Serplulimab Combined With CCRT for LS-SCLC.

A Single-arm Phase II Clinical Trial of Serplulimab Combined With Concurrent Chemoradiotherapy for Limited-stage Small Cell Lung Cancer(LS-SCLC).

Small cell lung cancer(SCLC) has a poor prognosis and a relatively short overall survival time, urgently requiring innovative treatment strategies to improve the prognosis of such patients. Immunotherapy has become an important component of first-line therapy for extensive-stage small cell lung cancer (ES-SCLC). Studies have found that, compared to chemotherapy alone, the combination of Surlidumab with carboplatin and etoposide can extend the median overall survival in ES-SCLC to over 15 months. However, to date, research on the use of immunotherapy in combination with concurrent chemoradiotherapy (CCRT) in limited-stage small cell lung cancer (LS-SCLC) remains limited. This study aims to explore the clinical benefits of Surlidumab in combination with concurrent chemoradiotherapy in LS-SCLC and evaluate the safety of immunotherapy in combination with CCRT as first-line treatment for LS-SCLC. At the same time, it seeks to identify tumor-related biomarkers that can effectively predict the efficacy of immunotherapy and prognosis.

Study Overview

• Status: Not yet recruiting
• Conditions: Small Cell Lung Cancer
• Intervention / Treatment: Drug: Serplulimab

Detailed Description

The study plans to include a total of 96 patients who will receive first-line treatment consisting of 4 cycles of etoposide plus cisplatin/carboplatin and concurrent thoracic radiotherapy combined with Surlidumab immunotherapy. Following CCRT+Surlidumab treatment, patients will undergo Surlidumab consolidation therapy until disease progression or for a duration of at least 1 year. The study aims to evaluate the progression-free survival (PFS) and overall survival (OS) of patients compared to those receiving concurrent chemoradiotherapy alone, and to explore the efficacy of immunotherapy in limited-stage small cell lung cancer. Additionally, peripheral blood samples will be collected before treatment and 1 month after CCRT to explore tumor efficacy-related biomarkers.

• Study Type: Interventional
• Enrollment (Estimated): 96
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Yan Xu, MD; Phone Number: +8618500296828; Email: maraxu@163.com
• Study Contact Backup: Name: mengzhao Wang, MD; Phone Number: +861311235467; Email: mengzhaowang@sina.com

Study Locations

• China
  • Beijing
    • Beijing, Beijing, China, 100730
      • Department of Respiratory and Critical Care Medicine, Peking Union Medical College Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Aged 18 years or older
2. Diagnosed with small cell lung cancer by histology or cytology, and staged as limited stage (stage II-III according to the 8th edition of AJCC Cancer Staging)
3. Treatment-naïve population, not having received any prior targeted therapy, chemotherapy, radiation therapy, or immunotherapy for anti-tumor treatment
4. Measurable lesions based on RECIST 1.1
5. Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1. ECOG assessment should be conducted within 7 days prior to the first dose of the study intervention
6. Baseline hematologic, blood biochemistry, and urine biochemistry tests confirming sufficient bone marrow and organ function
7. Life expectancy of at least 6 months
8. Male participants: Male participants must agree to use effective contraception during the study treatment and for at least 180 days after the last dose, and must not donate sperm during this period

9. Female participants must not be pregnant or lactating, and must meet at least one of the following conditions:

   1. Women who are not capable of reproduction or
   2. Agree to use effective contraception during the treatment and for at least 180 days after the last dose
   3. Women capable of reproduction must undergo a serum or urine pregnancy test within 72 hours before starting the medication, and the result must be negative (minimum sensitivity 25 IU/L or equivalent units of HCG)

(11) Signed informed consent form

Exclusion Criteria:

1. Patients with extensive-stage small cell lung cancer
2. Cancer patients who have undergone surgery, radiotherapy, chemotherapy, or immunotherapy for small cell lung cancer
3. LS-SCLC patients with stage I disease amenable to surgical resection
4. Patients with active autoimmune diseases requiring systemic treatment (with disease-modifying agents, corticosteroids, or immunosuppressive drugs) within the past 2 years. Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency) is allowed
5. History of (non-infectious) pneumonia/interstitial lung disease requiring steroids or current active pneumonia/interstitial lung disease requiring steroids
6. Previously diagnosed with immunodeficiency diseases such as immunoglobulin deficiency, aplastic anemia, etc.
7. Known history of human immunodeficiency virus (HIV) infection
8. Concurrent active hepatitis B (defined as HBV DNA > 500 copies) and hepatitis C virus (defined as HCV RNA (+)) infection
9. Known active tuberculosis history (tuberculin bacillus)
10. Receipt of live vaccine or attenuated live vaccine within 30 days prior to the first study intervention. Use of inactivated vaccines is allowed. Live vaccines include, but are not limited to: measles, mumps, rubella, varicella/zoster (chickenpox), yellow fever, rabies, Bacillus Calmette-Guérin (BCG), and typhoid vaccines. Injectable seasonal influenza vaccine is generally an inactivated virus vaccine and is allowed; however, intranasal influenza vaccine (e.g., FluMist®) is an attenuated live vaccine and is not allowed
11. Known other malignancy within the past 1 year that is progressing or requires active treatment. Note: Excludes adequately treated basal cell carcinoma, squamous cell skin cancer, or in situ carcinoma (excluding in situ bladder carcinoma)
12. Symptomatic central nervous system metastases and/or carcinomatous meningitis
13. Severe hypersensitivity reaction (≥3 grade) to nivolumab/platinum/etoposide and/or any of their excipients
14. Active infection requiring systemic therapy
15. Any medical condition the investigator believes would pose excessive risk to the patient. For example, poorly controlled diabetes, active infection requiring parenteral anti-infective therapy, hepatic failure, any psychiatric condition that would interfere with understanding the informed consent form (ICF). Any past or present disease, treatment, laboratory abnormality, or other condition that, in the opinion of the investigator, would confound the study results or interfere with participation throughout the study
16. Known psychiatric illness or substance abuse that would interfere with compliance with trial requirements
17. Pregnancy, lactation, planned pregnancy, or intent to become pregnant or father children during the expected duration of the study (from screening visit through 180 days after the last dose of investigational drug)
18. Prior allogeneic tissue/organ transplantation
19. Patients unable to comply with study visits
20. Currently participating in or has used other investigational drugs or devices

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Study arm; Concurrent radiotherapy with chemotherapy (Etoposide+Cisplatin/Carboplatin) with Serplulimab, and followed by consolidation Serplulimab	Drug: Serplulimab; Undergo 4 cycles of synchronous radiotherapy and chemotherapy combined with Sintilimab immunotherapy, followed by Sintilimab monotherapy for maintenance treatment until disease progression or up to 1 year.; Other Names: Cisplatin; Carboplatin; Etoposide; Concurrent radiotherapy Maintenance therapy

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression free survival	the time length from enrollment to any of the following events: disease progression with first line therapy or death from any cause. Disease progression will be assessed according to RECIST 1.1	up to 8 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of adverse events graded according to National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) version 5.0	Evaluate adverse events of any cause, treatment-related adverse events, immune-mediated adverse events according to NCI-CTCAE V5.0	up to 8 weeks
objective response rate (ORR)	Proportion of patients with Complete and Partial Responses to first-line therapy.	up to 8 weeks
Overall survival	the time length from enrollment to death from any cause.	up to 8 weeks

Collaborators and Investigators

• Sponsor: Peking Union Medical College Hospital
• Investigators: Principal Investigator: Mengzhao Wang, MD, Peking Union Medical College Hospital

Study record dates

Study Major Dates

• Study Start (Estimated): February 25, 2024
• Primary Completion (Estimated): January 25, 2027
• Study Completion (Estimated): December 31, 2027

Study Registration Dates

• First Submitted: January 27, 2024
• First Submitted That Met QC Criteria: February 28, 2024
• First Posted (Estimated): March 6, 2024

Study Record Updates

• Last Update Posted (Estimated): March 6, 2024
• Last Update Submitted That Met QC Criteria: February 28, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Neoplasms; Lung Diseases; Neoplasms by Site; Respiratory Tract Neoplasms; Thoracic Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Small Cell Lung Carcinoma; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Antineoplastic Agents, Phytogenic; Topoisomerase II Inhibitors; Topoisomerase Inhibitors; Carboplatin; Etoposide; Cisplatin
• Other Study ID Numbers: K5236

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No