Propranolol Hydrochloride in Combination With Sintilimab and Platinum-based Chemotherapy for Treatment of Advanced Non-small Cell Lung Cancer

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

There are contraindications to the use of beta-blockers:

1. Hypersensitivity to any of the components of the product.

2. Bronchial asthma or risk of bronchospasm.

3. Ketoacidosis and metabolic acidosis.

4. Severe or symptomatic bradycardia (resting heart rate ≤55bpm), atrioventricular block (degrees II and III), sinus block, sick sinus node syndrome.

5. Cardiogenic shock

6. Right heart insufficiency due to pulmonary hypertension.

7. Congestive heart failure (class III or IV).

8. Hypotension (systolic blood pressure \< 100 mmHg).

9. Prolonged fasting.

10. Severe peripheral circulatory failure (e.g., gangrene).

11. Symptomatic peripheral arterial disease or Raynaud's syndrome, untreated pheochromocytoma.

12. Unstable angina or variant angina.

13. Patients on rizatriptan benzoate.

14. Severe asthma or chronic obstructive pulmonary disease (COPD)

15. Uncontrolled type I or type II diabetes mellitus (glycosylated hemoglobin \[HbA1C\] \> 8.5 or fasting blood glucose \> 160 mg/dl at screening).

16. Current use or within the last 2 years of a non-dihydropyridine calcium channel blocker (NDCCB)

Hepatic encephalopathy, hepatorenal syndrome or Child-Pugh class B or more severe cirrhosis

Tumor-related intestinal obstruction (within 3 months prior to the signing of the informed consent) or history of inflammatory bowel disease or extensive bowel resection (partial colectomy or extensive small bowel resection with chronic diarrhea), Crohn's disease, ulcerative colitis

Completion of palliative radiotherapy within 7 days prior to the first dose of study drug

With clinically active diverticulitis, abdominal abscess, gastrointestinal obstruction

History of psychotropic substance abuse or addiction

Known hypersensitivity to the active ingredients or excipients of the study drug

Known history of primary immunodeficiency or undergoing systemic glucocorticoid therapy or any other form of immunosuppressive therapy

Use of immunosuppressive drugs, excluding topical glucocorticoids by nasal, inhalational or other routes or physiological doses of systemic glucocorticoids (i.e., no more than 10 mg/day of prednisone or an equivalent dose of other glucocorticoids), or use of hormones for the prevention of contrast sensitization, within 4 weeks prior to the first dose of study treatment

Failure to recover adequately from any intervention-induced toxicity and/or complications (≤ grade 1 or baseline, excluding weakness or alopecia) prior to initiation of treatment

Receipt of live attenuated influenza vaccine within 4 weeks prior to the first dose of study treatment or planned for the duration of the study (inactivated injectable viral vaccine against seasonal influenza is permitted up to 4 weeks prior to the first dose; however, live attenuated influenza vaccine is not permitted)

Major surgery (craniotomy, thoracotomy, or laparotomy) within 4 weeks prior to the first dose of study treatment or anticipation of major surgery during study treatment; laparoscopic exploratory surgery within 2 weeks prior to the first dose of study treatment

Known symptomatic CNS metastases and/or carcinomatous meningitis. Subjects with previously treated brain metastases may be enrolled in the trial if they are clinically stable (no evidence of imaging progression for at least 4 weeks prior to the first dose of the experimental treatment, no evidence of new brain metastases or increase in size of pre-existing brain metastases as confirmed by repeat imaging) and do not require steroid therapy for at least 14 days prior to the first dose of the experimental treatment. This exception does not include carcinomatous meningitis, which should be excluded regardless of whether it is clinically stable.

Presence of clinically uncontrolled pleural effusion or ascites (subjects may be recruited who do not require drainage of the effusion or who do not have a significant increase in the effusion after 3 days of cessation of drainage)

Patients with bone metastases at risk of paraplegia

Known or suspected autoimmune disease or history of such disease within the last 2 years (patients with vitiligo, psoriasis, alopecia areata or Graves' disease not requiring systemic treatment within the last 2 years, hypothyroidism requiring only thyroid hormone replacement therapy, and type I diabetes mellitus requiring only insulin replacement therapy may be enrolled)

Known to have active tuberculosis.

A history of allogeneic organ transplants and allogeneic hematopoietic stem cell transplants is known

Known history of human immunodeficiency virus (HIV) infection (HIV-positive)

Known acute or chronic active hepatitis B virus (HBsAg-positive and HBVDNA viral load ≥200 IU/mL or ≥10\^3 copies/mL) or acute or chronic active hepatitis C virus (HCV antibody-positive and HCV RNA-positive)

Active syphilis infection requiring treatment

Suffer from interstitial lung disease requiring steroid hormone therapy

Serious infections that are active or poorly controlled clinically

Severe cardiovascular disease (e.g., myocardial infarction, arterial thromboembolism, cerebrovascular thromboembolism); angina pectoris requiring treatment; symptomatic peripheral vascular disease; NYHA cardiac class 3 or 4 congestive heart failure; or uncontrolled ≥class 3 hypertension (diastolic blood pressure ≥100 mm Hg or systolic blood pressure ≥160 mm Hg) despite antihypertensive treatment

History of other primary malignancies within 5 years, except：

1. malignancies that have been in complete remission for at least 2 years prior to enrolment and for which no other treatment was required during the study period.

2. adequately treated non-melanoma skin cancer or malignant nevus with no evidence of disease recurrence.

3. adequately treated carcinoma in situ without evidence of disease recurrence

Female patients who are pregnant or breastfeeding

Other acute or chronic medical conditions, psychiatric disorders, or abnormal laboratory test values that may result in increased risk associated with study participation or administration of study medication, or interfere with the interpretation of study results, and that, in the investigator's judgement, classify the patient as ineligible for participation in this study.

What this study is about