Propranolol Hydrochloride Combined With Toripalimab and Platinum-based Chemotherapy in Resectable Non-Small Cell Lung Cancer

NCT07886229 | Recruiting Phase 1

• 1 other identifier: LYG20260084
• Study Type: interventional
• Target: 9
• Locations: 1 country
• Sites: 4

Brief Summary

This is a prospective, multicenter, open-label study designed to evaluate the safety and tolerability of propranolol hydrochloride in combination with toripalimab and platinum-based chemotherapy as perioperative treatment in patients with resectable non-small cell lung cancer (NSCLC). 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 resectable NSCLC.

Conditions

Resectable Non-Small-Cell Lung Cancer

Keywords

Non-Small Cell Lung Cancer; Resectable NSCLC; Propranolol; Beta-Adrenergic Blocker; Toripalimab; Immune Checkpoint Inhibitor; Perioperative Therapy

Outcome Measures

Primary Outcomes (2)

• Incidence of Dose-Limiting Toxicities (DLTs)

  The number and percentage of participants experiencing dose-limiting toxicities at each propranolol dose level during the protocol-defined DLT assessment period. DLTs will be used to guide dose escalation in the conventional 3+3 design.

  Day 1 through Day 21

• Incidence and Severity of Adverse Events (AEs)

  The number and percentage of participants experiencing adverse events (AEs), treatment-emergent adverse events (TEAEs), serious adverse events (SAEs), and immune-related adverse events (irAEs). Severity will be graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE), version 5.0.

  Through study completion, up to 12 months

Secondary Outcomes (4)

• Recommended Phase II Dose (RP2D) of Propranolol

  Through study completion, up to 12 months

• Pathological Complete Response (pCR) Rate

  Perioperative

• Major Pathological Response (MPR) Rate

  Perioperative

• Objective Response Rate (ORR)

  Up to 6 months

Study Arms (1)

Propranolol Plus Toripalimab and Platinum-Based Chemotherapy

EXPERIMENTAL

Patients will receive propranolol hydrochloride in combination with toripalimab and platinum-based chemotherapy as neoadjuvant treatment for 3-4 cycles, followed by multidisciplinary evaluation for surgical resection. A conventional 3+3 dose-escalation design will be used to evaluate three dose levels of oral propranolol hydrochloride (10 mg BID, 10 mg TID, and 20 mg BID) to determine the recommended Phase II dose (RP2D). Following surgery, patients will receive postoperative maintenance treatment with propranolol hydrochloride and toripalimab according to the study protocol.

Drug: Propranolol Hydrochloride; Drug: Toripalimab; Drug: Chemotherapy

Interventions

Propranolol Hydrochloride DRUG

Oral propranolol hydrochloride will be administered at escalating dose levels using a conventional 3+3 dose-escalation design. Three planned dose levels are 10 mg BID, 10 mg TID and 20 mg BID. Propranolol will be administered in combination with neoadjuvant toripalimab and platinum-based chemotherapy, followed by postoperative maintenance treatment with propranolol and toripalimab.

Also known as: Inderal

Propranolol Plus Toripalimab and Platinum-Based Chemotherapy

Toripalimab DRUG

Toripalimab will be administered intravenously at a dose of 240 mg on Day 1 of each 21-day cycle, in combination with propranolol hydrochloride and platinum-based chemotherapy for 3-4 neoadjuvant cycles. Following surgical resection, toripalimab will be continued as postoperative maintenance therapy according to the study protocol.

Also known as: JS001

Propranolol Plus Toripalimab and Platinum-Based Chemotherapy

Chemotherapy DRUG

Participants will receive platinum-based doublet chemotherapy selected according to tumor histology. For nonsquamous NSCLC, chemotherapy will consist of pemetrexed in combination with cisplatin or carboplatin. For squamous NSCLC, chemotherapy will consist of a taxane (paclitaxel, nab-paclitaxel, liposomal paclitaxel, paclitaxel polymeric micelles, or docetaxel) in combination with cisplatin or carboplatin. Chemotherapy will be administered intravenously every 3 weeks for 3-4 neoadjuvant cycles, in combination with propranolol hydrochloride and toripalimab, followed by multidisciplinary evaluation for surgical resection.

Also known as: Platinum-Based Doublet Chemotherapy

Propranolol Plus Toripalimab and Platinum-Based Chemotherapy

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Sign a written informed consent form before any research-related procedures；
• Age ≥ 18 years and ≤ 75 years；
• ECOG PS score 0-1；
• Have self-awareness, be willing and have the ability to complete the questionnaire (stress score for all patients)；
• Provide a signed and dated written informed consent form before any mandatory research-specific procedures, sample collection and analysis；
• Histologically or cytologically confirmed operable stage II-IIIB (N2) non-small cell lung cancer (AJCC 9th edition TNM lung cancer staging）；
• Requires MDT assessment for the feasibility of radical surgery；
• No previous anti-tumor treatment, and histological specimens confirmed no EGFR gene sensitive mutations, ALK gene fusion or ROS1 gene fusion；
• According to the Response Evaluation Criteria in Solid Tumors (RECIST 1.1 version), at least one measurable lesion by imaging. Lesions located within the previous radiotherapy field can be considered measurable if progression is confirmed (within 28 days before the first treatment)；
• Agree to undergo standard lobectomy/systemic lymph node dissection；
• Meet the following laboratory indicators (14 days before the first treatment): 1) Blood routine: Absolute neutrophil count ≥ 1.5 × 109/L；Platelet count ≥ 100 × 109/L；Hemoglobin content ≥ 9.0 g/dL (no blood transfusion or no erythropoietin-dependent administration within 7 days). 2) Liver function: Total bilirubin (TBIL) ≤ 1.5 × upper limit of normal (ULN)；No liver metastasis；Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 2.5 × ULN. For patients with liver metastasis, ALT or AST ≤ 5 × ULN. 3) Kidney function: Serum creatinine (Cr) ≤ 1.5 × ULN or Cr clearance rate ≥ 60 mL/min (Cockcroft-Gault formula), and urine routine test shows urine protein (UPRO) \< 2+ or 24-hour urine protein quantification \< 1 g. 4) Coagulation function: Within 7 days before the study treatment, International Normalized Ratio (INR) ≤ 1.5 × ULN or Prothrombin Time (PT) ≤ 1.5 × ULN；if the subject is receiving anticoagulation treatment, as long as the PT is within the range of the anticoagulant drug, it is acceptable；
• Cardiac function: American Heart Association (NYHA) classification \< 3；Left ventricular ejection fraction ≥ 50%；Baseline electrocardiogram shows no PR interval prolongation or atrioventricular block；
• For pregnant women of reproductive age, a urine or serum pregnancy test should be performed 3 days before the first administration of the study drug (day 1 of the 1st cycle) and the result should be negative. If the urine pregnancy test result cannot be confirmed as negative, a blood pregnancy test is required. Non-reproductive-aged women are defined as those who have been postmenopausal for at least 1 year, or have undergone surgical sterilization or hysterectomy；If there is a risk of conception, all subjects (regardless of male or female) should use contraceptive measures with an annual failure rate of less than 1% throughout the treatment period until 120 days (or 180 days after the last administration of the study drug) after the last administration of the study drug.

You may not qualify if:

• Concurrent participation in another interventional clinical study or receiving other investigational drugs, 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 treatment with Chinese patent medicines with anti-tumor indications or immunomodulatory drugs (including thymosin, interferon, and interleukins; except for local administration to control pleural effusion or ascites) within 2 weeks prior to first dose.
• Current use of oral or intravenous beta-blockers (e.g., atenolol, bisoprolol, carvedilol, labetalol, metoprolol, nadolol, sotalol, etc.) that cannot be safely switched to non-beta-blocker alternatives. Current subjects should have a washout period of at least 14 days with adequate transition period.
• Contraindications to Beta-Blocker Use Hypersensitivity to any component of this product Bronchial asthma or risk of bronchospasm Ketoacidosis and metabolic acidosis Severe or symptomatic bradycardia, atrioventricular block (Grade II or III), sinoatrial block, sick sinus syndrome Cardiogenic shock Right heart dysfunction caused by pulmonary hypertension Congestive heart failure (NYHA Class III or IV) Hypotension (systolic blood pressure \<100 mmHg) Prolonged fasting state Severe peripheral circulatory failure (e.g., gangrene) Symptomatic peripheral arterial disease or Raynaud's syndrome, untreated pheochromocytoma Unstable angina or Prinzmetal's angina Concurrent use of rizatriptan benzoate Severe chronic obstructive pulmonary disease (COPD) Uncontrolled Type I or Type II diabetes mellitus (glycated hemoglobin \[HbA1C\] \>8.5 or fasting glucose \>160 mg/dL at screening)
• Hepatic encephalopathy, hepatorenal syndrome, or Child-Pugh Class B or more severe cirrhosis.
• Malignant bowel obstruction (within 3 months prior to informed consent signing) or history of the following conditions: inflammatory bowel disease or extensive intestinal resection (partial colectomy or extensive small bowel resection with concurrent chronic diarrhea), Crohn's disease, or ulcerative colitis.
• Completion of palliative radiotherapy within 7 days prior to first study drug administration.
• Clinically active diverticulitis, intra-abdominal abscess, or gastrointestinal obstruction.
• History of psychoactive drug abuse or drug addiction.
• Known hypersensitivity to active ingredients or excipients of the study drug.
• Known history of primary immunodeficiency, or ongoing systemic corticosteroid therapy or any other form of immunosuppressive therapy.
• Use of immunosuppressive drugs within 4 weeks prior to first study treatment, excluding intranasal, inhaled, or other routes of topical corticosteroids, or physiological doses of systemic corticosteroids (i.e., not exceeding 10 mg/day prednisone or equivalent dose of other corticosteroids), or corticosteroids used for prevention of contrast agent allergy.
• Failure to recover adequately (i.e., to Grade ≤1 or baseline, excluding fatigue or alopecia) from any intervention-induced toxicities and/or complications prior to starting treatment.
• Receipt of live attenuated vaccines within 4 weeks prior to first study treatment or planned vaccination during the study (inactivated influenza vaccine for seasonal influenza is allowed within 4 weeks prior to first dose; however, live attenuated influenza vaccine is not permitted).

Sponsors & Collaborators

• Second Xiangya Hospital of Central South University: lead
• Shanghai Junshi Bioscience Co., Ltd.: collaborator

Study Sites (4)

The Second Xiangya Hospital of Central south University

Changsha, Hunan, China 410011, China

RECRUITING

Hunan Cancer Hospital

Changsha, Hunan, China

NOT YET RECRUITING

The Third Xiangya Hospital of Central South University

Changsha, Hunan, China

NOT YET RECRUITING

Xiangya Hospital, Central South University

Changsha, Hunan, China

NOT YET RECRUITING

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Interventions

Propranolol; toripalimab; Drug Therapy

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Phenoxypropanolamines; Propanolamines; Amino Alcohols; Alcohols; Organic Chemicals; Propanols; Amines; Naphthalenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Polycyclic Compounds; Therapeutics

Central Study Contacts

Fang Wu

CONTACT

+86 13574858332; wufang4461@csu.edu.cn

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Chief Physician, Professor, and Deputy Director of the Department of Oncology

Study Record Dates

• First Submitted: October 12, 2026
• First Posted: October 21, 2026
• Study Start: June 1, 2026
• Primary Completion (Estimated): December 31, 2028
• Study Completion (Estimated): December 31, 2029
• Last Updated: October 21, 2026

Record last verified: 2026-10

Data Sharing

• IPD Sharing: Will not share

Locations

CN (4)