DC Combined With ICIs in the Treatment of Advanced Lung Cancer Resistant to ICIs

Single-arm, Open, Prospective Clinical Study of Neoantigen-loaded Dendritic Cell Vaccine (Neo-DCVac) Combined With Immune Checkpoint Inhibitors (ICIs) in the Treatment of Advanced Lung Cancer Resistant to ICIs

This is a single-center, single-arm, prospective clinical trial to investigate the safety and efficacy of Neo-DCVac combined with ICIs in the treatment of advanced lung cancer resistant to ICIs.

Study Overview

• Status: Recruiting
• Conditions: Lung Cancer
• Intervention / Treatment: Drug: LG002

Detailed Description

The study screened patients with PD-1 immunochemotherapy in the first-line treatment regimen, and extracted tumor tissues from patients after PD-1 resistance for neoantigen prediction. During neoantigen screening and vaccine preparation, patients received a second-line regimen (docetaxel) as bridging therapy. After completion of bridging therapy and the patient 's vaccine preparation was successful, the patient started receiving the vaccine combined with ICIs. The completion of 5 vaccine injections was followed by an immunization course. Efficacy was assessed 2 weeks after the end of an immunization course, and if effective (tumor response evaluated as SD/PR/CR), the next cycle of immunotherapy was continued, with subsequent treatments administered every 3 weeks until disease progression or severe intolerance occurred or the patient requested withdrawal, whichever came first.

• Study Type: Interventional
• Enrollment (Estimated): 20
• Phase: Early Phase 1

Contacts and Locations

• Study Contact: Name: Zhengyu Ding, MD; Phone Number: 18980601957; Email: dingzhenyu@scu.edu.cn
• Study Contact Backup: Name: Qing Li, MD; Phone Number: 18702848178; Email: liqing@scu.edu.cn

Study Locations

• China
  • Si Chuan
    • Chengdu, Si Chuan, China, 610000
      • Recruiting
      • West China Hospital
      • Contact: Zhengyu Ding, MD; Phone Number: 18980601957; Email: dingzhenyu@scu.edu.cn
      • Contact: Qing Li, MD; Phone Number: 18702848178; Email: liqing@scu.edu.cn

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Aged 18-85 years.
• ECOG score was 0-2.
• Histological or cytological diagnosis confirmed non-small cell lung cancer, which was staged IIIB-IV according to AJCC version 8.
• Patients have received first-line chemotherapy combined with ICIs (PD1/PD-L1, ICIs type is not limited) and developed drug resistance.
• Normal function of major organs, that is, meeting the following criteria: a) blood routine examination (hematopoietic growth factors and blood transfusion were not used within 7 days): granulocyte count ≥ 1.5 × 109/L, platelet count ≥ 80 × 109/L, hemoglobin ≥ 80 g/L; b) biochemical examination: total bilirubin ≤ 1.5 × ULN (upper limit of normal); serum alanine aminotransferase (ALT) or serum aspartate aminotransferase (AST) ≤ 2.5 × ULN; creatinine clearance ≥ 60 mL/min (Cockcroft-Gault formula); c) coagulation function: INR or PT ≤ 1.5 × ULN (upper limit of normal), if the subject is receiving anticoagulant therapy, as long as PT is in the range proposed by anticoagulant drugs; d) urine routine examination: urine routine examination urine protein ≥ 2 +, 24-hour urine protein quantitative examination should be performed, such as quantitative urine protein ≤ 1 g/24 h.
• Female subjects of childbearing age or male subjects with sexual partners of childbearing age should take effective contraceptive measures throughout the treatment period and 6 months before and after the treatment period.
• Subjects voluntarily participate in the study and sign the informed consent form

Exclusion Criteria:

• The pathological type is mixed type, containing small cell carcinoma or other types of components.
• with the blood-borne infectious disease HIV.
• History of mental disorder, drug abuse and drug abuse.
• Any other malignancy (except completely cured cervical carcinoma in situ or basal cell or squamous cell skin cancer) within 3 years.
• Accompanied by other immune diseases, or long-term use of immunosuppressive agents or hormones.
• Any unstable systemic disease (including active uncontrolled gastrointestinal ulcers, gastric obstruction, bleeding risk or coagulopathy, active infection, for subjects with hepatitis B, anti-hepatitis B 11 virus treatment is required during study treatment, active hepatitis C subjects (HCV antibody positive and HCV- RNA levels above the lower limit of detection, grade IV hypertension, unstable angina pectoris, congestive heart failure, myocarditis, unstable cerebrovascular disease, thrombotic disease, liver, kidney, uncontrolled metabolic disease or unhealed fractures, wounds as judged by the surgeon).
• Presence of active central nervous system (CNS) metastases; subjects with previously treated brain metastases (e.g., surgery, radiotherapy, hormone therapy) are allowed if clinically stable for at least two weeks after treatment from the first dose of study drug and corticosteroids are discontinued 7 days before study drug administration; untreated, asymptomatic subjects with brain metastases (i.e., no neurological symptoms, no need for corticosteroids, no significant edema around the brain metastases) can be enrolled.
• Any anti-tumor therapy including chemotherapy, radiotherapy, and targeted therapy within 3 weeks prior to the first dose of study drug.
• Presence of pleural effusion, pericardial effusion, or ascites with clinical symptoms or requiring drainage.
• Previous use of anti-tumor vaccines, live vaccines within 30 days.
• Patients are difficult to communicate or to follow up for a long time. Pregnant or lactating women.
• Current or planned participation in other clinical trials.
• Dr. finds other unsuitable situations

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: (Neo-DCVac) combined with immune checkpoint inhibitors (ICIs); DC cell injection ,1.5 × 10 7/time, subcutaneous multi-point injection in axilla and groin or lymph node injection guided by color Doppler ultrasound in axilla and groin, continuous injection at 0W, 1W, 3W, 5W and 7W for five times as the first immunization cycle. Tumor response was evaluated 2 weeks after the completion of the first immunotherapy cycle, and treatment was continued if the response was evaluated as effective (SD/PR/CR), and every 3 weeks until disease progression or intolerable toxicity or active withdrawal of the patient, whichever came first.ICIs are PD1/PD-L1 inhibitors and continue to be pre-enrollment ICIs of any brand

Drug: LG002; Neo-DCVac combined with ICIs in the treatment of advanced lung cancer resistant to ICIs.; Other Names: ICIs

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The safety of Neo-DCVac combined with ICIs.	This study will collected any adverse medical events that occurred during the study drug treatment, and the treatment-related adverse events as assessed by" CTCAE v5.0".	2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The efficacy of Neo-DCVac combined with ICIs.	Using the revisit1.1 tumor evaluation criteria for efficacy evaluation, evaluate disease progression free survival (PFS) .	2 years
The efficacy of Neo-DCVac combined with ICIs.	Using the revisit1.1 tumor evaluation criteria for efficacy evaluation, evaluate disease objective response rate (ORR).	2 years

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Synergistic anti-tumor mechanism.	The immune response of subjects was assessed by peripheral blood cell flow cytometry within 2 weeks after the initial immunotherapy and every 3 months during the immunomaintenance treatment.	2 years

Collaborators and Investigators

• Sponsor: Zhen-Yu Ding
• Investigators: Study Chair: Qing Li, MD, West China Hospital

Study record dates

Study Major Dates

• Study Start (Actual): September 27, 2023
• Primary Completion (Estimated): September 30, 2024
• Study Completion (Estimated): October 31, 2026

Study Registration Dates

• First Submitted: December 28, 2023
• First Submitted That Met QC Criteria: March 19, 2024
• First Posted (Actual): March 26, 2024

Study Record Updates

• Last Update Posted (Actual): March 26, 2024
• Last Update Submitted That Met QC Criteria: March 19, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Keywords: Criteria for inclusion
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Neoplasms; Lung Diseases; Neoplasms by Site; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Neoplasms
• Other Study ID Numbers: TSLG-001

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