Extensive Small Cell Lung Cancer
Conditions
Keywords
QL1706, Extensive Small Cell Lung Cancer, combination therapy, first line therapy
Brief summary
This single-arm, open-label, Phase II study assesses first-line QL1706 + bevacizumab (anti-VEGF) + platinum/etoposide chemotherapy to treat naïve ES-SCLC patients.The main questions it aims to answer are: Evaluate efficacy and safety of this quadruplet regimen in ES-SCLC Explore correlations between tumor biomarkers and treatment efficacy Participants will: Histologically or cytologically confirmed, treatment-naïve extensive-stage small cell lung cancer (ES-SCLC). Willing to provide archived or fresh tumor tissue samples. If unavailable, enrollment may proceed per investigator assessment. At least one measurable lesion per RECIST v1.1
Detailed description
Small cell lung cancer (SCLC) is a highly aggressive malignancy, accounting for 13-15% of all lung cancers. Approximately two-thirds of patients present with distant metastases at diagnosis, defined as extensive-stage SCLC (ES-SCLC). Prognosis remains poor, with median overall survival (mOS) of 12-15 months despite standard first-line chemotherapy using etoposide plus cisplatin/carboplatin (EP/EC), which offers limited benefit (mOS \ 10 months; median progression-free survival \[mPFS\] \ 5 months). Immune checkpoint inhibitors (ICIs) have improved outcomes modestly. IMpower133, KEYNOTE-604, RATIONALE-312, and EXTENTORCH trials confirmed the benefit of adding PD-1/PD-L1 inhibitors to chemotherapy, but the survival plateau remains. Dual immune checkpoint blockade strategies, including PD-1/PD-L1 with CTLA-4 inhibitors, have not significantly improved outcomes and pose higher toxicity, as seen in CASPIAN and CheckMate451 studies. Antiangiogenic therapy offers another promising direction. Studies such as SALUTE, ACTION-2, and BEAT-SC have explored bevacizumab or anlotinib combined with chemo-immunotherapy, showing potential survival gains. Notably, the ETER701 study using a four-drug combination achieved mOS of 19.3 months, although with increased adverse events. QL1706 (Aito combination antibody) is a novel bifunctional antibody targeting PD-1 and CTLA-4 in a 2:1 fixed ratio, designed to optimize synergy while reducing CTLA-4 toxicity. Approved in 2024, it has demonstrated efficacy and tolerability in multiple solid tumors. In NSCLC, QL1706 combined with chemotherapy and antiangiogenic therapy showed mPFS up to 8.5 months and mOS of 26.5 months. To date, no clinical data exist for QL1706 combined with antiangiogenic therapy and chemotherapy in ES-SCLC. A phase II, open-label, single-arm clinical trial is proposed to evaluate its efficacy and safety as first-line treatment. This study aims to explore a new therapeutic strategy to overcome the current survival limitations in ES-SCLC.
Interventions
DRUGQL1706 , bevacizumab, etoposide , cisplatin or carboplatin
Participants will receive QL1706 (5 mg/kg, IV, day 1), bevacizumab (7.5 mg/kg, IV, day 1), etoposide (100 mg/m², IV, days 1-3), plus either cisplatin (75 mg/m² split over days 1-2, IV) or carboplatin (AUC=5, IV, day 1) every 21 days for 4-6 cycles. Dose adjustments may be made based on clinical judgment. Patients who do not experience disease progression or intolerable toxicity will proceed to maintenance therapy with QL1706 (5 mg/kg, IV, day 1) and bevacizumab (7.5 mg/kg, IV, day 1) every 21 days, continued until disease progression, unacceptable toxicity, consent withdrawal, investigator decision, loss to follow-up, death, or other protocol-defined criteria. All participants will receive dual-agent maintenance therapy.
Sponsors
Peking University Cancer Hospital & Institute
Hebei Medical University Fourth Hospital
Tianjin Medical University Cancer Institute and Hospital
Renmin Hospital of Wuhan University
Wuhan TongJi Hospital
Peking University People's Hospital
Shanxi Province Cancer Hospital
Zhijie Wang
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Participants must meet all of the following criteria to be eligible for the study: 1. Signed written informed consent and willingness to comply with study procedures. 2. Age ≥18 years. 3. Estimated life expectancy ≥3 months. 4. ECOG performance status of 0 or 1. 5. Histologically or cytologically confirmed, treatment-naïve extensive-stage small cell lung cancer (ES-SCLC). 6. Willing to provide archived or fresh tumor tissue samples. If unavailable, enrollment may proceed per investigator assessment. 7. At least one measurable lesion per RECIST v1.1. 8. Fully understands and voluntarily participates in the study. 9. Adequate organ function as defined below: * Absolute neutrophil count ≥1.5 × 10⁹/L * Platelets ≥100 × 10⁹/L * Hemoglobin ≥90 g/L (without transfusion in prior 14 days) * Serum creatinine ≤1× ULN or creatinine clearance \>50 mL/min (Cockcroft-Gault) * AST and ALT ≤2.5× ULN (≤5× ULN with liver metastases) * Total bilirubin ≤1.5× ULN (except Gilbert's syndrome \<51.3 µmol/L) * TSH, FT3, FT4 within ±10% of normal limits
Exclusion criteria
1. Prior chemotherapy, immunotherapy, targeted therapy, or radiotherapy. 2. Histologic or cytologic evidence of non-small cell or mixed small cell/non-small cell carcinoma. 3. Symptomatic brain metastases or leptomeningeal disease. 4. Active or suspected autoimmune disease, except for stable vitiligo, type 1 diabetes, hypothyroidism requiring only hormone replacement, or conditions not expected to recur. 5. Evidence or history of active pulmonary tuberculosis (TB), including treated TB within the past year. 6. Concomitant condition requiring systemic corticosteroids or other immunosuppressive therapy. 7. Pregnant or breastfeeding females. 8. Symptomatic interstitial lung disease or suspected drug-related pneumonitis. 9. Positive for HIV antibodies, active HBV (HBsAg+ with HBV DNA \>10³ copies/mL), or active HCV infection (HCV-Ab+ with detectable RNA). 10. History of significant neurological or psychiatric disorders (e.g., dementia, depression, epilepsy, bipolar disorder). 11. Participation in another investigational drug study within 4 weeks prior to randomization. 12. Use of anti-tumor traditional Chinese medicine within 2 weeks prior to first study dose. 13. History of other malignancies within 2 years, except for cured non-melanoma skin cancers or certain in situ carcinomas. 14. Clinically significant cardiovascular or cerebrovascular disease (e.g., NYHA class ≥2 heart failure, recent myocardial infarction or stroke within 6 months). 15. History of thromboembolic events (e.g., DVT, PE, arterial thrombosis) within 6 months, except catheter-related thrombosis. 16. Live vaccination within 28 days before randomization or planned during the study. 17. Major surgery or significant trauma within 4 weeks prior to treatment initiation. 18. Conditions affecting drug absorption (e.g., severe vomiting, GI obstruction, active GI bleeding or perforation). 19. Active, uncontrolled bacterial, viral, or fungal infections despite appropriate treatment. 20. Known hypersensitivity to any study drug or excipients. 21. Any other condition deemed unsuitable by the investigator due to safety or compliance concerns.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Progression-Free Survival (PFS) | From enrollment to the end of monitoring at 2 years. | PFS is defined as the time from the first dose of study treatment to the first documentation of disease progression according to RECIST v1.1 (as assessed by investigators) or death from any cause, whichever occurs first. Subjects who are alive without progression at the time of analysis will be censored at the date of the last tumor assessment. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Overall Survival (OS) | From enrollment to the end of monitoring at 2 years. | OS is defined as the time from the first dose of study treatment to death from any cause. Subjects who are alive at the time of analysis will be censored at the date of last follow-up. |
| Objective Response Rate (ORR) | From enrollment to the end of monitoring at 2 years. | ORR is defined as the proportion of subjects who achieve a complete response (CR) or partial response (PR) as per RECIST v1.1. |
| Duration of Response (DoR) | From enrollment to the end of monitoring at 2 years. | DoR is defined as the time from the first documentation of CR or PR to the first documentation of disease progression or death. |
| Disease Control Rate (DCR) | From enrollment to the end of monitoring at 2 years. | DCR is defined as the proportion of subjects who achieve CR, PR, or stable disease (SD) as their best overall response. |
| The incidence of adverse events | From enrollment to the end of monitoring at 2 years | Incidence, nature, and severity of adverse events (AEs), graded according to NCI-CTCAE v5.0, including immune-related AEs and serious AEs. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Immune-Related Adverse Events (irAEs) | From enrollment to the end of monitoring at 2 years | Occurrence and grade of immune-related adverse events as defined by pre-specified criteria, including rash, colitis, hepatitis, endocrinopathies, and pneumonitis. |
| Biomarker Analysis | From enrollment to the end of monitoring at 2 years | Tumor tissues were detected for PD-L1 using IHC. Potential biomarkers such as CD3+ and CD8+ were detected in peripheral blood. |
Countries
China
Contacts
Primary ContactZhijie Wang, MD
Outcome results
None listed