Phase II Study of Chemotherapy and PD-1 Inhibitor Combination With Autologous CIK Cell Immunotherapy to Treat Lung Cancer

Prior treatment

• 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
• 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).
• 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.\*
• Failure to recover from prior intervention-related toxicities (≤Grade 1 or baseline, excluding alopecia/fatigue) before treatment initiation.
• Live vaccination within 30 days before Cycle 1 Day 1. \*Note: Inactivated vaccines (e.g., seasonal influenza) are permitted; live attenuated vaccines (e.g., nasal flu vaccine) are prohibited.\*

Other illness

• Pathologically confirmed small cell lung cancer (SCLC), including mixed SCLC-NSCLC histology.
• 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).
• 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.
• History of allogeneic organ transplantation (except corneal transplants) or hematopoietic stem cell transplantation.
• Known hypersensitivity to sintilimab, pemetrexed, nab-paclitaxel, carboplatin, or their excipients.
• Known HIV infection (HIV 1/2 antibody positive).
• Active HCV infection (HCV antibody-positive with detectable HCV-RNA).
• Any condition that may interfere with study results, compromise subject safety, or preclude full participation as judged by the investigator.

Lab values

• 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
• 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

Other

• Clinically uncontrolled pleural/peritoneal effusion (subjects with stable effusion not requiring drainage or ≥3 days post-drainage may enroll).
• Pregnancy or lactation.

• 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 v1.1. 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 0-1.
• 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.