Neoadjuvant Nivolumab Combination Treatment in Resectable Non-small Cell Lung Cancer Patients

Study Overview
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Brief Summary
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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.

Official Title
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Neoadjuvant Nivolumab Combination Treatment in Resectable Non-small Cell Lung Cancer Patients: Defining Optimal Combinations and Determinants of Immunological Response

Conditions
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NSCLC Stage II, NSCLC, Stage IIIA, NSCLC, Stage I

Intervention / Treatment
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* Drug: Nivolumab 10 MG/ML Intravenous Solution
* Drug: Relatlimab 10 MG/ML Intravenous Solution


Participation Criteria
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Eligibility Criteria
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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. The patient has undergone major surgery within 28 days prior to enrollment except staging mediastinoscopy, diagnostic Video Assisted Thoracoscopic Surgery (VATS) or implantation of a venous port-system. Any other concurrent preoperative antineoplastic treatment including irradiation Pregnant/Breastfeeding women Subjects with history of severe toxicity or life-threatening toxicity (grade 3 or 4) related to prior immune therapy Prior treatment with Lymphocyte-activation gene 3 (LAG-3) targeting Agent Previous treatment with Nivolumab or Relatlimab

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Nivolumab<br>Nivolumab 2 cycles, every two weeks (q2w) o Nivolumab 240 mg i.v. over 30 min | Drug: Nivolumab 10 MG/ML Intravenous Solution<br>* Neoadjuvant 2 cycles, every two weeks (q2w) Nivolumab 240 mg i.v. over 30 min<br>|
| Experimental: Nivolumab/Relatlimab (80 mg)<br>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) | Drug: Nivolumab 10 MG/ML Intravenous Solution<br>* Neoadjuvant 2 cycles, every two weeks (q2w) Nivolumab 240 mg i.v. over 30 min<br>Drug: Relatlimab 10 MG/ML Intravenous Solution<br>* Neoadjuvant 2 cycles, every two weeks (q2w) Relatlimab 80 mg i.v. over 30 min<br>|
| Experimental: Nivolumab/Relatlimab (240 mg)<br>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) | Drug: Nivolumab 10 MG/ML Intravenous Solution<br>* Neoadjuvant 2 cycles, every two weeks (q2w) Nivolumab 240 mg i.v. over 30 min<br>Drug: Relatlimab 10 MG/ML Intravenous Solution<br>* Neoadjuvant 2 cycles, every two weeks (q2w) Relatlimab 80 mg i.v. over 30 min<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Feasibility of four weeks of preoperative immunotherapy with Nivolumab, Nivolumab plus Relatlimab (80 mg), and Nivolumab plus Relatlimab (240 mg) |  | Within 43 days after first study medication | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Estimation of pathological tumor response rate |  | Within 43 days after first study medication (day of surgery) | 
| Estimation of curative (R0) resection rate |  | Within 43 days after first study medication (day of surgery) | 
| Objective radiological response rate | Objective radiological response rate per Response Evaluation Criteria In Solid Tumors (RECIST) version 1.1 | After 3, 6, 9 and 12 months post-surgery | 
| Disease-free survival rate at 12 months | Assessment of disease-free survival rate at 12 months per Response Evaluation Criteria In Solid Tumors (RECIST) version 1.1 | 12 months | 
| Overall survival rate at 12 months |  | 12 months | 
| Morbidity | Estimation of morbidity within 90 days after surgery | within 90 days after surgery | 
| Mortality | Estimation of mortality within 90 days after surgery | within 90 days after surgery |