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

NSCLC, Stage I Clinical Trial

— NEOpredict  

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04205552
• Other study ID #: CA224-063
• Status: Recruiting
• Phase: Phase 2
• Start date: March 4, 2020
• Est. completion date: June 2025

Study information

• Verified date: May 2024
• Source: University Hospital, Essen
• Contact: Chiara Nicolini, PhD
• Phone: 0049 201 723 44708
• Email: chiara.nicolini[@]uk-essen.de
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 90
• Est. completion date: June 2025
• Est. primary completion date: March 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Carcinoma, Non-Small-Cell Lung
• NSCLC Stage II
• NSCLC, Stage I
• NSCLC, Stage IIIA

Intervention

Drug:
• Nivolumab 10 MG/ML Intravenous Solution
Neoadjuvant 2 cycles, every two weeks (q2w) Nivolumab 240 mg i.v. over 30 min
• Relatlimab 10 MG/ML Intravenous Solution
Neoadjuvant 2 cycles, every two weeks (q2w) Relatlimab 80 mg i.v. over 30 min

Locations

Country	Name	City	State
Belgium	Jessa Hospital Hasselt	Hasselt
Germany	University Hospital Essen	Essen
Germany	Thoraxklinik Heidelberg gGmbH-Universitätsklinikum Heidelberg	Heidelberg
Netherlands	Netherlands Cancer Institute	Amsterdam

Sponsors (1)

Lead Sponsor	Collaborator
University Hospital, Essen

Countries where clinical trial is conducted

Belgium,  Germany,  Netherlands, 

References & 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 wi — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Estimation of pathological tumor response rate		Within 43 days after first study medication (day of surgery)
Secondary	Estimation of curative (R0) resection rate		Within 43 days after first study medication (day of surgery)
Secondary	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
Secondary	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
Secondary	Overall survival rate at 12 months		12 months
Secondary	Morbidity	Estimation of morbidity within 90 days after surgery	within 90 days after surgery
Secondary	Mortality	Estimation of mortality within 90 days after surgery	within 90 days after surgery

External Links

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