Neoadjuvant Intra-tumor Double Immunotherapy for Lung Cancer.

NCT06492421 | Recruiting Phase 2 FDA Drug

• 1 other identifier: ZZ-IT-ICIs-LC-Neoadjuvant-028
• Study Type: interventional
• Target: 90
• Locations: 1 country
• Sites: 1

Brief Summary

This phase II trial studies how well intra-tumor injection of double checkpoint inhibitors work when given alone and in combination with chemotherapy or/and bevacizumab in treating patients with previously untreated stage I-IIIA non-small cell lung cancer. Immunotherapy with monoclonal antibodies, such as ipilimumab, pembrolizumab or durvalumab, may help the body's immune system attack the tumor, and may interfere with the ability of tumor cells to grow and spread. Drugs used in interventional radiological chemotherapy, such as idabubicin, can directly kill the cancer cell and release tumor antigens to activate DC function in situ. Giving intra-tumor injection of checkpoints inhibitors with or without chemotherapy and/or bevecizumab may work better than in vein infusion of the drugs in treating patients with non-small cell lung cancer.

Conditions

Lung Cancer; Surgery; Non-small Cell Lung Cancer

Keywords

NSCLC; Intra-tumor injection; Neoadjuvant therapy; Double immunotherapy; Interventional radiology; Bevacizumab

Outcome Measures

Primary Outcomes (2)

• pCR rate for the study groups

  Pathologic complete response (pCR) is defined as after neoadjuvant therapy, the surgical specimen can not find any residual cancer cells.

  Six months

• mPR rate for the study groups

  Major pathologic response (MPR) is defined as pathological less than 10% survival cancer cells after tumor resection.

  Six months

Secondary Outcomes (3)

• Toxicity of the study groups

  Six months

• Response rates to neoadjuvant treatment

  Six years

• Overall survival

  Six years

Study Arms (3)

Group 1: IT injection of double ICIs

EXPERIMENTAL

Neoadjuvant therapy: intra-tumor injection of double ICIs only.

Drug: ipilimumab, pembrolizumab, durvalumab, idarubicin, bevacizumab

Group 2: IT injection of double ICIs and chemodrug

EXPERIMENTAL

Neoadjuvant therapy: intra-tumor injection of double ICIs and chemodrug.

Drug: ipilimumab, pembrolizumab, durvalumab, idarubicin, bevacizumab

Group 3: IT injection of double ICIs and chemodrug plus bevacizumab

EXPERIMENTAL

Neoadjuvant therapy: intra-tumor injection of double ICIs and chemodrug plus bevacizumab.

Drug: ipilimumab, pembrolizumab, durvalumab, idarubicin, bevacizumab

Interventions

ipilimumab, pembrolizumab, durvalumab, idarubicin, bevacizumab DRUG

This study has 3 subgroups: Arm 1. Ipilimumab +pembrolizumab or Ipilimumab +durvalumab is administrated with a total dose of 1-2mg/kg via intra-tumor fine needle injection in 10 min, every 3 weeks, total 3-4 times. Arm 2. Ipilimumab +pembrolizumab or Ipilimumab +durvalumab combined with idarubicin is administrated via intra-tumor fine needle injection in 15 min, every 3 weeks, total 3-4 times. Arm 3. Ipilimumab +pembrolizumab or Ipilimumab +durvalumab combined with idarubicin plus bevacizumab is administrated via intra-tumor fine needle injection in 20 min, every 3 weeks, total 3-4 times.

Also known as: Other ICIs

Group 1: IT injection of double ICIs; Group 2: IT injection of double ICIs and chemodrug; Group 3: IT injection of double ICIs and chemodrug plus bevacizumab

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Histologically or cytologically confirmed previously untreated non-small cell lung cancer. If a diagnostic biopsy is available, a pre-treatment biopsy is not required. Patients with a suspected lung cancer are eligible, but pathology must be confirmed prior to initiating treatment on study.
• Patients with stage IIIA must not have more than one mediastinal lymph node station involved by tumor.
• All patients must have lymph node evaluation of contralateral stations 2 and/or 4 to exclude N3 disease.
• The patient must be a suitable candidate for surgery, in the opinion of the treating physician.
• Signed and dated written informed consent must be provided by the patient prior to admission to the study in accordance with International Conference on Harmonization-Good Clinical Practice (ICH-GCP) guidelines and to the local legislation.
• Eastern Cooperative Oncology Group (ECOG) performance status score 0-1.
• Absolute neutrophil count (ANC) \>= 1.5 x 10\^9/L; Hemoglobin \>= 8.0 g/dL; Platelets \>= 100 x 10\^9/L; Total bilirubin =\< 1.5 x upper limit of normal (ULN) (except subjects with Gilbert syndrome who can have total bilirubin \< 3.0 mg/dL); Creatinine =\< 1.5 x ULN or calculated creatinine clearance \>= 50 mL/min using Cockcroft-Gault formula for creatinine clearance calculation OR 24-hour urine creatinine clearance \>= 50 mL/min.

You may not qualify if:

• Prior systemic therapy or radiation therapy for treatment of the current lung cancer.
• Currently receiving cancer therapy (chemotherapy, radiation therapy, immunotherapy, or biologic therapy) or investigational anti-cancer drug.
• Pregnant or lactating female.
• Unwillingness or inability to follow the procedures required in the protocol.
• Patients with pre-existing sensorineural hearing impairment/loss or newly diagnosed as documented by an audiology assessment performed prior to study enrollment may not be eligible for cisplatin and may be dispositioned to carboplatin, as determined by the treating physician.
• Patients with a history of severe hypersensitivity reaction to taxotere and or polysorbate 80 must be excluded.
• Any serious or uncontrolled medical disorder that, in the opinion of the investigator, may increase the risk associated with study participation or study drug administration, impair the ability of the subject to receive protocol therapy, or interfere with the interpretation of study results.
• Subjects with active, known or suspected autoimmune disease. Subjects with vitiligo, type I diabetes mellitus, residual hypothyroidism due to autoimmune condition only requiring hormone replacement, psoriasis not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger are permitted to enroll.
• Subjects with a condition requiring systemic treatment with either corticosteroids (\> 10 mg daily prednisone equivalents) or other immunosuppressive medications within 14 days of study drug administration. Inhaled or topical steroids and adrenal replacement doses \> 10 mg daily prednisone equivalents are permitted in the absence of active autoimmune disease. Subjects are permitted to use topical, ocular, intra-articular, intranasal, and inhalational corticosteroids (with minimal systemic absorption). Physiologic replacement doses of systemic corticosteroids are permitted, even if \> 10 mg/day prednisone equivalents. A brief course of corticosteroids for prophylaxis (eg, contrast dye allergy) or for treatment of non-autoimmune conditions (eg, delayed-type hypersensitivity reaction caused by contact allergen) is permitted.
• Prior treatment with an anti-PD-1, anti-PD-L1 or anti-CTLA-4 antibody.
• Known positive test for hepatitis B virus surface antigen (HBV sAg) or hepatitis C virus ribonucleic acid indicating acute or chronic infection.
• Known history of testing positive for human immunodeficiency virus or known acquired immunodeficiency syndrome.
• History of severe hypersensitivity reaction to any monoclonal antibody and/or to study drug components.
• Serious illness or concomitant non-oncological disease such as neurologic, psychiatric, infectious disease or laboratory abnormality that may increase the risk associated with study participation or study drug administration and in the judgment of the investigator would make the patient inappropriate for entry into the study.
• Psychological, familial, sociological or geographical factors potentially hampering compliance with the study protocol and follow-up schedule.

Sponsors & Collaborators

• Second Affiliated Hospital of Guangzhou Medical University: lead

Study Sites (1)

The Second Affiliated Hospital of Guangzhou Medical University

Guanzhou, Guangdong, 51260, China

RECRUITING

MeSH Terms

Conditions

Lung Neoplasms; Carcinoma, Non-Small-Cell Lung

Interventions

Ipilimumab; pembrolizumab; durvalumab; Idarubicin; Bevacizumab

Condition Hierarchy (Ancestors)

Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases; Carcinoma, Bronchogenic; Bronchial Neoplasms

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Daunorubicin; Anthracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Polycyclic Compounds; Aminoglycosides; Glycosides; Carbohydrates

Study Officials

• Zhenfeng Zhang, MD, PhD

  Second Affiliated Hospital of Guangzhou Medical University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Zhenfeng Zhang, MD, PhD

CONTACT

+862039195966; zhangzhf@gzhmu.edu.cn

Bingjia He, MD

CONTACT

+862039195965; 464677938@qq.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 2, 2024
• First Posted: July 9, 2024
• Study Start: July 1, 2024
• Primary Completion (Estimated): December 30, 2028
• Study Completion (Estimated): December 30, 2035
• Last Updated: July 9, 2024

Record last verified: 2024-07

Locations

CN (1)