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

NCT ID: NCT07061535

Last Updated: 2025-07-11

Basic Information

• Recruitment Status: NOT_YET_RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 40 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2025-08-01
• Study Completion Date: 2027-08-01

Brief Summary

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).

Detailed Description

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.

Conditions

Extensive-stage Small Cell Lung Cancer (ES-SCLC); Extensive Stage Lung Small Cell Cancer; Extensive-Stage Small-Cell Lung Cancer; Extensive Disease Small Cell Lung Cancer

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Tafolecimab + Sintilimab + Chemotherapy

Eligible patients will receive 4 cycles of Tafolecimab (300 mg, sc, d1, Q3W) in combination with Sintilimab (200 mg, iv, d1, Q3W), along with etoposide and either carboplatin (AUC 5 mg/mL/min) or cisplatin (75 mg/m2) for up to 4 to 6 cycles. Subsequently, they will receive maintenance therapy with Sintilimab and Tafolecimab until disease progression, the occurrence of intolerable toxicities, or the completion of 2 years of treatment. Etoposide (100 mg/m2) will be administered intravenously on days 1, 2, and 3 of each 3-week cycle, while carboplatin or cisplatin will be given intravenously on day 1 of each 3-week cycle.

Group Type: EXPERIMENTAL

Tafolecimab

Intervention Type: DRUG

Patients will receive Tafolecimab 300 mg every 3 weeks.

Sintilimab (approved)

Intervention Type: DRUG

Patients will receive Sintilimab 200 mg every 3 weeks.

Etoposide

Intervention Type: DRUG

Patients will recieve Etoposide (100 mg/m2) intravenously on days 1, 2, and 3 of each 3-week cycle.

Carboplatin / Cisplatin

Intervention Type: DRUG

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.

Interventions

Tafolecimab

Patients will receive Tafolecimab 300 mg every 3 weeks.

Intervention Type: DRUG

Sintilimab (approved)

Patients will receive Sintilimab 200 mg every 3 weeks.

Intervention Type: DRUG

Etoposide

Patients will recieve Etoposide (100 mg/m2) intravenously on days 1, 2, and 3 of each 3-week cycle.

Intervention Type: DRUG

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.

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• 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).

Exclusion Criteria

• 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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Innovent Biologics, Inc.

OTHER

Sponsor Role: collaborator

Second Affiliated Hospital, School of Medicine, Zhejiang University

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

Hunan Cancer Hospital/the Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University

Changsha, Hunan, China

Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Science

Jinan, Shandong, China

Department of Thoracic Medical Oncology, Zhejiang Cancer Hospital, Hangzhou Institute of Medicine (HIM), Chinese Academy of Sciences

Hangzhou, Zhejiang, China

First Affiliated Hospital, School of Medicine, Zhejiang University

Hangzhou, Zhejiang, China

Second Affiliated Hospital, School of Medicine, Zhejiang University

Hangzhou, Zhejiang, China

Countries

China

Central Contacts

Yang Xia, MD, PhD

Role: CONTACT

yxia@zju.edu.cn

+8618868439669

Facility Contacts

Yongchang Zhang, MD, PhD

Role: primary

zhangyongchang@csu.edu.cn

+8613873123436

Xiangjiao Meng, MD, PhD

Role: primary

mengxiangjiao@sina.com

+8613793150996

Jing Qin, MD, PhD

Role: primary

qinjing@zjcc.org.cn

Jian Ruan, MD, PhD

Role: primary

software233@zju.edu.cn

Yang Xia, MD, PhD

Role: primary

yxia@zju.edu.cn

+8618868439669

References

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.

Reference Type: BACKGROUND

PMID: 38630789 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 39657676 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 33177715 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 38516099 (View on PubMed)

Other Identifiers

2025LSYD0847H

Identifier Type: -

Identifier Source: org_study_id