This is a prospective, open-label, exploratory clinical study to evaluate the safety and preliminary efficacy of allogeneic natural killer (NK) cell injection combined with standard maintenance therapy in patients with locally advanced or metastatic solid tumors. The study consists of 5 cohorts: Cohort 1 (advanced non-squamous NSCLC with NK cells + PD-(L)1 inhibitor + pemetrexed), Cohort 2 (advanced colorectal adenocarcinoma with NK cells + cetuximab/bevacizumab + capecitabine), Cohort 3 (lymphodepletion exploration cohort with fludarabine + cyclophosph preconditioning followed by NK cells + PD-(L)1 inhibitor + pemetrexed), Cohort 4 (advanced HCC with NK cells + VEGF + PD-(L)1), and Cohort 5 (advanced GC with NK cells + PD-(L)1 + S-1).
This study is designed as a prospective cohort study to evaluate the safety and efficacy of allogeneic NK cell injection combined with standard maintenance therapy in advanced solid tumor patients. Study Design: Cohort 1: Advanced non-squamous non-small cell lung cancer (NSCLC) without driver gene mutations, receiving NK cells + PD-(L)1 inhibitor + pemetrexed as first-line maintenance therapy (3-week cycles) Cohort 2: Advanced colorectal adenocarcinoma, receiving NK cells + cetuximab/bevacizumab + capecitabine as first-line maintenance therapy (2-week cycles) Cohort 3: Lymphodepletion exploration cohort for advanced non-squamous NSCLC, receiving fludarabine + cyclophosphamide preconditioning followed by NK cells + PD-(L)1 inhibitor + pemetrexed (3-week cycles) Each cohort includes a safety lead-in phase (3 patients) followed by an expansion phase (3-6 patients). Dose-limiting toxicity (DLT) will be assessed during the first cycle. Cohort 4 :advanced HCC with NK cells + VEGF + PD-(L)1 (3-week cycles). Cohort 5 :advanced GC with NK cells + PD-(L)1 + S-1 (2-week cycles).
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
42
Administered according to standard clinical practice and product labeling
3-week cycles
2-week cycles
3-week cycles
2-week cycles
Dose-Limiting Toxicity (DLT)
Incidence of DLT defined as: Grade 4-5 CRS or ICANS related to NK cells; Grade 3 CRS/ICANS not resolving to ≤Grade 2 within 7 days; Grade ≥3 non-hematologic toxicity not resolving to Grade 2 or baseline; Grade 4 hematologic toxicity not resolving to Grade 2 or baseline within DLT observation period
Time frame: During the first treatment cycle (21 days for Cohorts 1&3, 14 days for Cohort 2)
Adverse Events (AE)
Incidence and severity of treatment-emergent adverse events assessed by NCI-CTCAE v5.0
Time frame: From first dose through 30 days after last dose
Progression-Free Survival (PFS)
Progression-Free Survival (PFS)
Time frame: From enrollment until disease progression or death, up to 2 years
Objective Response Rate (ORR)
Proportion of patients achieving complete response (CR) or partial response (PR) per RECIST 1.1
Time frame: From enrollment until disease progression or death, up to 2 years
Duration of Response (DOR)
From date of first documented response (CR or PR) until date of first documented progression or date of death from any cause, whichever came first, assessed up to 24 months
Time frame: up to 24 months
Disease Control Rate (DCR)
Proportion of patients with CR, PR, or stable disease (SD)
Time frame: Up to 2 years
Circulating Tumor DNA (ctDNA) Changes
Changes in peripheral blood ctDNA levels
Time frame: Baseline, every 6 weeks during treatment (up to approximately 12 months), and at end of treatment, up to 12 months
Quality of Life EORTC QLQ-C30
Changes in EORTC QLQ-C30 scores
Time frame: Baseline, every 6 weeks during treatment, and at end of treatment, up to 24 months
Quality of Life EORTC EQ-5D-5L
Changes in EQ-5D-5L utility index score
Time frame: Baseline, every 6 weeks during treatment, and at end of treatment,up to 24 months
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