Propranolol Hydrochloride Combined With Adebrelimab and Platinum-Based Chemotherapy in Small Cell Lung Cancer

NCT07886047 | Recruiting Phase 1

• 1 other identifier: LYG20260075
• Study Type: interventional
• Target: 18
• Locations: 1 country
• Sites: 4

Brief Summary

This is a prospective multicenter, open-label, Phase I clinical study designed to evaluate the safety, tolerability, and preliminary efficacy of propranolol hydrochloride in combination with adebrelimab and platinum-based chemotherapy in patients with small cell lung cancer (SCLC).The study includes two cohorts: patients with previously untreated extensive-stage SCLC and patients with resectable early-stage (T1-2N0M0) SCLC. 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 SCLC.

Conditions

Small Cell Lung Cancer (SCLC)

Keywords

Small Cell Lung Cancer; Propranolol; Beta-Adrenergic Blockade; Adebrelimab; Immune Checkpoint Inhibitors

Outcome Measures

Primary Outcomes (5)

• Objective Response Rate (ORR) in the Extensive-Stage SCLC Cohort

  Objective response rate is defined as the proportion of participants with extensive-stage small cell lung cancer who achieve a best overall response of complete response (CR) or partial response (PR), as assessed by investigators according to Response Evaluation Criteria in Solid Tumors (RECIST), version 1.1.

  Through study completion, up to 24 months.

• Disease Control Rate (DCR) in the Extensive-Stage SCLC Cohort

  Disease control rate is defined as the proportion of participants with extensive-stage small cell lung cancer who achieve a best overall response of complete response (CR), partial response (PR), or stable disease (SD), as assessed by investigators according to RECIST version 1.1.

  Through study completion, up to 24 months.

• Incidence and Severity of Treatment-Emergent Adverse Events in the Extensive-Stage SCLC Cohort

  Safety will be evaluated by the number and percentage of participants experiencing treatment-emergent adverse events (TEAEs), including serious adverse events (SAEs) and immune-related adverse events (irAEs). Adverse events 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 24 months.

• R0 Resection Rate in the Resectable Early-Stage SCLC Cohort

  The R0 resection rate is defined as the proportion of participants scheduled for surgery who successfully undergo complete surgical resection with microscopically negative margins (R0) following neoadjuvant treatment with propranolol hydrochloride, adebrelimab, and platinum-based chemotherapy.

  Perioperative

• Incidence and Severity of Treatment-Related Adverse Events and Perioperative Complications in the Resectable Early-Stage SCLC Cohort

  The incidence and severity of treatment-related adverse events and perioperative complications will be assessed in participants with resectable early-stage small cell lung cancer (SCLC). Safety during neoadjuvant therapy will be evaluated based on adverse events (AEs), serious adverse events (SAEs), and immune-related adverse events (irAEs), with severity graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE), version 5.0. Perioperative complications will be assessed based on the occurrence and severity of intraoperative and postoperative complications, including perioperative mortality.

  Through study completion, up to 12 months.

Secondary Outcomes (7)

• Progression-Free Survival (PFS) in the Extensive-Stage SCLC Cohort

  Through study completion, up to 24 months.

• Overall Survival (OS)

  Through study completion, up to 24 months.

• Pathological Complete Response (pCR) Rate in the Resectable Early-Stage SCLC Cohort

  Perioperative

• Major Pathological Response (MPR) Rate in the Resectable Early-Stage SCLC Cohort

  Perioperative

• Disease-Free Survival (DFS) in the Resectable Early-Stage SCLC Cohort

  Through study completion, up to 12 months.

Study Arms (2)

Extensive-Stage SCLC Cohort

EXPERIMENTAL

Patients with previously untreated extensive-stage small cell lung cancer (ES-SCLC) will receive oral propranolol hydrochloride at escalating dose levels (10 mg BID, 10 mg TID, and 20 mg BID) using a 3+3 design, in combination with adebrelimab and platinum-based chemotherapy every 3 weeks for 4-6 cycles. This will be followed by maintenance treatment with propranolol hydrochloride and adebrelimab for up to 2 years or until disease progression, unacceptable toxicity, or other protocol-defined discontinuation criteria are met. Safety, tolerability, dose-limiting toxicities, and the recommended Phase II dose will be evaluated.

Drug: Propranolol Hydrochloride; Drug: Adebrelimab; Drug: Chemotherapy

Resectable Early-Stage (T1-2N0M0) SCLC Cohort

EXPERIMENTAL

Patients with resectable early-stage (T1-2N0M0) SCLC will receive neoadjuvant propranolol hydrochloride at escalating dose levels (10 mg BID, 10 mg TID, and 20 mg BID) using a 3+3 dose-escalation design, in combination with adebrelimab and platinum-based chemotherapy every 3 weeks for 3-4 cycles, followed by surgical resection. Postoperatively, patients will continue treatment with propranolol hydrochloride and adebrelimab for up to 1 year. Safety, tolerability, dose-limiting toxicities, surgical feasibility, and pathological response will be evaluated.

Drug: Propranolol Hydrochloride; Drug: Adebrelimab; Drug: Chemotherapy

Interventions

Chemotherapy DRUG

Platinum-based doublet chemotherapy consists of etoposide plus either carboplatin or cisplatin. Etoposide: 100 mg/m² intravenously on Days 1-3 of each 21-day cycle. Carboplatin: AUC 5 intravenously on Day 1 of each 21-day cycle; or Cisplatin: 75 mg/m² intravenously on Day 1 of each 21-day cycle.

Extensive-Stage SCLC Cohort; Resectable Early-Stage (T1-2N0M0) SCLC Cohort

Propranolol Hydrochloride DRUG

Propranolol hydrochloride is administered orally at three planned dose levels: 10 mg twice daily (BID), 10 mg three times daily (TID), and 20 mg twice daily (BID). Dose escalation follows a conventional 3+3 design in both study cohorts to evaluate safety, dose-limiting toxicities, and the recommended Phase II dose (RP2D).

Also known as: Inderal

Extensive-Stage SCLC Cohort; Resectable Early-Stage (T1-2N0M0) SCLC Cohort

Adebrelimab DRUG

Adebrelimab is administered intravenously at a dose of 1200 mg on Day 1 of each 21-day cycle in combination with propranolol hydrochloride and platinum-etoposide chemotherapy. In the extensive-stage SCLC cohort, adebrelimab is continued as maintenance therapy for up to 2 years. In the resectable early-stage SCLC cohort, adebrelimab is administered as neoadjuvant treatment followed by postoperative therapy for up to 1 year, according to the study protocol.

Extensive-Stage SCLC Cohort; Resectable Early-Stage (T1-2N0M0) SCLC Cohort

Eligibility Criteria

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

You may qualify if:

• Written informed consent must be obtained prior to any study-related procedures
• Age ≥18 years and ≤75 years.
• Eastern Cooperative Oncology Group (ECOG) performance status score of 0-1
• Life expectancy ≥12 weeks.
• Histologically or cytologically confirmed extensive-stage (ES) SCLC or T1-2N0M0 stage SCLC patients(9th UICC/AJCC TNM staging). Extensive-stage patients not amenable to local therapy include both recurrent and treatment-naïve patients not suitable for local treatment (surgery and definitive concurrent chemoradiotherapy), who have not previously received systemic therapy for advanced/metastatic disease.
• At least one measurable lesion according to Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1. Lesions located within prior radiation fields may be considered measurable if progression has been documented (within 28 days prior to first treatment).
• Asymptomatic or symptomatic brain metastases that have been locally treated and are stable are allowed in ES-SCLC cohort, provided the subject meets the following conditions: Measurable disease outside the central nervous system (CNS) No CNS symptoms, or symptoms stable for at least 2 weeks No corticosteroid treatment required, or corticosteroids discontinued at least 7 days prior to first dose, or stable corticosteroid dose at ≤10 mg/day prednisone (or equivalent) for at least 7 days prior to first dose
• Laboratory Parameters (within 14 days prior to first treatment) Hematologic: Absolute neutrophil count (ANC) ≥1.5×10⁹/L; platelet count ≥100×10⁹/L; hemoglobin ≥9.0 g/dL (without transfusion or erythropoietin administration within 7 days). Hepatic: Total bilirubin (TBIL) ≤1.5×upper limit of normal (ULN); alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤2.5×ULN (in absence of hepatic metastases). For patients with hepatic metastases: ALT or AST ≤5×ULN. Renal: Serum creatinine (Cr) ≤1.5×ULN or creatinine clearance ≥60 mL/min (by Cockcroft-Gault formula), and urinalysis showing urine protein (UPRO) \<2+ or 24-hour urine protein \<1 g. Coagulation: Within 7 days prior to study treatment: International normalized ratio (INR) ≤1.5×ULN or prothrombin time (PT) ≤1.5×ULN; if subject is receiving anticoagulant therapy, PT within the intended therapeutic range of the anticoagulant is acceptable.
• New York Heart Association (NYHA) Class \<3; left ventricular ejection fraction (LVEF) ≥50%; baseline electrocardiogram (ECG) showing no PR interval prolongation or atrioventricular block.
• For women of childbearing potential (WOCBP), a negative urine or serum pregnancy test must be obtained within 3 days prior to first study drug administration (Cycle 1 Day 1). If urine pregnancy test results cannot be confirmed as negative, a serum pregnancy test is required. Non-childbearing potential is defined as postmenopausal for at least 1 year, or surgically sterile (bilateral oophorectomy, hysterectomy, or tubal ligation). All subjects (male and female) with reproductive potential must use highly effective contraception (failure rate \<1% per year) throughout the treatment period and for 120 days (or 180 days) after the last dose of 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 Shengdi Pharmaceutical Co., Ltd: collaborator

Study Sites (4)

The Second Xiangya Hospital of Central south University

Changsha, Hunan, 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

Small Cell Lung Carcinoma

Interventions

Propranolol; 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, MD, PhD

CONTACT

+86-13574858332; wufang4461@csu.edu.cn

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor, Chief Physician, and Deputy Department Director

Model Details: This study includes two parallel, non-randomized cohorts: patients with extensive-stage small cell lung cancer and patients with resectable early-stage (T1-2N0M0) small cell lung cancer. Both cohorts are conducted concurrently and undergo protocol-defined dose escalation. The cohorts are evaluated separately and are not intended for direct comparative analysis.

Study Record Dates

• First Submitted: October 11, 2026
• First Posted: October 21, 2026
• Study Start: May 29, 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)