Neoadjuvant Nivolumab Combination Treatment in Resectable Non-small Cell Lung Cancer Patients: Defining Optimal Combinations and Determinants of Immunological Response
Overview
- Phase
- Phase 2
- Intervention
- Nivolumab 10 MG/ML Intravenous Solution
- Conditions
- NSCLC Stage II
- Sponsor
- University Hospital, Essen
- Enrollment
- 90
- Locations
- 4
- Primary Endpoint
- Feasibility of four weeks of preoperative immunotherapy with Nivolumab, Nivolumab plus Relatlimab (80 mg), and Nivolumab plus Relatlimab (240 mg)
- Status
- Recruiting
- Last Updated
- last year
Overview
Brief Summary
The primary objective of this study is to determine the feasibility of four weeks of preoperative immunotherapy with Nivolumab, and Nivolumab plus Relatlimab in patients with early stage or locally advanced non-small cell lung cancer eligible for curative resection.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Patients with histologically confirmed non-small cell lung cancer (NSCLC) eligible for anatomic resection (Clinical stages I B, II and selected stage III A)
- •Eastern Cooperative Oncology Group (ECOG) ≤ 1
- •Sufficient pulmonary function to undergo curative lung cancer surgery
- •Adequate hematological, hepatic and renal function parameters:
- •Sufficient cardiac left ventricular defined as left ventricular ejection fraction (LVEF) ≥ 50% documented either by echocardiography or multigated acquisition scan (MUGA)
- •Patient able and willing to provide written informed consent and to comply with the study protocol and with the planned surgical procedures
Exclusion Criteria
- •Active or history of autoimmune disease or immune deficiency
- •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
- •Subjects who have undergone organ transplant or allogeneic stem cell transplantation
- •Uncontrolled or significant cardiovascular disease
- •Patients with active neurological disease
- •Active malignancy or a prior malignancy within the past 3 years
- •Receipt of live attenuated vaccine within 30 days prior to the first dose of study medication
- •Peripheral polyneuropathy NCI CTCAE Grade ≥ 2
- •History of gastric perforation or fistulae in past 6 months
- •Serious or non-healing wound, ulcer, or bone fracture within 28 days prior to enrollment.
Arms & Interventions
Nivolumab
Nivolumab 2 cycles, every two weeks (q2w) o Nivolumab 240 mg i.v. over 30 min
Intervention: Nivolumab 10 MG/ML Intravenous Solution
Nivolumab/Relatlimab (80 mg)
Nivolumab/Relatlimab (80 mg) 2 cycles, every two weeks (q2w) * Nivolumab 240 mg i.v. over 30 min * Relatlimab 80 mg i.v. over 30 min (within 30 min of nivolumab)
Intervention: Nivolumab 10 MG/ML Intravenous Solution
Nivolumab/Relatlimab (80 mg)
Nivolumab/Relatlimab (80 mg) 2 cycles, every two weeks (q2w) * Nivolumab 240 mg i.v. over 30 min * Relatlimab 80 mg i.v. over 30 min (within 30 min of nivolumab)
Intervention: Relatlimab 10 MG/ML Intravenous Solution
Nivolumab/Relatlimab (240 mg)
Nivolumab/Relatlimab (240 mg) 2 cycles, every two weeks (q2w) * Nivolumab 240 mg i.v. over 30 min * Relatlimab 240 mg i.v. over 30 min (within 30 min of nivolumab)
Intervention: Nivolumab 10 MG/ML Intravenous Solution
Nivolumab/Relatlimab (240 mg)
Nivolumab/Relatlimab (240 mg) 2 cycles, every two weeks (q2w) * Nivolumab 240 mg i.v. over 30 min * Relatlimab 240 mg i.v. over 30 min (within 30 min of nivolumab)
Intervention: Relatlimab 10 MG/ML Intravenous Solution
Outcomes
Primary Outcomes
Feasibility of four weeks of preoperative immunotherapy with Nivolumab, Nivolumab plus Relatlimab (80 mg), and Nivolumab plus Relatlimab (240 mg)
Time Frame: Within 43 days after first study medication
Secondary Outcomes
- Objective radiological response rate(After 3, 6, 9 and 12 months post-surgery)
- Disease-free survival rate at 12 months(12 months)
- Overall survival rate at 12 months(12 months)
- Estimation of curative (R0) resection rate(Within 43 days after first study medication (day of surgery))
- Morbidity(within 90 days after surgery)
- Mortality(within 90 days after surgery)
- Estimation of pathological tumor response rate(Within 43 days after first study medication (day of surgery))