Anti-PD-1 Alone or Combined With Autologous Cell Therapy in Advanced NSCLC

Autologous Dendritic Cell-cytokine Induced Killer Cell Immunotherapy Combined Anti-PD1 in Advanced NSCLC: A Randomized Controlled Trial

A randomized controlled study to compared the clinical effects and safety of immunotherapy with dendritic cells and cytokine-induced killer cells administered with anti-PD-1 antibody in advanced NSCLC.

Study Overview

• Status: Completed
• Conditions: Neoplasms; Lung Cancer
• Intervention / Treatment: Biological: Anti-PD-1 plus DC-CIK; Biological: Anti-PD-1 alone

• Study Type: Interventional
• Enrollment (Actual): 60
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• China
  • Beijing, China, 100038
    • Capital Medical Unvierstiy Cancer Center/ Beijing Shijitan Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Histologically or cytologically confirmed advanced or metastatic NSCLC.
• Patients must have received previously standard therapy for that malignancy or declined to chemotherapy/radiotherapy.
• Estimated life expectancy > 3 months.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0,1 or 2.
• Age 18 to 80.
• Adequate hematologic function, with WBC ≥ 3000/microliter, hemoglobin ≥ 9 g/dL (it is acceptable to have had prior transfusion), platelets ≥ 75,000/microliter; PT-INR <1.5 (unless patient is receiving warfarin in which case PT-INR must be <3), PTT <1.5X ULN
• Adequate renal and hepatic function, with serum creatinine < 1.5 mg/ dL, bilirubin < 1.5 mg/dL (except for Gilbert's syndrome which will allow bilirubin ≤ 2.0 mg/dL), ALT and AST ≤ 2.5 x upper limit of normal.

Exclusion Criteria:

• Patients with a history of autoimmune disease, such as but not restricted to, inflammatory bowel disease, systemic lupus erythematosus, ankylosing spondylitis, scleroderma, or multiple sclerosis. Autoimmune related thyroid disease and vitiligo are permitted.
• Patients with serious intercurrent chronic or acute illness, such as cardiac disease (NYHA class III or IV), hepatic disease, or other illness considered by the Principal Investigator as unwarranted high risk for investigational drug treatment.
• Patients with a medical or psychological impediment to probable compliance with the protocol should be excluded.
• Concurrent (or within the last 5 years) second malignancy other than non melanoma skin cancer, cervical carcinoma in situ, controlled superficial bladder cancer, or other carcinoma in situ that has been treated.
• Presence of an active acute or chronic infection including: a urinary tract infection, HIV (as determined by ELISA and confirmed by Western Blot). Patients with HIV are excluded based on immuno-suppression, which may render them unable to respond to the vaccine; patients with chronic hepatitis are excluded because of concern that hepatitis could be exacerbated by the injections.
• Patients on chronic steroid therapy (or other immuno-suppressives, such as azathioprine or cyclosporin A) are excluded on the basis of potential immune suppression. Patients must have had 6 weeks of discontinuation of any steroid therapy (except that used as pre-medication for chemotherapy or contrast-enhanced studies or for acute treatment (<5 days) of intercurrent medical condition such as a gout flare) prior to enrollment.
• Pregnant and nursing women should be excluded from the protocol since this research may have unknown and harmful effects on an unborn child or on young children. If the patient is sexually active, the patient must agree to use a medically acceptable form of birth control while receiving treatment and for a period of 4 months following the last vaccination therapy. It is not known whether the treatment used in this study could affect the sperm and could potentially harm a child that may be fathered while on this study.
• Patients with acute or chronic skin disorders that will interfere with injection into the skin of the extremities or subsequent assessment of potential skin reactions will be excluded.

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: Anti-PD-1 plus DC-CIK	Biological: Anti-PD-1 plus DC-CIK; Patients will receive pembrolizumab 100mg every three weeks until disease progression, unacceptable toxicity or patient refusal. DC-CIK Immunotherapy: Mononuclear cells were collected aseptically with blood cell separator composition apheresis, and cultured DC-CIK cells for 10-14 days. Cells were infused back to the patients in 3 times via intravenous infusion .Patients will received at least 2 cycles of DC-CIK Immunotherapy along with 4 dosage of anti-PD-1 antibody treatment. If the evaluation of the treatment is partial response or stable disease, additional cycles were eligible.
Active Comparator: Anti-PD-1 alone	Biological: Anti-PD-1 alone; Patients will receive pembrolizumab 100mg every three weeks until disease progression, unacceptable toxicity or patient refusal.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression-free survival of the participants	From starting date of anti-PD-1 antibody treatment until date of until the date of first documented disease progression or date of death from any cause, whichever comes first.	12 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall survival of the participants(OS)	From starting date of anti-PD-1 antibody treatment until date of death from any cause	24 months
Assessment of Patient- Reported Outcomes Version of the Common Terminology Criteria for Adverse Events (PROCTCAE)	To assess and compare the PRO-CTCAE by patients receiving immunotherapy	24 months
Number of participants with treatment-related adverse events as assessed by CTCAE v4.0		24 months
Molecular Tumor Burden Index	Using mutation detection in ctDNA by liquid biopsy to assess tumor dynamics	24 months

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cell-free tumor DNA	To investigate the relationship of ctDNA with clincial outcomes	24 months
Tumor related antigen peptides	To investigate the relationship of tumor related antigen peptides with clincial outcomes	24 months
T cell metaboic activity	To investigate the relationship of T cell metaboic activity with clincial outcomes	24 months
Microbial bacteria	To investigate the relationship of microbial bacteria with clincial outcomes	24 months

Collaborators and Investigators

• Sponsor: Capital Medical University
• Collaborators: Duke University; Geneplus-Beijing Co. Ltd.

Study record dates

Study Major Dates

• Study Start (Actual): November 1, 2016
• Primary Completion (Actual): December 31, 2022
• Study Completion (Actual): June 1, 2023

Study Registration Dates

• First Submitted: November 27, 2017
• First Submitted That Met QC Criteria: December 1, 2017
• First Posted (Actual): December 4, 2017

Study Record Updates

• Last Update Posted (Estimated): February 7, 2024
• Last Update Submitted That Met QC Criteria: February 5, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Other Study ID Numbers: PD-1 plus DC-CIK for NSCLC

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No