Small Cell Lung Cancer
Conditions
Keywords
Extensive-Stage Small Cell Lung Cancer, Immunotherapy, Allogeneic NK Cells, Natural Killer Cells, Maintenance Therapy, Randomized Controlled Trial
Brief summary
This research study is designed for patients with extensive-stage small cell lung cancer (ES-SCLC) who have already received four cycles of standard chemotherapy, with at least two cycles combined with immunotherapy, and have achieved disease control (stable disease, partial response, or complete response) at their last efficacy evaluation. In this study, participants will be randomly assigned to one of two groups: Group A will receive standard immunotherapy plus 1 to 3 courses of allogeneic natural killer (NK) cell therapy. Each course consists of six NK cell infusions given over 28 days. Group B will receive standard immunotherapy alone. All participants will continue treatment until their disease progresses or they experience unacceptable side effects. The immunotherapy agents used in this study are those recommended by major international and national clinical guidelines for extensive-stage SCLC, including but not limited to durvalumab, atezolizumab, serplulimab, and adebrelimab. The purpose of this study is to evaluate whether adding NK cell therapy to standard immunotherapy can provide additional benefits for patients with extensive-stage SCLC who have responded well to initial treatment.
Detailed description
This is a prospective study enrolling 42 patients with extensive-stage small cell lung cancer (ES-SCLC) who have completed four cycles of platinum-based doublet chemotherapy, with at least two cycles of immunotherapy combined with platinum-based doublet chemotherapy, and whose final efficacy assessment after the last cycle shows disease control (SD, PR, or CR). Patients will be adaptively randomized into two groups based on the results of prior efficacy analysis. Subjects will be randomly assigned to Group A or Group B. Patients in Group A will receive an immune checkpoint inhibitor (ICI) plus 1-3 courses of allogeneic natural killer (NK) cell therapy. One course of NK cell therapy is designed to consist of two cycles, with a total of six NK cell infusions within 28 days, specifically on Days 12, 13, and 14 of the first cycle and Days 26, 27, and 28 of the second cycle. In addition, on Day 1 of each 21-day cycle, patients will receive standard-of-care treatment with intravenous infusion of an immune checkpoint inhibitor. Patients in Group B will receive standard-of-care treatment with intravenous infusion of an immune checkpoint inhibitor on Day 1 of each 21-day cycle, and treatment will continue until disease progression or unacceptable toxicity occurs. After signing the written informed consent form, patients will receive study treatment per protocol until disease progression or intolerable adverse events develop. The immune checkpoint inhibitors used in this study are those recommended for extensive-stage SCLC in the NCCN, ESMO, and CSCO guidelines, including but not limited to durvalumab, atezolizumab, serplulimab, and adebrelimab.
Interventions
BIOLOGICALAllogeneic Natural Killer Cells
Allogeneic NK cells derived from healthy donors, expanded and activated ex vivo. One course consists of two cycles with 6 IV infusions over 28 days: Days 12, 13, 14 (Cycle 1) and Days 26, 27, 28 (Cycle 2). Patients receive 1-3 courses.
DRUGImmune Checkpoint Inhibitor
Immune checkpoint inhibitors recommended for extensive-stage SCLC by NCCN, ESMO, and CSCO guidelines, including but not limited to durvalumab, atezolizumab, serplulimab, adebrelimab, and toripalimab. Administered as IV infusion on Day 1 of each 21-day cycle.
Sponsors
Tianjin First Central Hospital
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Patients receive immune checkpoint inhibitor plus 1-3 courses of allogeneic natural killer (NK) cell therapy. Each course consists of 6 NK cell infusions over 28 days, combined with standard ICI on Day 1 of each 21-day cycle.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* 1: Male or female, aged 18 years or above 2: ECOG score 0-2 3: metastatic or extensive-stage small cell lung cancer (SCLC) confirmed by histology or cytology, followed by 4 cycles of platinum-based doublet-chemotherapy with at least 2 cycles of immune checkpoint inhibitor plus chemotherapy. And stable disease (SD), partial response (PR), or complete response (CR) as assessed by imaging (RECIST1.1 criteria) after the last treatment. (The checkpoint inhibitors used were those recommended by the NCCN, ESMO, and CSCO guidelines for extensivestage SCLC, including but not limited to: Duvalumab, atezolizumab, slulizumab, adbelimumab, toripalimab, etc.) 4: After standard concurrent chemoradiotherapy, LS-SCLC could be enrolled in this study if sensitive relapse (relapse more than 6 months after the end of first-line treatment) progressed to extensive-stage (Ed) and met the inclusion criteria No.3; 5: At least 4 weeks after major surgery or trauma, and the wound must be completely healed; At least 1 week after minor surgical procedures or trauma (e.g., tissue biopsy or fine-needle aspiration); 6: Objective measurable lesions according to RECIST 1.1 criteria; 7: predicted survival time ≥1 year; 8: bone marrow function: ANC≥1.5×109/L, HB≥70 g/L (blood transfusion allowed), PLT≥80×109/L; 9: Liver function: ALT≤3×ULN, AST≤3×ULN, TBIL≤2×ULN (patients with liver metastasis ALT≤5×ULN, AST≤5×ULN, TBIL≤2×ULN) Child-Pugh score ≤7; Renal function: uric acid \<500 μmol/L, serum creatinine \<1.7 mg/dL, proteinuria ≤2+ or ≤2g/24h, glomerular filtration rate (GFR) ≥60 ml/min/1.73m2; 10: no history of autoimmune diseases or current autoimmune diseases; 11: The subjects voluntarily participated in the study, signed the informed consent form, communicated well with the investigators, and completed the study in accordance with the protocol.
Exclusion criteria
* 1:Participate in other clinical trials or use other research drugs or equipment within 4 weeks of the first treatment. 2: During the screening period and previous imaging evaluation, active or untreated CNS metastasis was found by CT scanning or MRI. Patients with asymptomatic CNS metastasis who had been treated in the past can participate in this study as long as they meet all the following criteria: corticosteroids are not needed to treat CNS diseases, and imaging examination has not found any progress from the end of CNS directional treatment to the screening period。 If new asymptomatic CNS metastases are found in patients during the screening period, they must undergo radiotherapy and/or CNS metastasis surgery 3: The effusion in the third space with clinical symptoms needs repeated drainage (for example, less than once every four weeks), such as pericardial effusion, pleural effusion and peritoneal effusion that are still uncontrollable after pumping or other treatments 4: Live vaccine was inoculated within 30 days before the first administration of the study drug. Live vaccines include but are not limited to measles, mumps, minute needle, chickenpox/herpes zoster, rabies, BCG, typhoid vaccine, etc. Seasonal influenza vaccine for injection is generally inactivated virus vaccine, which is allowed to be used. 5: The patient is known to have other malignant tumors, which are progressing or need active treatment in the past 3 years (except for in situ cancer or localized prostate cancer supplemented by PSA test) 6: Received major surgery, open surgical biopsy or severe traumatic injury 28 days before joining the group. 7: Clinically related or preexisting interstitial lung disease 8: Severe unhealed wound, ulcer or fracture 9: Suffering from autoimmune diseases requiring systemic treatment in the past 2 years 10: Unstable systemic concomitant diseases (active infection, moderate and severe chronic obstructive pulmonary disease, poorly controlled hypertension, unstable angina pectoris, congestive heart failure, myocardial infarction, cerebrovascular accident, pulmonary embolism or untreated history of Grade 3 deep vein thrombosis (DVT) within 6 months, serious mental disorder requiring drug control, liver, kidney or other metabolic diseases, neuropsychiatric diseases such as Alzheimer's disease). 11: According to the judgment of the researcher, there are patients with accompanying diseases that seriously endanger the safety of patients or affect the completion of the study.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Progression free survival | Every 6 weeks from randomization until disease progression or death, up to approximately 24 months |
| Duration of Overall Response | From first documented response to disease progression, assessed every 6 weeks up to 24 months |
| Incidence and Severity of Treatment-Emergent Adverse Events (TEAEs) | From first dose through 30 days after last dose, up to approximately 24 months |
Secondary
| Measure | Time frame |
|---|---|
| overall survival | From randomization to death from any cause, assessed up to 24 months |
| Change from baseline in peripheral blood lymphocyte subsets (CD3+CD4+, CD3+CD8+, total CD3+, CD3-CD19+, and CD3-CD16+CD56+ cells) at Day 90 | Baseline and Day 90 |
| Change from baseline in serum cytokine levels (IL-2, IL-4, IL-6, IL-10, TNF-β, and IFN-γ) at Day 90 | Baseline and Day 90 |
| Change from baseline in serum tumor markers (SCC) at Day 90 | Baseline and Day 90 |
| Change from baseline in peripheral blood NK cell activity at Day 90 | Baseline and Day 90 |
Countries
China
Contacts
CONTACTGang Zhi Zhao
Outcome results
None listed