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

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

Study Overview

• Status: Completed
• Conditions: Malignant Solid Tumour
• Intervention / Treatment: Drug: Pembrolizumab; Biological: NK immunotherapy

Detailed Description

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).

• Study Type: Interventional
• Enrollment (Actual): 110
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• China
  • Guangdong
    • Guangzhou, Guangdong, China, 510665
      • Cancer Institute in Fuda cancer hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Pembrolizumab and NK immunotherapy; 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; 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; Other Names: Keytruda; Biological: NK immunotherapy; Each treatment: about 10 billion cells in all, infusion in 3 times, i.v.
Active Comparator: Pembrolizumab; 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; 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; Other Names: Keytruda

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Fuda Cancer Hospital, Guangzhou
• Collaborators: Shenzhen Hank Bioengineering Institute

Publications and helpful links

General Publications

• Lin M, Luo H, Liang S, Chen J, Liu A, Niu L, Jiang Y. Pembrolizumab plus allogeneic NK cells in advanced non-small cell lung cancer patients. J Clin Invest. 2020 May 1;130(5):2560-2569. doi: 10.1172/JCI132712.

Study record dates

Study Major Dates

• Study Start (Actual): July 1, 2016
• Primary Completion (Actual): July 1, 2017
• Study Completion (Actual): July 1, 2019

Study Registration Dates

• First Submitted: July 21, 2016
• First Submitted That Met QC Criteria: July 22, 2016
• First Posted (Estimate): July 25, 2016

Study Record Updates

• Last Update Posted (Actual): May 28, 2020
• Last Update Submitted That Met QC Criteria: May 26, 2020
• Last Verified: May 1, 2020

More Information

Terms related to this study

• Keywords: Anti-PD-1; Solid tumor; NK immunotherapy
• Additional Relevant MeSH Terms: Neoplasms; Antineoplastic Agents; Antineoplastic Agents, Immunological; Pembrolizumab
• Other Study ID Numbers: NK-PD-1