Clinical trial NCT04205552: Neoadjuvant Nivolumab Combination Treatment in Resectable Non-small Cell Lung Cancer Patients
Official title: Neoadjuvant Nivolumab Combination Treatment in Resectable Non-small Cell Lung Cancer Patients: Defining Optimal Combinations and Determinants of Immunological Response
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: NSCLC Stage II
NSCLC, Stage IIIA
NSCLC, Stage I
Lead sponsor: University Hospital, Essen
Sponsor class: OTHER
First posted: 2019-12-19
Enrollment: 90
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: 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

Primary outcomes:
measure: Feasibility of four weeks of preoperative immunotherapy with Nivolumab, Nivolumab plus Relatlimab (80 mg), and Nivolumab plus Relatlimab (240 mg)
timeFrame: Within 43 days after first study medication
Secondary outcomes:
measure: Estimation of pathological tumor response rate
timeFrame: Within 43 days after first study medication (day of surgery)
measure: Estimation of curative (R0) resection rate
timeFrame: Within 43 days after first study medication (day of surgery)
measure: Objective radiological response rate
timeFrame: After 3, 6, 9 and 12 months post-surgery
measure: Disease-free survival rate at 12 months
timeFrame: 12 months
measure: Overall survival rate at 12 months
timeFrame: 12 months
measure: Morbidity
timeFrame: within 90 days after surgery
measure: Mortality
timeFrame: within 90 days after surgery
Other outcomes:
Locations:
city: Hasselt
country: Belgium
facility: Jessa Hospital Hasselt
city: Essen
country: Germany
facility: University Hospital Essen
city: Heidelberg
country: Germany
facility: Thoraxklinik Heidelberg gGmbH-Universitätsklinikum Heidelberg
city: Amsterdam
country: Netherlands
facility: Netherlands Cancer Institute
Study officials:
affiliation: University Hospital, Essen
name: Martin Schuler, Prof. Dr.
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.