NSCLC Stage IIPhase 2NEOpredictNCT04205552
Neoadjuvant Nivolumab Combination Treatment in Resectable Non-small Cell Lung Cancer Patients
A Phase 2 study testing Nivolumab 10 MG/ML Intravenous Solution and Relatlimab 10 MG/ML Intravenous Solution in people with NSCLC Stage II and NSCLC, Stage IIIA, run by University Hospital, Essen at 4 sites in 3 countries.
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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- NSCLC Stage II, NSCLC, Stage IIIA, NSCLC, Stage I
- What is being tested?
- Nivolumab 10 MG/ML Intravenous Solution and Relatlimab 10 MG/ML Intravenous Solution
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 90 participants
- Where
- 4 sitesin 3 countries
- Study dates
- 4 Mar 2020to 27 Nov 2025
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Show all 16Show fewer
- 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
Trial locations and contacts
4 sites in 3 countries.
4 sites in 3 countries
Germany2 sites
University Hospital Essen
Essen
Thoraxklinik Heidelberg gGmbH-Universitätsklinikum Heidelberg
Heidelberg, 69126
About this study
Official title: 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.
- Conditions
- NSCLC Stage II, NSCLC, Stage IIIA, NSCLC, Stage I
- Being tested
- Nivolumab 10 MG/ML Intravenous Solution, Relatlimab 10 MG/ML Intravenous Solution
- Medical subject headings
- Carcinoma, Non-Small-Cell Lung
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Nivolumab 10 MG/ML Intravenous SolutionDrug
Neoadjuvant 2 cycles, every two weeks (q2w) Nivolumab 240 mg i.v. over 30 min
Relatlimab 10 MG/ML Intravenous SolutionDrug
Neoadjuvant 2 cycles, every two weeks (q2w) Relatlimab 80 mg i.v. over 30 min
| Study group | Role | What they receive |
|---|---|---|
| Nivolumab | Experimental | Nivolumab 2 cycles, every two weeks (q2w)
o Nivolumab 240 mg i.v. over 30 min Receives: 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) Receives: 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) Receives: Drug: Nivolumab 10 MG/ML Intravenous Solution; Drug: Relatlimab 10 MG/ML Intravenous Solution |
What is being measured
The primary outcome is the main question the study is designed to answer.
Feasibility of four weeks of preoperative immunotherapy with Nivolumab, Nivolumab plus Relatlimab (80 mg), and Nivolumab plus Relatlimab (240 mg)
Measured: Within 43 days after first study medication
Secondary outcomes (7)
Estimation of pathological tumor response rate
Measured: Within 43 days after first study medication (day of surgery)
Estimation of curative (R0) resection rate
Measured: 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
Measured: 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
Measured: 12 months
Overall survival rate at 12 months
Measured: 12 months
Morbidity
Estimation of morbidity within 90 days after surgery
Measured: within 90 days after surgery
Mortality
Estimation of mortality within 90 days after surgery
Measured: within 90 days after surgery
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Dec 2019
- Study start4 Mar 2020
- Primary completion27 Nov 2025
- Study completion27 Nov 2025
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for NSCLC Stage IIStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 90 participants (actual)
Sponsor and investigators
- Lead sponsor
- University Hospital, Essen
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Martin Schuler, Prof. Dr., Principal investigator, University Hospital, Essen
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04205552
- Sponsor's protocol ID
- CA224-063
- Acronym
- NEOpredict
- Status last verified
- Jun 2026
- First submitted
- 16 Dec 2019
- Last updated
- 11 Jun 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
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.
PubMed 38689060
Study at a glance
From the registry record, last updated by the sponsor on 11 Jun 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Neoadjuvant Nivolumab Combination Treatment in Resectable Non-small Cell Lung Cancer Patients: Defining Optimal Combinations and Determinants of Immunological Response
- ClinicalTrials.gov ID
- NCT04205552
- Acronym / sponsor ID
- NEOpredict / CA224-063
- Conditions
- NSCLC Stage II, NSCLC, Stage IIIA, NSCLC, Stage I
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 90 participants (actual)
- Lead sponsor
- University Hospital, EssenUniversity, hospital or other
- Study start
- 4 Mar 2020 (actual)
- Primary completion
- 27 Nov 2025 (actual)
- Study completion
- 27 Nov 2025 (actual)
- First posted
- 19 Dec 2019 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Nivolumab | Experimental | Drug: Nivolumab 10 MG/ML Intravenous SolutionNivolumab 2 cycles, every two weeks (q2w) o Nivolumab 240 mg i.v. over 30 min |
| Nivolumab/Relatlimab (80 mg) | Experimental | Drug: Nivolumab 10 MG/ML Intravenous Solution, Drug: Relatlimab 10 MG/ML Intravenous SolutionNivolumab/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) | Experimental | Drug: Nivolumab 10 MG/ML Intravenous Solution, Drug: Relatlimab 10 MG/ML Intravenous SolutionNivolumab/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) |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- 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)
Key exclusion criteria (16 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Nivolumab 10 MG/ML Intravenous SolutionNeoadjuvant 2 cycles, every two weeks (q2w) Nivolumab 240 mg i.v. over 30 min | Drug | Nivolumab, Nivolumab/Relatlimab (240 mg), Nivolumab/Relatlimab (80 mg) |
| Relatlimab 10 MG/ML Intravenous SolutionNeoadjuvant 2 cycles, every two weeks (q2w) Relatlimab 80 mg i.v. over 30 min | Drug | Nivolumab/Relatlimab (240 mg), Nivolumab/Relatlimab (80 mg) |
Primary outcome
Feasibility of four weeks of preoperative immunotherapy with Nivolumab, Nivolumab plus Relatlimab (80 mg), and Nivolumab plus Relatlimab (240 mg)
Time frame: Within 43 days after first study medication
7 secondary outcomes
Estimation of pathological tumor response rate
Time frame: Within 43 days after first study medication (day of surgery)
Estimation of curative (R0) resection rate
Time frame: Within 43 days after first study medication (day of surgery)
Objective radiological response rate
Time frame: After 3, 6, 9 and 12 months post-surgery
Disease-free survival rate at 12 months
Time frame: 12 months
Overall survival rate at 12 months
Time frame: 12 months
Morbidity
Time frame: within 90 days after surgery
Mortality
Time frame: within 90 days after surgery
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 11 Jun 2026.
- Results publication: PubMed 38689060Schuler 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.
- Neoadjuvant nivolumab with or without relatlimab in resectable non-small-cell lung cancer: a randomized phase 2 trialLink provided by the sponsor.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Martin Schuler, Prof. Dr. principal investigator
University Hospital, Essen
4 sites in 3 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Nivolumab 10 MG/ML Intravenous Solution and Relatlimab 10 MG/ML Intravenous Solution in people with NSCLC Stage II and NSCLC, Stage IIIA, run by University Hospital, Essen at 4 sites in 3 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 16 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 11 Jun 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 4 sites in Germany, Belgium, Netherlands. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Feasibility of four weeks of preoperative immunotherapy with Nivolumab, Nivolumab plus Relatlimab (80 mg), and Nivolumab plus Relatlimab (240 mg) (time frame: Within 43 days after first study medication). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04205552, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 11 Jun 2026.