Combination of Anti-PD-1 and NK Immunotherapy for Recurrent Solid Tumors

Study Overview
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Brief Summary
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The aim of this study is the safety and efficacy of anti-PD-1 plus NK immunotherapy to multiple solid tumors.

Detailed Description
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By enrolling patients with solid tumors adapted to enrolled criteria, this study will document for the first time the safety and the short and long term efficacy of the combined therapy using anti-PD-1 and natural killer (NK) cells. The safety will be evaluated by statistics of adverse reactions. The efficacy will be evaluated according to local relief degree, progress free survival (PFS) and overall survival (OS).

Official Title
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Combination of Anti-PD-1 and NK Immunotherapy for Recurrent Solid Tumors

Conditions
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Malignant Solid Tumour

Intervention / Treatment
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* Drug: Pembrolizumab
* Biological: NK immunotherapy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: All standard therapies have failed according to NCCN guidelines or the patient refuses standard therapies after cancer recurrence Progression after chemotherapy or appropriate TKI treatment for those patients with an EGFR-sensitizing mutation or ALK rearrangement KPS ≥ 70, lifespan > 3 months, PD-L1 TPS of 1% or greater Platelet count ≥ 80×10^9/L，white blood cell count ≥ 3×10^9/L, neutrophil count ≥ 2×10^9/L, hemoglobin ≥ 80 g/L Exclusion Criteria: Patients with cardiac pacemaker Patients with brain metastasis Patients with grade 3 hypertension or diabetic complication, severe cardiac and pulmonary dysfunction, myelosuppression, autoimmune disease, pneumonitis Previous treatment with a therapeutic antibody against CTLA4, PD-L1, or PD-1, or PD-L1/PD-1 pathway-targeting agents.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Pembrolizumab and NK immunotherapy<br>In this group, the patients will receive regular Pembrolizumab first to control tumor burden; then NK immunotherapy will be given. The check indexes are CT scan and blood tests (including tumor markers, lymphocyte subsets and circulating tumor cell). | Drug: Pembrolizumab<br>* Patients received i.v. pembrolizumab (10 mg/kg) on day 1 of a 21-day cycle, until disease progression, discontinuation due to unacceptable toxicity, withdrawal of consent or study closure<br>* Other names: Keytruda;Biological: NK immunotherapy<br>* Each treatment: about 10 billion cells in all, infusion in 3 times, i.v.<br>|
| Active Comparator: Pembrolizumab<br>In this group, the patients will receive regular Pembrolizumab to control tumor burden. The check indexes are CT scan and blood tests (including tumor markers, lymphocyte subsets and circulating tumor cell). | Drug: Pembrolizumab<br>* Patients received i.v. pembrolizumab (10 mg/kg) on day 1 of a 21-day cycle, until disease progression, discontinuation due to unacceptable toxicity, withdrawal of consent or study closure<br>* Other names: Keytruda;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| PFS | PFS was defined as the interval between treatment initiation and local relapse, | 2 year | 
| OS | OS was calculated as the interval from treatment initiation to death. | 3 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| PD-1 | Peripheral blood (6 mL) was obtained from healthy donors and patients before treatment and 90 days after treatment for the detection of PD-1 | 3 months | 
| Tumor size | The tumor responses of the enrolled patients were assessed by CT in accordance with RECIST v1.1.Institute Common Terminology Criteria for Adverse Events (v4.0). | 3 months | 
| CEA | CEA was evaluated by a chemiluminescent immunoassay before treatment and 90 days after treatment. | 3 months | 
| CTC | The absolute number of CD45-CK+ CD326+ cells was used to quantitate the CTC levels. | 3 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Solid tumor, Anti-PD-1, NK immunotherapy