A Randomized, Multicenter, Open-label, Phase II Study of Platinum-Containing Chemotherapy and Sintilimab With or Without Autologous Cytokine-induced Killer Cell Immunotherapy in Stage IV Non-Small Cell Lung Cancer Subjects
试验速览
- 阶段
- 2 期
- 状态
- 进行中（未招募）
- 入组人数
- 156
- 试验地点
- 1
- 主要终点
- Objective Response Rate (ORR)
研究概览
简要总结
This prospective, multi-center, open-label, phase II, randomized controlled trial (CCICC-002b) is to evaluate the efficacy and safety of autologous cytokine-induced killer cell immunotherapy in combination with PD-1 inhibitor and platinum-containing chemotherapy in the first-line treatment of stage IV non-small cell lung cancer (NSCLC).
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Signed written informed consent prior to any trial-related procedures.
- •Age ≥18 and ≤75 years.
- •Histologically or cytologically confirmed stage IV NSCLC (IASLC/UICC 8th edition TNM staging) with no prior systemic therapy for advanced disease.
- •For enrolled adenocarcinoma patients: Absence of EGFR-sensitive mutations and ALK gene fusion alterations confirmed by histological specimens.
- •At least one radiologically measurable lesion per RECIST v1.
- •Lesions within prior radiotherapy fields may be considered measurable if progression is confirmed.
- •No prior systemic antitumor therapy for advanced/metastatic disease. Subjects who received:
- •Platinum-based adjuvant/neoadjuvant chemotherapy, or
- •Definitive chemoradiotherapy for limited-stage disease are eligible if disease progression/recurrence occurred ≥6 months after last chemotherapy.
- •Asymptomatic or stable brain metastases after local treatment are permitted if all criteria are met:
- •Measurable extracranial lesions
- •No CNS symptoms or symptom stability for ≥2 weeks
- •No corticosteroids required, OR discontinued corticosteroids ≥7 days before first dose, OR stable corticosteroid dose ≤10 mg/day prednisone equivalent for ≥7 days.
- •Palliative radiotherapy (including brain RT for symptomatic metastases) is allowed if completed ≥1 week before first dose and radiation-related toxicities have recovered to ≤Grade 1 (CTCAE v5.0, excluding alopecia).
- •ECOG performance status 0-
- •Life expectancy >3 months.
- •Adequate organ function meeting all laboratory criteria:
- •Absolute neutrophil count (ANC) ≥1.5×10⁹/L without granulocyte colony-stimulating factor support within 14 days.
- •Platelets ≥100×10⁹/L without transfusion within 14 days.
- •Hemoglobin >9 g/dL without transfusion or erythropoietin within 14 days.
- •Total bilirubin ≤1.5×ULN.
- •AST/ALT ≤2.5×ULN (≤5×ULN if liver metastases present).
- •Serum creatinine ≤1.5×ULN AND creatinine clearance (Cockcroft-Gault formula) ≥60 mL/min.
- •INR/PT ≤1.5×ULN.
- •Normal thyroid function (TSH within normal range). Subjects with baseline TSH outside normal range may enroll if FT3/FT4 are normal.
- •Normal myocardial enzyme profile.
- •For women of childbearing potential: Negative urine/serum pregnancy test within 3 days prior to first dose (Cycle 1 Day 1). Non-childbearing potential is defined as ≥1 year post-menopause, surgically sterilized, or hysterectomy.
- •All subjects (regardless of gender) at risk of conception must use highly effective contraception (failure rate <1% annually) during treatment and for 120 days (or 180 days per protocol) after last dose.
排除标准
- •Pathologically confirmed small cell lung cancer (SCLC), including mixed SCLC-NSCLC histology.
- •Prior radiotherapy meeting any of the following:
- •Radiation to ≥30% of bone marrow within 14 days before first dose
- •Lung radiation >30 Gy within 6 weeks before treatment (subjects must have recovered to ≤Grade 1 toxicity, no corticosteroid requirement, and no history of radiation pneumonitis)
- •Palliative radiotherapy completed ≤7 days before first dose
- •Diagnosis of malignancies other than NSCLC within 5 years before first dose (except cured basal cell carcinoma, squamous cell carcinoma, or resected carcinoma in situ).
- •Current participation in interventional clinical trials or receipt of investigational drugs/devices within 4 weeks before first dose.
- •Prior therapy with anti-PD-1/PD-L1/PD-L2 agents or drugs targeting other T-cell co-stimulatory/checkpoint pathways (e.g., CTLA-4, OX-40, CD137).
- •Systemic treatment with Chinese herbal medicines (for lung cancer indications) or immunomodulatory agents (e.g., thymosin, interferon, interleukin) within 14 days before first dose (except local pleural control).
- •Active autoimmune disease requiring systemic treatment (e.g., disease-modifying agents, corticosteroids, immunosuppressants) within 2 years before first dose. Replacement therapies (e.g., thyroid hormone, insulin, physiologic corticosteroids) are permitted.
- •Systemic corticosteroids (>10 mg/day prednisone equivalent) or immunosuppressive therapy within 7 days before first dose (excluding topical/nasal/inhaled corticosteroids).
- •*Note: Physiologic corticosteroid doses (≤10 mg/day prednisone equivalent) are allowed.*
- •Clinically uncontrolled pleural/peritoneal effusion (subjects with stable effusion not requiring drainage or ≥3 days post-drainage may enroll).
- •History of allogeneic organ transplantation (except corneal transplants) or hematopoietic stem cell transplantation.
- •Known hypersensitivity to sintilimab, pemetrexed, nab-paclitaxel, carboplatin, or their excipients.
- •Failure to recover from prior intervention-related toxicities (≤Grade 1 or baseline, excluding alopecia/fatigue) before treatment initiation.
- •Known HIV infection (HIV 1/2 antibody positive).
- •Untreated active hepatitis B (HBsAg-positive with HBV-DNA > upper limit of normal [ULN] at local laboratory).
- •*Exceptions:*
- •HBV-DNA <1000 copies/ml (200 IU/ml) before first dose with ongoing antiviral prophylaxis during chemotherapy
- •Anti-HBc(+) subjects with HBsAg(-), anti-HBs(-), and undetectable HBV-DNA may enroll without prophylaxis but require close monitoring
- •Active HCV infection (HCV antibody-positive with detectable HCV-RNA).
- •Live vaccination within 30 days before Cycle 1 Day
- •*Note: Inactivated vaccines (e.g., seasonal influenza) are permitted; live attenuated vaccines (e.g., nasal flu vaccine) are prohibited.*
- •Pregnancy or lactation.
- •Severe uncontrolled systemic diseases including:
- •Symptomatic ECG abnormalities (e.g., complete left bundle branch block, ≥Grade 2 AV block, ventricular arrhythmias, atrial fibrillation)
- •Unstable angina, congestive heart failure (NYHA class ≥2)
- •Myocardial infarction within 6 months
- •Poorly controlled hypertension (SBP >140 mmHg/DBP >90 mmHg)
- •Non-infectious pneumonitis requiring steroids within 1 year or active interstitial lung disease
- •Active tuberculosis
- •Uncontrolled active infection requiring systemic therapy
- •Clinically active diverticulitis, abdominal abscess, gastrointestinal obstruction
- •Decompensated liver disease (e.g., cirrhosis, active hepatitis)
- •Poorly controlled diabetes (fasting glucose >10 mmol/L)
- •Urine protein ≥++ with 24-hour protein >1.0 g
- •Uncontrolled hypercalcemia (>1.5 mmol/L ionized calcium or corrected serum calcium >ULN)
- •Non-healing wounds/fractures
- •Psychiatric disorders impairing protocol compliance
- •Any condition that may interfere with study results, compromise subject safety, or preclude full participation as judged by the investigator.
研究组 & 干预措施
CIK cells + Sintilimab + Platinum-based doublet chemotherapy
Participants receive CIK cells for up to 8 cycles, in combination with sintilimab plus platinum-based chemotherapy (carboplatin and albumin paclitaxel for squamous NSCLC, or carboplatin and pemetrexed for non-squamous NSCLC), intravenously, every 3 weeks, for up to four cycles, followed by maintenance therapy with sintilimab for squamous NSCLC, and sintilimab plus pemetrexed for non-squamous NSCLC until disease progression or unacceptable toxicity or 2 years.
干预措施: CIK cells injection (Biological)
CIK cells + Sintilimab + Platinum-based doublet chemotherapy
Participants receive CIK cells for up to 8 cycles, in combination with sintilimab plus platinum-based chemotherapy (carboplatin and albumin paclitaxel for squamous NSCLC, or carboplatin and pemetrexed for non-squamous NSCLC), intravenously, every 3 weeks, for up to four cycles, followed by maintenance therapy with sintilimab for squamous NSCLC, and sintilimab plus pemetrexed for non-squamous NSCLC until disease progression or unacceptable toxicity or 2 years.
干预措施: Sintilimab Injection (Drug)
CIK cells + Sintilimab + Platinum-based doublet chemotherapy
Participants receive CIK cells for up to 8 cycles, in combination with sintilimab plus platinum-based chemotherapy (carboplatin and albumin paclitaxel for squamous NSCLC, or carboplatin and pemetrexed for non-squamous NSCLC), intravenously, every 3 weeks, for up to four cycles, followed by maintenance therapy with sintilimab for squamous NSCLC, and sintilimab plus pemetrexed for non-squamous NSCLC until disease progression or unacceptable toxicity or 2 years.
干预措施: Pemetrexed (Drug)
CIK cells + Sintilimab + Platinum-based doublet chemotherapy
Participants receive CIK cells for up to 8 cycles, in combination with sintilimab plus platinum-based chemotherapy (carboplatin and albumin paclitaxel for squamous NSCLC, or carboplatin and pemetrexed for non-squamous NSCLC), intravenously, every 3 weeks, for up to four cycles, followed by maintenance therapy with sintilimab for squamous NSCLC, and sintilimab plus pemetrexed for non-squamous NSCLC until disease progression or unacceptable toxicity or 2 years.
干预措施: Albumin paclitaxel (Drug)
CIK cells + Sintilimab + Platinum-based doublet chemotherapy
Participants receive CIK cells for up to 8 cycles, in combination with sintilimab plus platinum-based chemotherapy (carboplatin and albumin paclitaxel for squamous NSCLC, or carboplatin and pemetrexed for non-squamous NSCLC), intravenously, every 3 weeks, for up to four cycles, followed by maintenance therapy with sintilimab for squamous NSCLC, and sintilimab plus pemetrexed for non-squamous NSCLC until disease progression or unacceptable toxicity or 2 years.
干预措施: Carboplatin (Drug)
Sintilimab + Platinum-based doublet chemotherapy
Participants receive sintilimab plus platinum-based chemotherapy (carboplatin and albumin paclitaxel for squamous NSCLC, or carboplatin and pemetrexed for non-squamous NSCLC), intravenously, every 3 weeks, for up to four cycles, followed by maintenance therapy with sintilimab for squamous NSCLC, and sintilimab plus pemetrexed for non-squamous NSCLC until disease progression or unacceptable toxicity or 2 years.
干预措施: Sintilimab Injection (Drug)
Sintilimab + Platinum-based doublet chemotherapy
Participants receive sintilimab plus platinum-based chemotherapy (carboplatin and albumin paclitaxel for squamous NSCLC, or carboplatin and pemetrexed for non-squamous NSCLC), intravenously, every 3 weeks, for up to four cycles, followed by maintenance therapy with sintilimab for squamous NSCLC, and sintilimab plus pemetrexed for non-squamous NSCLC until disease progression or unacceptable toxicity or 2 years.
干预措施: Pemetrexed (Drug)
Sintilimab + Platinum-based doublet chemotherapy
Participants receive sintilimab plus platinum-based chemotherapy (carboplatin and albumin paclitaxel for squamous NSCLC, or carboplatin and pemetrexed for non-squamous NSCLC), intravenously, every 3 weeks, for up to four cycles, followed by maintenance therapy with sintilimab for squamous NSCLC, and sintilimab plus pemetrexed for non-squamous NSCLC until disease progression or unacceptable toxicity or 2 years.
干预措施: Albumin paclitaxel (Drug)
Sintilimab + Platinum-based doublet chemotherapy
Participants receive sintilimab plus platinum-based chemotherapy (carboplatin and albumin paclitaxel for squamous NSCLC, or carboplatin and pemetrexed for non-squamous NSCLC), intravenously, every 3 weeks, for up to four cycles, followed by maintenance therapy with sintilimab for squamous NSCLC, and sintilimab plus pemetrexed for non-squamous NSCLC until disease progression or unacceptable toxicity or 2 years.
干预措施: Carboplatin (Drug)
结局指标
主要结局
Objective Response Rate (ORR)
时间窗: Time Frame: Up to 24 months
ORR was defined as the percentage of patients with a confirmed complete (CR) or partial response (PR) Per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 as assessed by the investigator.
次要结局
- Progression-free survival (PFS)(up to 24 months)
- Overall Survival (OS)(up to 3 years)
- Duration of response (DOR)(up to 24 months)
- Disease Control Rate (DCR)(up to 24 months)
- Number of Participants Who Experienced an Adverse Event (AE)(up to 24 months (Serious AEs: Up to 90 days after last dose of study treatment (Other AEs: Up to 30 days after last dose of study treatment))
- Number of Participants Who Discontinued Any Study Drug Due to an AE(up to 24 months)