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

NCT04205552 | Recruiting Phase 2 DMC

• 1 other identifier: CA224-063
• Study Type: interventional
• Target: 90
• Locations: 3 countries
• Sites: 4

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.

Conditions

NSCLC Stage II; NSCLC, Stage IIIA; NSCLC, Stage I

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (7)

• 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

• Disease-free survival rate at 12 months

  12 months

• Overall survival rate at 12 months

  12 months

Study Arms (3)

Nivolumab

EXPERIMENTAL

Nivolumab 2 cycles, every two weeks (q2w) o Nivolumab 240 mg i.v. over 30 min

Drug: Nivolumab 10 MG/ML Intravenous Solution

Nivolumab/Relatlimab (80 mg)

EXPERIMENTAL

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; Drug: Relatlimab 10 MG/ML Intravenous Solution

Nivolumab/Relatlimab (240 mg)

EXPERIMENTAL

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; Drug: Relatlimab 10 MG/ML Intravenous Solution

Interventions

Nivolumab 10 MG/ML Intravenous Solution DRUG

Neoadjuvant 2 cycles, every two weeks (q2w) Nivolumab 240 mg i.v. over 30 min

Nivolumab; Nivolumab/Relatlimab (240 mg); Nivolumab/Relatlimab (80 mg)

Relatlimab 10 MG/ML Intravenous Solution DRUG

Neoadjuvant 2 cycles, every two weeks (q2w) Relatlimab 80 mg i.v. over 30 min

Nivolumab/Relatlimab (240 mg); Nivolumab/Relatlimab (80 mg)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• University Hospital, Essen: lead

Study Sites (4)

Jessa Hospital Hasselt

Hasselt, Belgium

RECRUITING

University Hospital Essen

Essen, Germany

RECRUITING

Thoraxklinik Heidelberg gGmbH-Universitätsklinikum Heidelberg

Heidelberg, 69126, Germany

RECRUITING

Netherlands Cancer Institute

Amsterdam, Netherlands

RECRUITING

Related Publications (1)

• Schuler M, Cuppens K, Plones T, Wiesweg M, Du Pont B, Hegedus B, Koster J, Mairinger F, Darwiche K, Paschen A, Maes B, Vanbockrijck M, Lahnemann D, Zhao F, Hautzel H, Theegarten D, Hartemink K, Reis H, Baas P, Schramm A, Aigner C. Neoadjuvant nivolumab with or without relatlimab in resectable non-small-cell lung cancer: a randomized phase 2 trial. Nat Med. 2024 Jun;30(6):1602-1611. doi: 10.1038/s41591-024-02965-0. Epub 2024 Apr 30.

  PMID: 38689060 RESULT

Related Links

• Neoadjuvant nivolumab with or without relatlimab in resectable non-small-cell lung cancer: a randomized phase 2 trial

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Interventions

Nivolumab; relatlimab

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Martin Schuler, Prof. Dr.

  University Hospital, Essen

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Chiara Nicolini, PhD

CONTACT

0049 201 723 44708; chiara.nicolini@uk-essen.de

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 16, 2019
• First Posted: December 19, 2019
• Study Start: March 4, 2020
• Primary Completion: March 1, 2025
• Study Completion: June 1, 2025
• Last Updated: May 9, 2024

Record last verified: 2024-05

Data Sharing

• IPD Sharing: Will not share

Locations

DE (2); NL (1); BE (1)