplatin: IV, 75 mg/m2, Day1-3, Q3W; Pemetrexed: IV, 500 mg/m2, Day1, Q3W; Paclitaxel: IV, 175 mg/m², Day1, Q3W; Albumin-bound paclitaxel: IV, 100 mg/m², Day1, 8, 15; or 260 mg/m2, Q3W; Gemcitabine: IV, 1000mg/m2, Day1, 8, Q3W; After 4-6 cycles of sintilimab and platinum-based chemotherapy, the patients of non-squamous cell carcinoma will be received with sintilimab and pemetrexed for maintenance therapy, for up to 2 years until disease progression/intolerable toxicity/withdrawal of informed consent.
Objective Response Rate (ORR)
The proportion of patients with a complete response or partial response to treatment according to Response Evaluation Criteria in Solid Tumors (RECIST v1.1)
Disease Control Rate (DCR)
Disease Control Rate (DCR) The proportion of patients with a complete response or partial response or stable disease to treatment according to Response Evaluation Criteria in Solid Tumors (RECIST v1.1)
Adverse events (AEs)
Based on the physical examination, vital signs, laboratory findings, and medical examinations, and record the type, incidence, severity of AEs, which were graded by Common Terminology Criteria for Adverse Events (CTCAE) v5.0
Progression-free survival (PFS)
Time from the beginning of intervention to the first disease progression (PD)
Overall survival (OS)
Time from the beginning of intervention until death due to any cause
Quality of life (QoL)
Assessed by QLQ-C30
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Second Xiangya Hospital of Central South University
Lead sponsor
Innovent Biologics (Suzhou) Co. Ltd.
Collaborator
