Neoadjuvant double immunotherapy for lung cancer treatment

Phase II Study of Neoadjuvant CT-Guided Intra-tumor Double Checkpoint Blockades for Untreated Stage I-IIIA Non-Small Cell Lung Cancers Amenable for Surgical Resection

This study is testing a new way to treat early-stage lung cancer by using a combination of two immune therapies injected directly into the tumor to see if it helps patients feel better and live longer.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 90 (estimated)
• Ages: 18 Years to 75 Years
• Sex: All
• Sponsor: Second Affiliated Hospital of Guangzhou Medical University (Academic / other)
• Drugs / interventions: chemotherapy, immunotherapy, radiation, prednisone, bevacizumab, ipilimumab, pembrolizumab, durvalumab, bevecizumab
• Locations: 1 site (Guanzhou, Guangdong)
• Trial ID: NCT06492421 on ClinicalTrials.gov

What this trial studies

This phase II trial investigates the effectiveness of intra-tumor injections of double checkpoint inhibitors, specifically ipilimumab combined with either pembrolizumab or durvalumab, in treating patients with previously untreated stage I-IIIA non-small cell lung cancer (NSCLC). The study aims to assess the safety and survival benefits of this neoadjuvant therapy, which may enhance local drug concentration and reduce systemic side effects compared to traditional intravenous administration. Additionally, the trial explores the potential benefits of combining these immunotherapies with chemotherapy or bevacizumab. The goal is to improve patient outcomes by leveraging the body's immune response against the tumor.

Who should consider this trial

Good fit: Ideal candidates include patients with histologically confirmed, previously untreated stage I-IIIA non-small cell lung cancer who are suitable for surgery.

Not a fit: Patients with advanced stage NSCLC or those not suitable for surgery may not benefit from this study.

Why it matters

Potential benefit: If successful, this approach could significantly improve treatment outcomes for patients with non-small cell lung cancer.

How similar studies have performed: While the use of checkpoint inhibitors has been successful in various cancers, this specific approach of intra-tumor delivery combined with double immunotherapy is novel and has not been extensively tested.

Eligibility criteria

Inclusion Criteria:

1. 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.
2. Patients with stage IIIA must not have more than one mediastinal lymph node station involved by tumor.
3. All patients must have lymph node evaluation of contralateral stations 2 and/or 4 to exclude N3 disease.
4. The patient must be a suitable candidate for surgery, in the opinion of the treating physician.
5. 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.
6. Eastern Cooperative Oncology Group (ECOG) performance status score 0-1.
7. 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.

Exclusion Criteria:

1. Prior systemic therapy or radiation therapy for treatment of the current lung cancer.
2. Currently receiving cancer therapy (chemotherapy, radiation therapy, immunotherapy, or biologic therapy) or investigational anti-cancer drug.
3. Pregnant or lactating female.
4. Unwillingness or inability to follow the procedures required in the protocol.
5. 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.
6. Patients with a history of severe hypersensitivity reaction to taxotere and or polysorbate 80 must be excluded.
7. 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.
8. 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.
9. 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.
10. Prior treatment with an anti-PD-1, anti-PD-L1 or anti-CTLA-4 antibody.
11. Known positive test for hepatitis B virus surface antigen (HBV sAg) or hepatitis C virus ribonucleic acid indicating acute or chronic infection.
12. Known history of testing positive for human immunodeficiency virus or known acquired immunodeficiency syndrome.
13. History of severe hypersensitivity reaction to any monoclonal antibody and/or to study drug components.
14. 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.
15. Psychological, familial, sociological or geographical factors potentially hampering compliance with the study protocol and follow-up schedule.
16. Allergic to contrast agent.
17. Any agents which could affect the absorption or pharmacokinetics of the study drugs.
18. Other conditions that investigator decides not suitable for the trial.

Where this trial is running

Guanzhou, Guangdong

• The Second Affiliated Hospital of Guangzhou Medical University — Guanzhou, Guangdong, China (Recruiting)

Study contacts

• Principal investigator: Zhenfeng Zhang, MD, PhD — Second Affiliated Hospital of Guangzhou Medical University
• Study coordinator: Zhenfeng Zhang, MD, PhD

Conditions Lung Cancer; Surgery; Non-small Cell Lung Cancer; NSCLC; Intra-tumor injection; Neoadjuvant therapy; Double immunotherapy; Interventional radiology