Allogeneic NK Cell Therapy Combined With Standard Maintenance Treatment in Advanced Solid Tumors

Official title

An Exploratory Clinical Study to Evaluate the Safety and Efficacy of Allogeneic NK Cell Injection Combined With Standard Maintenance Therapy in Subjects With Locally Advanced or Metastatic Solid Tumors

Overview

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 three 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), and Cohort 3 (lymphodepletion exploration cohort with fludarabine + cyclophosph preconditioning followed by NK cells + PD-(L)1 inhibitor + pemetrexed).

Detailed description

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.

Interventions

• Biological NK Cells
  Administered according to standard clinical practice and product labeling
• Biological NK cells + PD-(L)1 inhibitor + pemetrexed as first-line maintenance therapy
  3-week cycles
• Biological NK cells + cetuximab/bevacizumab + capecitabine as first-line maintenance therapy
  2-week cycles

Primary outcome measures

• Dose-Limiting Toxicity (DLT) [Time frame: During the first treatment cycle (21 days for Cohorts 1&3, 14 days for Cohort 2)]
• Adverse Events (AE) [Time frame: From first dose through 30 days after last dose]

Secondary outcome measures (7)

• Progression-Free Survival (PFS) [Time frame: From enrollment until disease progression or death, up to 2 years]
• Objective Response Rate (ORR) [Time frame: From enrollment until disease progression or death, up to 2 years]
• Duration of Response (DOR) [Time frame: up to 24 months]
• Disease Control Rate (DCR) [Time frame: Up to 2 years]
• Circulating Tumor DNA (ctDNA) Changes [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 [Time frame: Baseline, every 6 weeks during treatment, and at end of treatment, up to 24 months]
• Quality of Life EORTC EQ-5D-5L [Time frame: Baseline, every 6 weeks during treatment, and at end of treatment,up to 24 months]

Eligibility criteria

Inclusion criteria

• Age 18-75 years, either gender
• Cohort 1 \& 3: Histologically or cytologically confirmed locally advanced unresectable or metastatic non-squamous NSCLC (Stage IIIB-IV) without known actionable driver gene mutations (including but not limited to: EGFR sensitizing mutations, ALK rearrangement, ROS1 rearrangement, BRAF V600E mutation, KRAS mutation)
• Cohort 1 \& 3: Previously received 4-6 cycles of first-line induction therapy with PD-(L)1 inhibitor combined with pemetrexed plus platinum, with radiographic assessment of non-progressive disease (CR, PR, or SD per RECIST 1.1)
• Cohort 2: Histologically or cytologically confirmed locally advanced unresectable or metastatic colorectal adenocarcinoma (unresectable Stage III or Stage IV per AJCC 8th edition)
• Cohort 2: Previously received 6-9 cycles of first-line induction therapy with cetuximab or bevacizumab combined with FOLFOX or FOLFIRI, with radiographic assessment of non-progressive disease (CR, PR, or SD per RECIST 1.1)
• Prior neoadjuvant/adjuvant chemotherapy allowed if disease recurrence or metastasis occurred >6 months after last chemotherapy dose
• At least one measurable lesion per RECIST 1.1 (except patients who achieved CR during induction therapy): non-lymph node lesion ≥1.0 cm in longest diameter, or lymph node lesion ≥1.5 cm in short diameter; lesions treated with local therapy (radiation or interventional) cannot be target lesions unless progression is documented
• Adequate bone marrow and organ function:

• ANC ≥1.5×10⁹/L; Platelet >90×10⁹/L; Hemoglobin >9 g/dL
• Liver function: Total bilirubin <1.5×ULN; ALT and AST <3×ULN (<5×ULN if liver metastases present)
• Renal function: Serum creatinine ≤1.5×ULN
• Coagulation: PT, APTT, INR <1.5×ULN
• ECOG performance status 0-1
• Life expectancy ≥3 months
• Non-pregnant, non-lactating; women of childbearing potential must have negative serum pregnancy test within 7 days before cell infusion and agree to use reliable contraception during study and for 6 months after last infusion; men with partners of childbearing potential must agree to use reliable contraception
• Voluntary informed consent and able to comply with follow-up

Exclusion criteria

• Prior treatment with other cellular therapy products (DC, CIK, T cells, NK cells, CAR-T, etc.) except this product
• Other malignancies within 5 years before screening (completely resolved carcinoma in situ and slowly progressing malignancies as determined by investigator excluded)
• Symptomatic moderate to severe third-space effusion requiring therapeutic drainage
• Gastrointestinal perforation, fistula, or intra-abdominal abscess within 6 months
• Significant cardiovascular disease history including
• Arterial or venous thrombotic events within 6 months before enrollment (CVA, DVT, PE, etc.)
• Active infection (viral, bacterial, fungal) currently being treated, or any infection requiring IV antibiotics for ≥7 days within past 6 weeks, or oral antibiotics within past 1 week
• Active autoimmune disease or history of severe autoimmune disease requiring long-term immunosuppression
• Participation in other interventional clinical trials within 3 months
• Toxicities from prior interventions not resolved to Grade ≤2 (alopecia excluded)
• Untreated chronic active hepatitis B, chronic HBV carriers with HBV DNA ≥1000 copies/mL; HCV antibody positive with HCV-RNA positive; HIV antibody positive; syphilis antibody positive
• Any other condition deemed by investigator to make subject unsuitable for study participation

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Non-randomized

Model

Single group

Masking

Open label

Primary purpose

Treatment

Study locations

Center list to be confirmed — check the primary protocol.

Identifiers

NCT: NCT07551778 · BOETech

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗