Non-small Cell Lung Cancer MetastaticPhase 2CCICC-002bNCT04836728
Phase II Study of Chemotherapy and PD-1 Inhibitor Combination With Autologous CIK Cell Immunotherapy to Treat Lung Cancer
A Phase 2 study testing CIK cells injection, Sintilimab Injection and Pemetrexed in people with Non-small Cell Lung Cancer Metastatic and First-line Treatment, run by Tianjin Medical University Cancer Institute and Hospital at 1 site in China.
Trial summary
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… Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Non-small Cell Lung Cancer Metastatic, First-line Treatment
- What is being tested?
- CIK cells injection, Sintilimab Injection and Pemetrexed
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 156 participants
- Where
- 1 siteChina
- Study dates
- 31 Mar 2021to 31 Dec 2026
- Phase
- Phase 2
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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:
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- 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.
Who cannot join
- 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).
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- 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 1. *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.
Trial locations and contacts
1 site in 1 country.
China1 site
Tianjin Medical University Cancer Institute and Hospital
Tianjin, Tianjin Municipality, 300060
About this study
Official title: 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
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).
- Being tested
- CIK cells injection, Sintilimab Injection, Pemetrexed, Albumin paclitaxel, Carboplatin
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CIK cells injectionBiological
Also called Autologous cytokine-induced killer cells
CIK cells, more than 1x10^10 (10 billion ), intravenous infusion, d14, Q3W.
Sintilimab InjectionDrug
Also called PD-1 inhibitor
200 mg, intravenous infusion, d1, every 3 weeks
PemetrexedDrug
Also called Pemetrexed injection
500 mg/m^2, intravenous infusion, d1, every 3 weeks
Albumin paclitaxelDrug
Also called Albumin paclitaxel Injection
260 mg/m^2, intravenous infusion, d1, every 3 weeks
CarboplatinDrug
Also called Carboplatin injection
AUC 5, intravenous infusion, d1, every 3 weeks
| Study group | Role | What they receive |
|---|---|---|
| CIK cells + Sintilimab + Platinum-based doublet chemotherapy | Experimental | 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. Receives: Biological: CIK cells injection; Drug: Sintilimab Injection; Drug: Pemetrexed; Drug: Albumin paclitaxel; Drug: Carboplatin |
| Sintilimab + Platinum-based doublet chemotherapy | Active comparator | 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. Receives: Drug: Sintilimab Injection; Drug: Pemetrexed; Drug: Albumin paclitaxel; Drug: Carboplatin |
What is being measured
The primary outcome is the main question the study is designed to answer.
Objective Response Rate (ORR)
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.
Measured: Time Frame: Up to 24 months
Secondary outcomes (6)
Progression-free survival (PFS)
PFS was defined as the time from the initial treatment to the first occurrence of disease progression or all-cause death (whichever occurs first) assessed by the investigator according to RECIST v1.1.
Measured: up to 24 months
Overall Survival (OS)
OS was defined as the time from the initial treatment until the date of death due to any cause.
Measured: up to 3 years
Duration of response (DOR)
DOR was defined as first documented evidence of a CR or PR until PD or death as determined by the investigator according to RECIST v1.1.
Measured: up to 24 months
Disease Control Rate (DCR)
DCR was defined as the proportion of patients with the best overall response of CR, PR, and stable disease (SD) as determined by the investigator according to RECIST 1.1.
Measured: up to 24 months
Number of Participants Who Experienced an Adverse Event (AE)
An AE was defined as any untoward medical occurrence in a study participant administered with study drug and which does not necessarily have to have a causal relationship with this study drug. The number of participants who experienced an AE is presented.
Measured: 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
An AE was defined as any untoward medical occurrence in a study participant administered with study drug and which does not necessarily have to have a causal relationship with this study drug. The number of participants who discontinued any randomized study drug due to an AE is presented.
Measured: up to 24 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Apr 2021
- Study start31 Mar 2021
- Primary completion30 Apr 2024
- Study completion31 Dec 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Non-small Cell Lung Cancer MetastaticStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 156 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Tianjin Medical University Cancer Institute and Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Liang Liu, MD. Ph.D, Study director, Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04836728
- Sponsor's protocol ID
- E20210014
- Acronym
- CCICC-002b
- Status last verified
- Feb 2025
- First submitted
- 6 Apr 2021
- Last updated
- 13 Mar 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: This is a multicenter, prospective clinical trial. Eight centers provide data to each other.
Publications
Zhou J, Bie H, You Y, Li J, Liu J, Li S, Huang H, Zhou L, Hui Z, Zhang W, Meng Y, Lin H, Zheng L, Qi Y, Ji Z, Yu W, Wang M, Ren X, Yan C. Circulating CD28-KLRG1+CD8+ T cells involve in systemic and local immunity that predicts chemoimmunotherapy outcomes in advanced NSCLC. J Transl Med. 2026 Jun 22. doi: 10.1186/s12967-026-08484-5. Online ahead of print.
PubMed 42332718