Sintilimab Combined With Tafolecimab and Chemotherapy as First-Line Treatment for Extensive-Stage Small Cell Lung Cancer

Официальное название

Efficacy and Safety of Sintilimab Combined With Tafolecimab and Chemotherapy as First-Line Treatment for Extensive-Stage Small Cell Lung Cancer (STAR-SCLC)：A Prospective, Single Arm Trial

Обзор

This is a single arm, multi-center clinical trial. The goal of this clinical trial is to evaluate the efficacy, safety and biomarkers of Tafolecimab combined with Sintilimab and Chemotherapy as first-line treatment for patients with extensive-stage small cell lung cancer (ES-SCLC). Tafolecimab is a recombinant fully humanized monoclonal antibody against proprotein convertase subtilisin/kexin type 9 (PCSK-9), which can reduce low-density lipoprotein-C levels and increase the expression level of major histocompatibility complex class I (MHC-I) on tumor cells. Sintilimab is a fully humanized IgG4 monoclonal antibody targeting programmed cell death protein 1 (PD-1).

Подробное описание

Eligible patients will receive 4 cycles of Tafolecimab (300mg, sc, d1, Q3W) in combination with Sintilimab (200mg, iv, d1, Q3W), along with etoposide and either carboplatin (AUC 5 mg/mL/min) or cisplatin (75 mg/m2) administered intravenously on days 1, 2, and 3 of each 3-week cycle for up to 4 to 6 cycles. Subsequently, patients will receive maintenance therapy with Sintilimab and Tafolecimab until disease progression, the occurrence of intolerable toxicities, or the treatment duration reaches 2 years. If the investigator assesses potential evidence of clinical benefit, continuing treatment after disease progression is permitted.

PRIMARY OBJECTIVES:

I. To evaluate the progression-free survival (PFS) of Tafolecimab combined with Sintilimab and chemotherapy as first-line treatment regimens for patients with extensive-stage small cell lung cancer (ES-SCLC).

SECONDARY OBJECTIVES:

I. To evaluate the safety of of Tafolecimab combined with Sintilimab and chemotherapy as first-line treatment regimens for patients with ES-SCLC.

II. To evaluate the PFS rate, objective response rate (ORR), disease control rate (DCR), duration of response (DOR), overall survival (OS) rate and OS of Tafolecimab combined with Sintilimab and chemotherapy as first-line treatment regimens for patients with ES-SCLC.

TERTIARY OBJECTIVES:

I. To evaluate whether Tafolecimab combined with Sintilimab and chemotherapy as first-line treatment for patients with ES-SCLC could upregulate the expression of MHC-I on SCLC tumor cells.

II. To explore tissue and liquid biopsy biomarkers that may be predictive of response or primary resistance to Tafolecimab combined with Sintilimab and chemotherapy.

Вмешательства

• Препарат Tafolecimab
  Patients will receive Tafolecimab 300 mg every 3 weeks.
• Препарат Sintilimab (approved)
  Patients will receive Sintilimab 200 mg every 3 weeks.
• Препарат Etoposide
  Patients will recieve Etoposide (100 mg/m2) intravenously on days 1, 2, and 3 of each 3-week cycle.
• Препарат Carboplatin / Cisplatin
  Patients will receive carboplatin (AUC 5 mg/mL/min) or cisplatin (75 mg/m2) intravenously on day 1 of each 3-week cycle for up to 4 to 6 cycles.

Первичные конечные точки

• Progression-free Survival as Assessed by RECIST v1.1 [Срок оценки: From enrollment to the end of treatment at 12 months]

Вторичные конечные точки (7)

• Objective Response Rate as Assessed by RECIST v1.1 [Срок оценки: From enrollment to the end of treatment at 12 months]
• Progression-free Survival Rate as Assessed by RECISIT v1.1 [Срок оценки: From enrollment to the end of treatment at 6 months and 12 months]
• Overall Survival Rate as Assessed by RECISIT v1.1 [Срок оценки: From enrollment to the end of treatment at 12 months and 24 months]
• Disease Control Rate as Assessed by RECISIT v1.1 [Срок оценки: From enrollment to the end of treatment at 12 months]
• Duration of Response as Assessed by RECISIT v1.1 [Срок оценки: From enrollment to the end of treatment at 12 months]
• Percentage of Participants with Treatment-Related Adverse Events as Assessed by NCI-CTCAE v5.0 [Срок оценки: From enrollment to the end of treatment at 12 months]
• Overall survival as Assessed by RECISIT v1.1 [Срок оценки: From enrollment to the end of treatment at 24 months]

Критерии участия

Критерии включения

• Age ≥18 years, ECOG performance status 0-1;
• Histologically or cytologically confirmed extensive-stage small cell lung cancer (ES-SCLC) according to Veterans Administration Lung Study Group criteria;
• Previously not receiving systemic treatment for ES-SCLC;
• Greater than or equal to 1 measurable lesion exists according to RECIST v1.1;
• Expected survival >= 12 weeks;
• Adequate organ system functions (no blood transfusion or component blood use within 14 days before testing).

Критерии исключения

• Previously receiving systemic anti-tumor therapy for ES-SCLC;
• Combined SCLC (mixed SCLC and NSCLC histological types) or transformed SCLC confirmed by histological or cytological examination;
• Receiving other investigational drugs or participated in other interventional clinical studies within 4 weeks before signing the informed consent form;
• Receiving systemic immunostimulant treatment within 4 weeks before enrollment;
• Active central nervous system (CNS) metastases (asymptomatic patients with stable lesions allowed);
• Severe cardiovascular disease;
• Severe chronic/active infections requiring systemic antibacterial, antifungal or antiviral treatment within 2 weeks before enrollment;
• Active hepatitis B virus (HBV)/ hepatitis C virus (HCV)/ human immunodeficiency virus (HIV) infection;
• Active autoimmune diseases, a history of interstitial lung disease, or other uncontrolled systemic diseases;
• Pregnancy or lactation;
• Having a disease that requires systemic corticosteroids or other immunosuppressants to be treated within ≤14 days before enrollment;
• Requiring at least monthly or more frequent drainage of pleural and/or pericardial or peritoneal effusion;
• Using attenuated live vaccines, or planned to receive attenuated live vaccines within 28 days before enrollment;
• Known to be allergic to Sintilimab or Tafolecimab or its excipients, having a history of severe allergic reaction to any monoclonal antibody, or having a history of allergy to cisplatin, carboplatin or etoposide;
• Toxicity caused by previous anti-cancer treatment has not recovered to baseline or stable state at the time of enrollment;
• Creatinine clearance rate < 60 mL/min (cisplatin) or < 45 mL/min (carboplatin)
• Uncontrolled or symptomatic hypercalcemia.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Не применимо

Модель

Одна группа

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

Китай · 5 центров

• Hunan Cancer Hospital/the Affiliated Cancer Hospital of Xiangya School of Medicine, Centra — Чанша
• Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Aca — Цзинань
• Department of Thoracic Medical Oncology, Zhejiang Cancer Hospital, Hangzhou Institute of M — Ханчжоу
• First Affiliated Hospital, School of Medicine, Zhejiang University — Ханчжоу
• Second Affiliated Hospital, School of Medicine, Zhejiang University — Ханчжоу

Публикации

• Zugazagoitia J, Osma H, Baena J, Ucero AC, Paz-Ares L. Facts and Hopes on Cancer Immunotherapy for Small Cell Lung Cancer. Clin Cancer Res. 2024 Jul 15;30(14):2872-2883. doi: 10.1158/1078-0432.CCR-23-1159. PMID 38630789
• Mei W, Faraj Tabrizi S, Godina C, Lovisa AF, Isaksson K, Jernstrom H, Tavazoie SF. A commonly inherited human PCSK9 germline variant drives breast cancer metastasis via LRP1 receptor. Cell. 2025 Jan 23;188(2):371-389.e28. doi: 10.1016/j.cell.2024.11.009. Epub 2024 Dec 9. PMID 39657676
• Liu X, Bao X, Hu M, Chang H, Jiao M, Cheng J, Xie L, Huang Q, Li F, Li CY. Inhibition of PCSK9 potentiates immune checkpoint therapy for cancer. Nature. 2020 Dec;588(7839):693-698. doi: 10.1038/s41586-020-2911-7. Epub 2020 Nov 11. PMID 33177715
• Ma S, He Z, Liu Y, Wang L, Yang S, Wu Y, Chen H, Wu Y, Wang Q. Sintilimab plus anlotinib as second or further-line therapy for extensive disease small cell lung cancer: a phase 2 investigator-initiated non-randomized controlled trial. EClinicalMedicine. 2024 Mar 14;70:102543. doi: 10.1016/j.eclinm.2024.102543. eCollection 2024 Apr. PMID 38516099

Идентификаторы

NCT: NCT07061535 · 2025LSYD0847H

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

Открыть это исследование на ClinicalTrials.gov ↗