The Effect of Combined Cryotherapy and Immunotherapy on Systemic T Cell Changes and Clinical Outcomes in Metastatic Non-small Cell Lung Cancer (LUCACRIMUNO)

Lithuanian University of Health Sciences

Status: Enrolling

Conditions: Lung Cancer Stage IV

Treatments: Procedure: Bronchoscopic cryotherapy; Drug: Pembrolizumab; Drug: Platinum based chemotherapy

Study type: Interventional

Funder types: Other

Identifiers

NCT06000358

LUCACRIMUNO-001

Details and patient eligibility

About

Lung cancer remains one of the most commonly diagnosed oncological diseases worldwide and the first in terms of mortality. Although immune checkpoint inhibitors form the backbone of current metastatic non-small cell lung cancer treatments, there is still no ideal predictive marker for its efficacy and patients still achieve suboptimal results in overall response and survival. While immune checkpoint inhibitors are known to shift systemic anti-tumor immune response from suppression to stimulation in some patients, the investigators hypothesize that this effect can be further enhanced by cryotherapy, especially in "cold" tumors. If proven successful, cryotherapy in combination with immunotherapy, could potentiate a more powerful immune response compared to systemic therapy alone, improve overall response rate, patients' survival without disease progression, and overall survival. The investigators, therefore, aim to use combined local tumor cryotherapy, combined with immune checkpoint inhibitor therapy to induce and evaluate systemic anti-tumor T lymphocyte response and achieve improved non-small cell lung cancer patient outcomes than with immunotherapy alone.

Enrollment: 120 estimated patients

Sex: All

Ages: 18 to 99 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Patients with Eastern Cooperative Oncology Group (ECOG) performance score 0 - 1;
• Patients with histologically confirmed metastatic non-small cell lung cancer and PD-L1 expression on tumor cells was evaluated;
• CT examination shows measurable tumor formations according to the RECIST 1.1 criteria;
• Primary lung tumor or metastasis accessible to flexible bronchoscopy;
• Patients may have received surgery, adjuvant or neoadjuvant chemotherapy prior to the study if it was completed at least 12 months before relapse;
• Patients informed about the purpose and course of the study and provided a written consent to participate.

Exclusion criteria

• Patients who refused to participate in the clinical trial and did not sign the informed consent form;
• Men and women under the age of 18, pregnant women;
• Patients belonging to a vulnerable social group;
• High risk of general anesthesia, defined as American Society of Anesthesiologists (ASA) class 4 - 6;
• Documented allergy to medications used during general and local anesthesia, systemic cancer treatment;
• Patients previously treated with immune checkpoint inhibitors;
• EGFR mutations or ALK translocations have been identified in patients;
• Patients with previously diagnosed autoimmune diseases, active viral hepatitis, uncontrolled human immunodeficiency virus (HIV) infection or untreated tuberculosis;
• Patients treated with immunosuppressive drugs, systemic corticosteroids, with equivalent doses of prednisolone exceeding 10 mg/day;
• Patients with an increased risk of bleeding during an interventional procedure;
• Acute untreated conditions that would make it impossible to perform an interventional lung procedure.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

---

120 participants in 4 patient groups

Cryotherapy and Pembrolizumab monotherapy;

Active Comparator group

Description:

Patients with metastatic non-small cell lung cancer, who are eligible for first-line pembrolizumab monotherapy (PD-L1 expression equal to or greater than 50%, no EGFR mutations or ALK translocations). Bronchoscopic cryotherapy procedure is performed before the start of systemic treatment.

Treatment:

Procedure: Bronchoscopic cryotherapy

Drug: Pembrolizumab

Cryotherapy and Pembrolizumab with platinum-based chemotherapy;

Active Comparator group

Description:

Patients with metastatic non-small cell lung cancer, who are eligible for first-line pembrolizumab and platinum-based chemotherapy (PD-L1 expression less than 50%, no EGFR mutations or ALK translocations). Bronchoscopic cryotherapy procedure is performed before the start of systemic treatment.

Treatment:

Procedure: Bronchoscopic cryotherapy

Drug: Pembrolizumab

Drug: Platinum based chemotherapy

Pembrolizumab monotherapy;

Active Comparator group

Description:

Patients with metastatic non-small cell lung cancer, who are eligible for first-line pembrolizumab monotherapy (PD-L1 expression equal to or greater than 50%, no EGFR mutations or ALK translocations).

Treatment:

Drug: Pembrolizumab

Pembrolizumab with platinum-based chemotherapy;

Active Comparator group

Description:

Patients with metastatic non-small cell lung cancer, who are eligible for first-line pembrolizumab and platinum-based chemotherapy (PD-L1 expression less than 50%, no EGFR mutations or ALK translocations).

Treatment:

Drug: Pembrolizumab

Drug: Platinum based chemotherapy