Anti-PD-1 Antibody Combined With Autologous DC and NK Cells in the Treatment of Digestive Carcinoma

NCT05461235 | Unknown Phase 2 DMC

• 1 other identifier: COMBINE
• Study Type: interventional
• Target: 1
• Locations: 0 countries
• Sites: N/A

Brief Summary

This is a prospective, open, single-arm Phase II clinical study to evaluate the efficacy and safety of anti-PD-1 antibody combined with autologous DC and NK cells in the treatment of digestive carcinoma.

Conditions

PD-1 Antibody; DC-Cell; NK-Cell; Gastrointestinal Tumours

Outcome Measures

Primary Outcomes (1)

• Progression-free Survival (PFS)

  PFS, defined as the time from randomization to the first occurrence of disease progression as determined by the investigator with use of RECIST v1.1 or death from any cause, whichever occurs first.

  one year

Secondary Outcomes (3)

• Objective Response Rate (ORR)

  one year

• Disease Control Rate (DCR)

  one year

• Overall Survival (OS)

  two years

Study Arms (1)

Anti-PD-1 antibody combined with autologous DC and NK cells

EXPERIMENTAL

Anti-PD-1 antibodies (one of six options) 1. Pembrolizumab: 2 mg/kg or 200 mg by intravenous infusion every 3 weeks 2. Nivolumab:3 mg/kg or 240 mg by intravenous infusion every 2 weeks 3. Sintilimab: 200 mg by intravenous infusion every 3 weeks 4. Toripalimab: 3 mg/kg or 240 mg by intravenous infusion every 2 weeks 5. Camrelizumab: 200 mg by intravenous infusion every 2 or 3 weeks, or 3 mg/kg by intravenous infusion every 3 weeks 6. Tislelilzumab: 200mg by intravenous infusion every 3 weeks. DC, NK cells. 50ml of peripheral blood is collected 1 day before the dosing cycle for in vitro isolation and expansion of DC and NK cells; the first infusion of DC and NK cells (not less than 1x10\^6 cells/Kg) is completed on day 14.

Drug: Pembrolizumab; Drug: Nivolumab; Drug: Sintilimab; Drug: Toripalimab; Drug: Camrelizumab; Drug: Tislelizumab; Biological: NK-Cell or DC-Cell

Interventions

Pembrolizumab DRUG

2mg/kg or 200mg,iv,q3w

Also known as: Keytruda

Anti-PD-1 antibody combined with autologous DC and NK cells

Nivolumab DRUG

3mg/kg or 240mg,iv,q2w

Also known as: Opdivo

Anti-PD-1 antibody combined with autologous DC and NK cells

Sintilimab DRUG

200mg,iv,q3w

Also known as: Daboshu

Anti-PD-1 antibody combined with autologous DC and NK cells

Toripalimab DRUG

3mg/kg or 240mg,iv,q2w

Also known as: Tuoyi

Anti-PD-1 antibody combined with autologous DC and NK cells

Camrelizumab DRUG

200mg,iv,q2w or q3w;3mg/kg,iv,q3w

Also known as: Airuika

Anti-PD-1 antibody combined with autologous DC and NK cells

Tislelizumab DRUG

200mg,iv,q3w

Also known as: Baizean

Anti-PD-1 antibody combined with autologous DC and NK cells

NK-Cell or DC-Cell BIOLOGICAL

50ml of peripheral blood was collected 1 day before the dosing cycle for in vitro isolation and amplification of DC and NK cells; the first transfusion of DC and NK cells (not less than 1x10\^6 cells/Kg) was completed on day 14.

Anti-PD-1 antibody combined with autologous DC and NK cells

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• age: 18-70 years, of either sex 2. pathologically confirmed locally advanced or metastatic gastrointestinal tumour (stage III or IV according to AJCC 8th edition staging) with at least one measurable lesion (meeting RECIST 1.1 criteria) 3. ECOG PS: 0-1 points 4. have adequate organ and bone marrow function, i.e. meet the following criteria.
• Routine blood test criteria to be met.
• HB ≥ 90g/L.
• ANC ≥1.5×109/L.
• PLT ≥90 x 109/L.
• Absolute value of lymphocytes + monocytes \>2.0\*10\^9/L.
• Biochemical tests are required to meet the following criteria.
• Total bilirubin ≤ 1.5 times the upper limit of normal (ULN).
• ALT and AST ≤ 2.5ULN.
• serum Cr ≤ 1 ULN and endogenous creatinine clearance \> 60 ml/min (Cockcroft-Gault formula).
• \. international normalised ratio (INR) ≤ 1.5 and partial thromboplastin time (PPT or APTT) ≤ 1.5 ULN within 7 days prior to enrolment 6. expected survival of ≥ 3 months. 7. signed informed consent form (ICF) prior to study enrolment. 8 Women of childbearing potential must have had a pregnancy test (serum or urine) within 7 days prior to enrolment and have a negative result. Female patients of childbearing age or male patients whose sexual partners are women of childbearing age are required to use effective contraception throughout the treatment period and for 6 months after the last dose.

You may not qualify if:

• \. known hypersensitivity to any of the components of the anti-PD-1 antibody formulation; or previous severe allergic reactions to other monoclonal antibodies.
• \. diagnosis of other malignancies, excluding radically treated basal cell carcinoma of the skin, squamous cell carcinoma of the skin and/or radically resected carcinoma in situ, within 5 years prior to the first dose 3. Subjects who have been treated with an antitumour vaccine or other antitumour agents with immunostimulatory effects (interferon, interleukin, thymidine, immune cell therapy, etc.) within 1 month prior to the first dose.
• \. CNS metastases with symptoms. Subjects may be enrolled in the study if their CNS metastases have been treated, e.g., clinical stability (MRI detection) has been maintained for at least 4 weeks, and the subject's clinical symptoms, such as neurological symptoms, are able to return to baseline levels at least 2 weeks prior to the first dose (except for residual signs or symptoms related to CNS treatment). In addition, subjects receiving stable or tapered doses of ≤10 mg/day of prednisone (or equivalent) for at least 2 weeks for clinical symptoms associated with treatment with corticosteroids are not eligible for enrollment in the study, otherwise they cannot be enrolled.
• \. Acute or chronic active hepatitis B (defined as positive HBsAg for hepatitis B virus surface antigen at screening) or hepatitis C infection. Patients with previous hepatitis B virus (HBV) infection or cured HBV infection (defined as hepatitis B core (HBc) antibody positive and HBsAg negative) who are negative for HBV DNA only may be enrolled in this study. HBV DNA testing must be performed on this group of patients prior to enrolment. Patients who are positive for hepatitis C virus (HCV) antibodies and negative for HCV RNA only by polymerase chain reaction may be enrolled in the study. Patients who are antigen-positive but have DNA/RNA copy numbers within the permissible range should be considered for antiviral treatment if enrolled in this study and DNA/RNA levels should be monitored in real time for the duration of the study.
• \. previous and current history of pulmonary fibrosis, interstitial pneumonia, pneumoconiosis, drug-related pneumonia, severely impaired lung function and other lung diseases.
• \. active tuberculosis (TB), on anti-TB treatment or who have received anti-TB treatment within 1 year prior to the first dose 8. Human immunodeficiency virus (HIV) infected (HIV-positive), known syphilis infection 9. Patients who are considered to be at high medical risk due to severe, uncontrollable disease, non-metastatic systemic disease or having an active, uncontrollable infection. Some examples include, but not all, uncontrolled ventricular arrhythmias, recent (within 3 months) myocardial infarction, uncontrollable grand mal seizures, unstable spinal cord compression, superior vena cava syndrome, HRCT suggestive of extensive bilateral interstitial lung disease or any mental illness that may prevent informed consent from being obtained 10. active autoimmune disease requiring systemic therapy (e.g. use of disease-relieving drugs, corticosteroids or immunosuppressants) that occurred within 2 years prior to the first dose Alternative therapies (e.g. thyroxine, insulin or physiological corticosteroids for adrenal or pituitary insufficiency, etc.) are permitted Known history of primary immunodeficiency. Patients with positive autoimmune antibodies only need to confirm the presence of autoimmune disease at the discretion of the investigator.
• \. Use of immunosuppressive drugs within 4 weeks prior to first dose, excluding topical glucocorticoids by nasal spray, inhalation or other routes or physiological doses of systemic glucocorticoids (i.e. not more than 10 mg/day prednisone or equivalent doses of other glucocorticoids), temporary use of glucocorticoids for the treatment of symptoms of dyspnea in conditions such as asthma, chronic obstructive pulmonary disease is permitted.

Sponsors & Collaborators

• China Medical University, China: lead

MeSH Terms

Interventions

pembrolizumab; Nivolumab; sintilimab; toripalimab; camrelizumab; tislelizumab

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Yunpeng Liu, PhD

  First Hospital of China Medical University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Yunpeng Liu, PhD

CONTACT

86-24-83282312; cmu_trial@163.com

Ling Xu, PhD

CONTACT

cmuxuling@163.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Director of Department of Medical Oncology

Model Details: Single Group Assignment

Study Record Dates

• First Submitted: July 14, 2022
• First Posted: July 18, 2022
• Study Start: July 15, 2022
• Primary Completion: July 15, 2025
• Study Completion: December 1, 2025
• Last Updated: July 18, 2022

Record last verified: 2022-07

Data Sharing

• IPD Sharing: Will not share