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

Phase 2

Recruiting

• Conditions: NSCLC Stage II; NSCLC, Stage IIIA; NSCLC, Stage I
• Interventions: Drug: Nivolumab 10 MG/ML Intravenous Solution; Drug: Relatlimab 10 MG/ML Intravenous Solution

• Registration Number: NCT04205552
• Lead Sponsor: University Hospital, Essen

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2019-12-16
• Study First Submitted QC: 2019-12-17
• Study First Posted: 2019-12-19
• Study Start: 2020-03-04
• Status Verified: 2024-05
• Last Update Submitted: 2024-05-07
• Last Update Posted: 2024-05-09
• Primary Completion: 2025-03
• Study Completion: 2025-06

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 90

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Nivolumab	Nivolumab 10 MG/ML Intravenous Solution	Nivolumab 2 cycles, every two weeks (q2w) o Nivolumab 240 mg i.v. over 30 min
Nivolumab/Relatlimab (80 mg)	Nivolumab 10 MG/ML Intravenous Solution	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)
Nivolumab/Relatlimab (80 mg)	Relatlimab 10 MG/ML Intravenous Solution	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)
Nivolumab/Relatlimab (240 mg)	Nivolumab 10 MG/ML Intravenous Solution	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)
Nivolumab/Relatlimab (240 mg)	Relatlimab 10 MG/ML Intravenous Solution	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)

Primary Outcome Measures

Name	Time	Method
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

Name	Time	Method
Disease-free survival rate at 12 months	12 months	Assessment of disease-free survival rate at 12 months per Response Evaluation Criteria In Solid Tumors (RECIST) version 1.1
Overall survival rate at 12 months	12 months
Morbidity	within 90 days after surgery	Estimation of morbidity within 90 days after surgery
Mortality	within 90 days after surgery	Estimation of mortality within 90 days after surgery
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	After 3, 6, 9 and 12 months post-surgery	Objective radiological response rate per Response Evaluation Criteria In Solid Tumors (RECIST) version 1.1

Trial Locations

Locations (4)

Thoraxklinik Heidelberg gGmbH-Universitätsklinikum Heidelberg; 🇩🇪 Heidelberg, Germany

University Hospital Essen; 🇩🇪 Essen, Germany

Netherlands Cancer Institute; 🇳🇱 Amsterdam, Netherlands

Jessa Hospital Hasselt; 🇧🇪 Hasselt, Belgium