Overview
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).
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.
Eligibility
Key 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).
Key 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.
