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

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

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.

Study Overview

• Status: Recruiting
• Conditions: NSCLC, Stage I; NSCLC Stage II; NSCLC, Stage IIIA
• Intervention / Treatment: Drug: Nivolumab 10 MG/ML Intravenous Solution; Drug: Relatlimab 10 MG/ML Intravenous Solution

• Study Type: Interventional
• Enrollment (Estimated): 90
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Chiara Nicolini, PhD; Phone Number: 0049 201 723 44708; Email: chiara.nicolini@uk-essen.de

Study Locations

• Belgium
  • Hasselt, Belgium
    • Recruiting
    • Jessa Hospital Hasselt
• Germany
  • Essen, Germany
    • Recruiting
    • University Hospital Essen
  • Heidelberg, Germany, 69126
    • Recruiting
    • Thoraxklinik Heidelberg gGmbH-Universitätsklinikum Heidelberg
• Netherlands
  • Amsterdam, Netherlands
    • Recruiting
    • Netherlands Cancer Institute

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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 Plan

How is the study designed?

Design Details

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

Number of Arms

3

Arms and Interventions

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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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

Collaborators and Investigators

• Sponsor: University Hospital, Essen
• Investigators: Principal Investigator: Martin Schuler, Prof. Dr., University Hospital, Essen

Study record dates

Study Major Dates

• Study Start (Actual): March 4, 2020
• Primary Completion (Estimated): March 1, 2025
• Study Completion (Estimated): June 1, 2025

Study Registration Dates

• First Submitted: December 16, 2019
• First Submitted That Met QC Criteria: December 17, 2019
• First Posted (Actual): December 19, 2019

Study Record Updates

• Last Update Posted (Actual): August 14, 2023
• Last Update Submitted That Met QC Criteria: August 10, 2023
• Last Verified: August 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Neoplasms; Lung Diseases; Neoplasms by Site; Respiratory Tract Neoplasms; Thoracic Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Carcinoma, Non-Small-Cell Lung; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Antineoplastic Agents, Immunological; Immune Checkpoint Inhibitors; Nivolumab; Pharmaceutical Solutions; Relatlimab
• Other Study ID Numbers: CA224-063

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No