Adebrelimab Maintenance Therapy After Concurrent Chemoradiotherapy with Hyperfractionated Radiotherapy in Limited-Stage Small Cell Lung Cancer

NCT06784206 | Not Yet Recruiting Phase 2

• 1 other identifier: 2024YJZ163
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

Brief Summary

Small cell lung cancer (SCLC) remains a challenging disease with poor prognosis and limited treatment options despite decades of research. SCLC is an immunogenic tumor, and the use of T-cell immune checkpoint inhibitors targeting the PD-1/PD-L1 axis has shown promising antitumor activity, potentially extending patient survival. The combination of concurrent chemoradiotherapy followed by immune maintenance therapy has demonstrated significant efficacy in limited-stage SCLC. Moreover, hyperfractionated accelerated radiotherapy (HART) has been shown to improve overall survival in limited-stage SCLC compared to standard dose radiotherapy without increasing toxicity. However, there is a lack of exploration into the use of immune checkpoint inhibitors following concurrent chemoradiotherapy with HART in limited-stage SCLC. This exploratory clinical study aims to investigate the efficacy and safety of adebrelimab maintenance treatment following concurrent chemoradiotherapy with HART in patients with limited-stage SCLC through a single-arm, open-label, prospective, single-center clinical trial.

Conditions

Small Cell Lung Cancer, Limited Stage; Hyperfractionated Accelerated Radiotherapy; Simultaneous Radiotherapy and Chemotherapy

Outcome Measures

Primary Outcomes (1)

• Treatment-related adverse events

  Treatment-related adverse events according to CTCAE 5.0

  Duration of treatment and follow up until death or 90 days after enrollment

Secondary Outcomes (4)

• PFS

  From enrollment to the end of treatment at 1 and 2 year

• OS

  From date of enrollment to maximum of 2 years or death

• ORR

  From date of enrollment to maximum of 2 years

• DCR

  From date of enrollment to maximum of 2 years

Study Arms (1)

experimental group

EXPERIMENTAL

In this study, patients will receive concurrent hyperfractionated accelerated radiotherapy (HART) combined with chemotherapy for 4 cycles. If patients achieve a complete response (CR) or partial response (PR) after the initial treatment, they will be given prophylactic cranial irradiation (PCI). Following PCI, patients will enter the maintenance treatment phase with Adebrelimab, which will continue until disease progression, death, or the development of intolerable toxicity.

Drug: Adebrelimab Maintenance Therapy After Concurrent Chemoradiotherapy with Hyperfractionated Radiotherapy

Interventions

Adebrelimab Maintenance Therapy After Concurrent Chemoradiotherapy with Hyperfractionated Radiotherapy DRUG

Chemotherapy: Etoposide will be administered intravenously at a dose of 100 mg/m² on days 1 to 3 of each cycle. Cisplatin will be given at a dose of 75 mg/m² on day 1 of each cycle. The treatment will be repeated every 3 weeks for a total of 4 cycles. Concurrent Radiotherapy: Chest radiotherapy will be initiated concurrently with the first 3 cycles of chemotherapy. The total dose of radiotherapy will be 54 Gy, delivered in 30 fractions, with 2 fractions per day. Prophylactic Cranial Irradiation (PCI): For patients who achieve a partial response (PR) or complete response (CR) after chemoradiotherapy, PCI will be administered 3 to 4 weeks after the completion of chemoradiotherapy. The dose for PCI will be 25 Gy in 10 fractions. Adebrelimab Maintenance Therapy: Following PCI, patients will receive maintenance therapy with Adebrelimab. The dose will be 1200 mg administered intravenously on day 1 of each cycle. The treatment will be repeated every 3 weeks until disease progression, death

experimental group

Eligibility Criteria

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

You may qualify if:

• Age: 18-75 years, both genders are eligible;
• Histologically or cytologically confirmed limited-stage small cell lung cancer (according to the 8th edition of AJCC staging);
• Patients who have previously received no more than 2 cycles of standard chemotherapy or are treatment-naive;
• ECOG performance status: 0-1;
• Presence of measurable lesions according to RECIST 1.1 criteria (for RECIST 1.1 criteria, the longest diameter of tumor lesions on CT scan ≥10mm, and the shortest diameter of lymph node lesions on CT scan ≥15mm);
• Estimated life expectancy of at least three months;
• Participants must have adequate pulmonary function;
• Normal function of major organs, which means meeting the following criteria:
• Complete blood count:
• Hemoglobin (HGB) ≥90 g/L; Absolute neutrophil count (ANC) ≥1.5×10⁹/L; Platelet count (PLT) ≥100×10⁹/L; White blood cell count (WBC) ≥3.0×10⁹/L;
• Biochemical tests:
• Serum albumin (ALB) ≥30 g/L; Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) \<3×ULN; Total bilirubin (TBIL) ≤1.5×ULN; this does not apply to patients diagnosed with Gilbert's syndrome (persistent or recurrent hyperbilirubinemia \[mainly unconjugated bilirubin\], without evidence of hemolysis or liver pathology). After consultation with a physician, patients with this condition may be allowed to participate in the study.
• Creatinine ≤1.5×ULN;
• Women of childbearing potential must have taken reliable contraceptive measures or have had a negative pregnancy test (serum or urine) within 7 days before enrollment. Both men and women of childbearing age must agree to take adequate contraceptive measures throughout the study period and for 6 months after the end of treatment;
• Participants voluntarily join this study, sign the informed consent form, have good compliance, and cooperate with follow-ups.

You may not qualify if:

• Histological mixture of SCLC and NSCLC components;
• Extensive-stage SCLC;
• Patients with a history of allogeneic organ transplant or allogeneic hematopoietic stem cell transplant or planned for transplant;
• Use of immunosuppressive drugs (including but not limited to prednisone, cyclophosphamide, azathioprine, methotrexate, thalidomide, and anti-tumor necrosis factor drugs) within 14 days before the first use of Adebrelimab, excluding nasal and inhaled corticosteroids or physiologic doses of systemic corticosteroids (i.e., no more than 10 mg/day of prednisolone or equivalent physiologic dose of other corticosteroids);
• Known allergy to etoposide, cisplatin, Adebrelimab, or drug excipients; or severe allergic reactions to other monoclonal antibodies; Vaccination with live attenuated vaccines within 4 weeks before the first dose or planned during the study period;
• Presence of any active autoimmune disease or history of autoimmune disease (including but not limited to: autoimmune hepatitis, interstitial pneumonia, uveitis, enteritis, hypophysitis, vasculitis, nephritis, hyperthyroidism, hypothyroidism) is not eligible. Exceptions to this criterion include:
• Patients with vitiligo or alopecia;
• Patients with stable hypothyroidism under hormone replacement therapy (e.g., after Hashimoto's syndrome);
• Participants undergoing systemic treatment with bronchodilators, with unsatisfactory asthma control, are not eligible (those who had complete remission of asthma in childhood and require no intervention in adulthood may be included);
• Urinalysis showing proteinuria ≥++, or confirmed 24-hour urine protein ≥1.0g;
• Previously diagnosed with any other malignancy, except for the following conditions:
• Adequately treated basal cell or squamous cell carcinoma of the skin or carcinoma in situ of the cervix;
• Malignancies treated with curative intent, with no known active disease for ≥5 years before the first dose in the study and with a low potential risk of recurrence;
• Infection with human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome (AIDS);
• Within 6 months before enrollment, occurrence of the following conditions: myocardial infarction, severe/unstable angina, NYHA class 2 or higher heart failure, poorly controlled arrhythmias (including QTcF interval \>450 ms for males, \>470 ms for females, QTcF interval calculated by Fridericia formula), symptomatic congestive heart failure;

Sponsors & Collaborators

• Peking University Cancer Hospital & Institute: lead

Study Sites (1)

Peking University Cancer Hospital and Institute

Beijing, Beijing Municipality, 100142, China

Location

MeSH Terms

Conditions

Small Cell Lung Carcinoma

Condition Hierarchy (Ancestors)

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

Central Study Contacts

AnHui Shi, MD

CONTACT

139 0113 6511; anhuidoctor@163.com

JiaYi Yu, MD

CONTACT

18518362213; yujiayi0323@foxmail.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Chief Physician

Study Record Dates

• First Submitted: January 14, 2025
• First Posted: January 20, 2025
• Study Start: February 1, 2025
• Primary Completion: August 1, 2026
• Study Completion (Estimated): January 1, 2028
• Last Updated: January 20, 2025

Record last verified: 2025-01

Data Sharing

• IPD Sharing: Will share

Locations

CN (1)