Extensive-stage Small-cell Lung Cancer
Conditions
Brief summary
This is a Phase II, single arm, multicenter study designed to evaluate the safety and efficacy of low-dose radiotherapy (LDRT) concurrent cisplatin/carboplatin plus etoposide with serplulimab in participants who have extensive-stage small cell lung cancer (ES-SCLC) and are chemotherapy-navïe for their extensive-stage disease.
Detailed description
Enrolled patients will receive the following treatment regimen: LDRT-concurrent cisplatin/carboplatin plus etoposide in combination with serplulimab. The induction period consists of 4 cycles of 21 days each. Low-dose radiotherapy at 15Gy/5f will be performed concurrently from Day 1 to Day 5 (D1-D5) of Cycle 1. An efficacy assessment will be performed at the end of Cycle 2 and one week before the start of Cycle 3. For patients with primary lung lesions (intrathoracic lesions) evaluated as small PR (tumor shrinkage \< 80%)/SD/PD, low-dose radiotherapy at 15Gy/5f will be performed in addition to serplulimab with chemotherapy in Cycle 3. For subjects evaluated as PD/SD/PR with extrathoracic residual metastases, low-dose radiotherapy at 15Gy/5f will be performed in addition to serplulimab with chemotherapy in Cycle 4. Definition of extrathoracic lesions for radiotherapy: Metastases to liver, metastases to adrenals and metastases to lymph nodes (at the discretion of the investigator). After the induction period, the subjects will continue to receive maintenance treatment with serplulimab. Prophylactic cranial irradiation (PCI) is allowed for treatment according to local standard of care. Patients will be treated until loss of clinical benefit, unacceptable toxicity, withdrawal of informed consent, or death, whichever occurs first.
Interventions
DRUGserplulimab
Serplulimab will be administered by intravenous infusion at a dose of 4.5mg/kg on Day 1 of each 21-day cycle until unacceptable toxicity or loss of clinical benefit as determined by the investigator after an integrated assessment of radiographic and biochemical data, and clinical status.
DRUGCisplatin
Cisplatin will be administered as intravenous infusion at a dose of 75 mg per meter squared (75 mg/m\^2) after completion of serplulimab on Day 1 of each 21-day cycle during the induction phase (Cycles 1-4).
DRUGCarboplatin
Carboplatin will be administered as intravenous infusion at a dose of area under the concentration-time curve (AUC) of 5 mg/mL/min on Day 1 of each 21-day cycle during the induction phase (Cycles 1-4).
DRUGEtoposide
Etoposide will be administered intravenously at a dose of 100 mg/m\^2 on Days 1, 2 and 3 of each 21-day cycle during the induction phase (Cycles 1-4).
RADIATIONThoracic radiation therapy (TRT)
Participants will receive concurrent low-dose radiotherapy treatment, in once daily fractions, 3 Gy per fraction, to a target dose of 15 Gy in 5 fractions from Day 1-Day 5 in the first cycle, third cycle（ For patients with primary lung lesions (intrathoracic lesions) evaluated as small PR (tumor shrinkage \< 80%)/SD/PD），forth cycle（for subjects evaluated as PD/SD/PR with extrathoracic residual metastases).
Sponsors
Sichuan University
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
Main Inclusion Criteria: 1. Histologically or cytologically confirmed ES-SCLC 2. No prior treatment for ES-SCLC 3. Measurable disease, as defined by RECIST v1.1. Previously irradiated lesions can be considered as measurable disease only if progressive disease has been unequivocally documented at that site since radiation. 4. ECOG performance status of 0 or 1 5. Life expectancy \>= 3 months 6. Adequate hematologic and end-organ function 7. For participants receiving therapeutic anticoagulation: stable anticoagulant regimen 8. Negative human immunodeficiency virus (HIV) test at screening 9. Negative hepatitis B surface antigen (HBsAg) test at screening 10. Positive hepatitis B surface antibody (HBsAb) test at screening, or negative HBsAb at screening accompanied by either of the following: Negative total hepatitis B core antibody (HBcAb), or positive total HBcAb test followed by a negative hepatitis B virus (HBV) DNA test. The HBV DNA test will be performed only for participants who have a negative HBsAg test, a negative HBsAb test, and a positive total HBcAb test. 11. Negative hepatitis C virus (HCV) antibody test at screening, or positive HCV antibody test followed by a negative HCV RNA test at screening. The HCV RNA test will be performed only for participants who have a positive HCV antibody test. 12. For women of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraception 13. For men: agreement to remain abstinent (refrain from heterosexual intercourse) or use a condom, and agreement to refrain from donating sperm Main
Exclusion criteria
1. Symptomatic, untreated, or actively progressing central nervous system (CNS) metastases 2. Participants with pulmonary artery invasion 3. History of leptomeningeal disease 4. Uncontrolled tumor-related pain 5. Uncontrolled pleural effusion, pericardial effusion, or ascites requiring recurrent drainage procedures 6. Uncontrolled or symptomatic hypercalcemia 7. Active or history of autoimmune disease or immune deficiency 8. History of idiopathic pulmonary fibrosis, organizing pneumonia, drug-induced pneumonitis, or idiopathic pneumonitis, or evidence of active pneumonitis on screening chest computed tomography (CT) scan 9. Active tuberculosis 10. Significant cardiovascular disease within 3 months prior to initiation of study treatment, unstable arrhythmia, or unstable angina 11. History of malignancy other than small cell lung cancer (SCLC) within 5 years prior to screening, with the exception of malignancies with a negligible risk of metastasis or death
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Progression-free survival (PFS) | Baseline up to approximately 24 months | The time from the date of first dosing of serplulimab to the first appearance of objective disease progression (according to RECIST1.1) or death from any cause (if it occurs before disease progression). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Overall Survival (OS) | Baseline up to approximately 24 months | The time from the date of first dosing of serplulimab to death from any cause. |
| OS Rate at 1 Year and 2 Years | Baseline to 2 years or death, whichever occurs first. | OS rate at 1 year and 2 years, defined as the proportion of patients who have not experienced death from any cause at 1 year and 2 years. |
| PFS Rate at 6 Months and 1 Year | Baseline up to 1 year | PFS rate at 6 months and 1 year, defined as the proportion of patients who have not experienced disease progression or death from any cause at 6 months and 1 year separately, as determined by the investigator according to RECIST v1.1. |
| Disease control rate (DCR) | Baseline up to approximately 24 months | defined as the proportion of participants who have a best overall response of CR or PR or stable disease (SD), as determined by the investigator according to RECIST v1.1. |
| Percentage of Participants With Adverse Event | Baseline up to approximately 36 months | • The incidence and severity of adverse events, with severity determined according to the U.S. National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events version 5.0 (CTCAEv5.0) |
| Duration of response (DOR) | Baseline to disease progression or death from any cause (whichever occurs first)(up to approximately 24 months) | defined as the time from the first occurrence of a documented objective response to disease progression or death from any cause (whichever occurs first), as determined by the investigator according to RECIST v1.1. |
Countries
China
Contacts
Primary ContactZhuoran Yao, MD
Backup ContactLi Li, BA
Outcome results
None listed