Non-small Cell Lung Cancer Stage IIIPhase 2NEO-SURGNCT06449313
Neoadjuvant Chemo-Immunotherapy and Surgical Resection in Locally Advanced Non-small Cell Lung Cancer With N3 Lymph Node or Other High Risk Features
A Phase 2 study testing Cemiplimab-Rwlc in people with Non-small Cell Lung Cancer Stage III, run by Georgetown University at 3 sites in United States.
Trial summary
The goal of this clinical trial is to learn about neoadjuvant cemiplimab with histology-specific chemotherapy followed by resection and adjuvant cemiplimab in stage 3 non-small cell lung cancer (NSCLC) with select N3 lymph node involvement or other high-risk subsets in which there is no consensus on resectability. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Non-small Cell Lung Cancer Stage III
- What is being tested?
- Cemiplimab-Rwlc
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 21 participants
- Where
- 3 sitesUnited States
- Study dates
- Nov 2026to Sep 2032
- Phase
- Phase 2
- Are there results?
- Not yet: the study is under way
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
- Age ≥ 18 years at time of signing the informed consent form (ICF).
- Histologically or cytologically confirmed stage 3 Non-Small Cell Lung Cancer (NSCLC) as assessed per the 8th American Joint Committee on Cancer (AJCC) that meets one of the below criteria:
- Pathologically-confirmed contralateral mediastinal or ipsilateral supraclavicular (N3) lymph node involvement. Primary tumor and involved lymph nodes should otherwise be deemed appropriate for resection/removal with curative intent as assessed by the treating surgeon prior to study enrollment.
- Pathologically-confirmed T4N2 NSCLC.
- Pathologically-confirmed T4inv with any N.
- Pathologically-confirmed T3invN2.
Show all 28Show fewer
- Pathologically-confirmed Pancoast T3 or T4 with N2 involvement.
- Any T-stage with bulky N2 lymph node involvement defined by lymph node short axis ≥ 2.5cm.
- Absence of major associated pathologies and co-morbidities that elevate surgery risk to a prohibitive level, as assessed by treating surgeon prior to study enrollment.
- Pulmonary function capacity capable of tolerating the lung resection proposed by the treating surgeon.
- EGFR, ALK, wild-type assessed via any CLIA-certified tissue testing platform. Documentation of EGFR and ALK status is not required for pure squamous NSCLC histology.
- Eastern Cooperative Oncology Group (ECOG) Performance Status of 0-1.
- Adequate hematologic and end-organ function, defined by the following laboratory test results, obtained within 21 days prior to initiation of study treatment:
- Absolute Neutrophil count (ANC) ≥ 1.0 x 10^9/L (1000/uL) without granulocyte colony-stimulating factor support
- Platelet count ≥ 100 x 10^9/L (100,000/uL) without transfusion
- Hemoglobin ≥ 90 g/L (9.0 g/dL) (Patients may be transfused to meet this criterion.)
- Aspartate aminotransferase (AST) and Alanine aminotransferase (ALT) </= 3 x upper limit of normal (ULN)
- Serum bilirubin </= 2.0 x ULN with the following exception: Patients with known Gilbert disease: serum bilirubin </= 3 x ULN
- Creatinine clearance ≥ 45 mL/min (calculated using the Cockcroft-Gault formula). If creatinine clearance determined by Cockcroft-Gault is <45 mL/min, another appropriate validated formula or 24hr urine collection may be used in consultation with the study PI.
- For patients not receiving therapeutic anticoagulation: INR (international normalised ratio) and aPTT (activated partial thromboplastin time) </= 1.5 x ULN. For patients receiving therapeutic anticoagulation: stable anticoagulant regimen defined as clinical stability on unchanged dose of therapeutic anticoagulation for ≥14 days.
- For women of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive methods, and agreement to refrain from donating eggs, as defined below:
- Women must remain abstinent or use highly effective contraceptive methods with a failure rate of < 1% per year during the treatment period and for at least 4 months after the final dose of study treatment. Women must refrain from donating eggs during this same period.
- A woman is considered to be of childbearing potential if she is postmenarchal, has not reached a postmenopausal state (≥ 12 continuous months of amenorrhea with no identified cause other than menopause), and has not undergone surgical sterilization (removal of ovaries and/or uterus). The definition of childbearing potential may be adapted for alignment with local guidelines or requirements.
- Examples of contraceptive methods with a failure rate of < 1% per year include bilateral tubal ligation, male sterilization, hormonal contraceptives that inhibit ovulation, hormone-releasing intrauterine devices, and copper intrauterine devices.
- The reliability of sexual abstinence should be evaluated in relation to the duration of the clinical trial and the preferred and usual lifestyle of the patient. Periodic abstinence (e.g., calendar, ovulation, symptothermal, or postovulation methods) and withdrawal are not adequate methods of contraception.
- For men: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive measures, and agreement to refrain from donating sperm, as defined below:
- With a female partner of childbearing potential who is not pregnant, or a female partner who is pregnant, men who are not surgically sterile must remain abstinent or use a condom plus an additional contraceptive method that together result in a failure rate of < 1% per year during the treatment period and for 4 months after the final dose of study treatment. Men must refrain from donating sperm during this this same period.
- The reliability of sexual abstinence should be evaluated in relation to the duration of the clinical trial and the preferred and usual lifestyle of the patient. Periodic abstinence (e.g., calendar, ovulation, symptothermal, or postovulation methods) and withdrawal are not adequate methods of contraception.
Who cannot join
- NSCLC with histology containing any of the following: large cell neuroendocrine carcinoma, small cell lung cancer.
- Tumor with direct invasion of: mediastinum, diaphragm, heart, great vessels, trachea, esophagus, vertebral body, or carina.
- Any other tumor characteristic making it not suitable for resection as determined by treating surgeon.
- Tumor with direct invasion of: myocardium, trachea, esophagus, vertebral body, or carina.
- Any M1 disease.
- >2 involved N3 lymph node stations.
Show all 35Show fewer
- Biopsy-confirmed involvement of contralateral hilar and/or contralateral supraclavicular lymph nodes
- Any other tumor- or patient-related characteristic that is prohibitive of attempted surgical resection upon multi-disciplinary team review.
- Any prior systemic therapy for index lung cancer, including immunotherapy, chemotherapy.
- History of malignancy requiring systemic therapy within 2 years prior to screening, with the exception of malignancies with a negligible risk of metastasis or death as assessed and confirmed by the study PI.
- Patients with a history of stage I NSCLC treated with resection or radiotherapy are eligible for inclusion.
- Active or history of clinically significant autoimmune disease that, in the opinion of the investigator, could compromise the health and safety of the patient if treated with anti-PD1 immunotherapy. Notable exceptions include:
- Patients with a history of autoimmune-related hypothyroidism who are on thyroid-replacement hormone.
- Patients with controlled Type 1 diabetes mellitus who are on an insulin regimen.
- Active or history of adrenal insufficiency on stable steroid regimen.
- Patients with eczema, psoriasis, lichen simplex chronicus, or vitiligo with dermatologic manifestations only are eligible for the study provided all of following conditions are met:
- Disease is well controlled at baseline and requires only low-potency topical corticosteroids ii. No occurrence of acute exacerbations of the underlying condition requiring psoralen plus ultraviolet A radiation, methotrexate, retinoids, biologic agents, oral calcineurin inhibitors, or high-potency oral corticosteroids within the previous 12 months
- History of idiopathic pulmonary fibrosis, organizing pneumonia (e.g., bronchiolitis obliterans), drug-induced pneumonitis, or idiopathic pneumonitis, or evidence of active pneumonitis on screening chest computed tomography (CT) scan.
- Known active tuberculosis.
- Known history of poorly controlled HIV.
- Patients living with HIV are allowed to enroll if: (1) they are clinically stable on appropriate highly active anti-retroviral therapy (HAART) with undetectable HIV viral load and CD4 count >350 and (2) the HAART regimen poses no unacceptable interactions with the prescribed anti-cancer therapies.
- Known history of poorly controlled hepatitis B or hepatitis C
- Patients with known hepatitis B (HepBsAg+) who have controlled infection (serum hepatitis B virus DNA PCR that is below the limit of detection AND receiving anti-viral therapy for hepatitis B) are permitted. Patients with controlled infections must undergo periodic monitoring of HBV DNA per local standards and must remain on anti-viral therapy for at least 6 months beyond the last dose of investigational study drug.
- Patients who are known hepatitis C virus antibody positive (HCV Ab+) who have controlled infection (undetectable HCV RNA by PCR either spontaneously or in response to a successful prior course of anti-HCV therapy) are permitted.
- Severe infection within 3 weeks prior to initiation of study treatment, including, but not limited to, hospitalization for complications of infection (including COVID-19), bacteremia, or severe pneumonia that, in the opinion of the investigator, may impact patient safety.
- Prior allogeneic stem cell or solid organ transplantation.
- Any treatment with a live, attenuated vaccine within 4 weeks prior to initiation of study treatment, or anticipation of need for such a vaccine during study treatment or within 5 months after the final dose of study treatment.
- Significant vascular and cardiovascular disease (e.g., New York Heart Association Class II or greater heart failure, unstable arrhythmia, aortic aneurysm requiring surgical repair or recent peripheral arterial thrombosis - including but not limited to myocardial infarction, transient ischemic attack, stroke or unstable angina) within 6 months prior to study treatment initiation.
- Treatment with systemic immunosuppressive medication (including, but not limited to: corticosteroids, cyclophosphamide, azathioprine, methotrexate, thalidomide, and anti-TNF-alpha agents) within 2 weeks prior to initiation of study treatment, or anticipation of need for systemic immunosuppressive medication during study treatment, with the following exceptions:
- Patients who received acute, low-dose systemic immunosuppressant medication or a one-time pulse dose of systemic immunosuppressant medication (e.g., 48 hours of corticosteroids for a contrast allergy) are eligible for the study after PI confirmation has been obtained.
- Patients who received mineralocorticoids (e.g., fludrocortisone), corticosteroids for chronic obstructive pulmonary disease (COPD) or asthma, or low-dose corticosteroids for orthostatic hypotension or adrenal insufficiency are eligible for the study.
- Any prior use of an immune checkpoint blockade therapy including agents directed against CTLA-4, PD-1, and PD-L1.
- History of severe allergic reaction or hypersensitivity to study drug components.
- Pregnancy or breastfeeding, or intention of becoming pregnant during study treatment or within 6 months after the final dose of study treatment.
- Women of childbearing potential must have a negative serum pregnancy test result within 14 days prior to initiation of study treatment.
Trial locations and contacts
3 sites in 1 country. Contact the study team or a site near you to ask about taking part.
United States3 sites, 3 recruiting
- Recruiting
UVA Comprehensive Cancer Center
Charlottesville, Virginia, 22908
Yaro Shvorak, CCRC, 434-297-7384, ys7cb@uvahealth.org
Ryan Gentzler, MD, MS
- Recruiting
Washington University School of Medicine-Sitemen Cancer Center
St Louis, Missouri, 63110
Medical Oncology Clinical Call Center, 314-747-1171, MedicalOncologyClinicalCallCenter@dom.wustl.edu
Ece Cali Daylan, MD, PhD
- Recruiting
Lombardi Comprehensive Cancer Center, Georgetown University
Washington D.C., District of Columbia, 20007
Jenny Crawford, RN, 202-687-0893, crawfojg@georgetown.edu
Joshua Reuss, MD
About this study
Official title: A Phase 2 Single-arm Study of Neoadjuvant Chemo-Immunotherapy and Surgical Resection in Locally Advanced Non-small Cell Lung Cancer With N3 Lymph Node Involvement or Other High Risk Features
The goal of this clinical trial is to learn about neoadjuvant cemiplimab with histology-specific chemotherapy followed by resection and adjuvant cemiplimab in stage 3 non-small cell lung cancer (NSCLC) with select N3 lymph node involvement or other high-risk subsets in which there is no consensus on resectability.
The main question it aims to answer is whether patients with stage 3 NSCLC with involvement of lymph nodes can undergo surgery to remove the cancer after receiving treatment with chemotherapy + immunotherapy.
Participants will receive FDA-approved chemotherapy called platinum-doublet chemotherapy together with an immunotherapy drug targeting the immune marker PD-1 called cemiplimab. Patients will receive a 3 drug combination for 4 total treatments given every 3 weeks before surgery. After surgery, patients will have the option to undergo radiation therapy if it is recommended by their treatment team. After this, they will receive cemiplimab every 3 weeks for one year.
- Conditions
- Non-small Cell Lung Cancer Stage III
- Being tested
- Cemiplimab-Rwlc
- Keywords
- non-small cell lung cancer
- 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.
Cemiplimab-RwlcDrug
Also called Libtayo
350 mg every 3 weeks, intravenously, on day 1 of a 21 day cycle for 4 cycles, then every 3 weeks after surgery for 1 year.
| Study group | Role | What they receive |
|---|---|---|
| Cemiplimab plus chemotherapy | Experimental | cemiplimab given with standard of care chemotherapy for 4 treatments/cycles before surgery and then every 3 weeks for 1 year after surgery. Receives: Drug: Cemiplimab-Rwlc |
What is being measured
The primary outcome is the main question the study is designed to answer.
Pathologic complete response (pCR) rate
Pathologic complete response (pCR): 0% viable tumor in primary tumor and resected lymph nodes.
Measured: 12 weeks
Secondary outcomes (5)
Objective Response Rate (ORR)
Defined as imaging response according to RECIST v1.1 (Eisenhauer et al. 2009).
Measured: 1 year
Rate of R0 Resection
Rate of R0 Resection: Defined as percentage of patients undergo complete tumor resection with negative margins.
Measured: 12 weeks
Major pathologic response (MPR) rate
MPR Rate: Defined as the percentage of patients with resection specimen that shows ≤10% viable tumor in resected lung and lymph nodes
Measured: 12 weeks
Disease-free Survival (DFS)
DFS: Time from first dose of neoadjuvant treatment to documented disease recurrence. Where possible, date of pathologic confirmation of recurrence should be used over date of radiographic imaging showing findings concerning for recurrence.
Measured: 5 years
Overall Survival (OS)
Time first dose of neoadjuvant treatment to death.
Measured: 5 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Jun 2024
- Study startNov 2026 (estimated)
- Primary completionDec 2027 (estimated)
- Study completionSep 2032 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Non-small Cell Lung Cancer Stage IIIStudies of the same condition, open and under way.
- More trials run by Georgetown UniversityThe sponsor's other registered studies.
- 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
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 21 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Georgetown University
- Sponsor type
- University, hospital or other
- Collaborators
- Regeneron Pharmaceuticals
- Responsible party
- Sponsor
- Investigators
- Joshua Reuss, MD, Principal investigator, Georgetown University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06449313
- Sponsor's protocol ID
- STUDY00007668
- Acronym
- NEO-SURG
- Status last verified
- Oct 2026
- First submitted
- 3 Jun 2024
- Last updated
- 6 Oct 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 6 Oct 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 2 Single-arm Study of Neoadjuvant Chemo-Immunotherapy and Surgical Resection in Locally Advanced Non-small Cell Lung Cancer With N3 Lymph Node Involvement or Other High Risk Features
- ClinicalTrials.gov ID
- NCT06449313
- Acronym / sponsor ID
- NEO-SURG / STUDY00007668
- Conditions
- Non-small Cell Lung Cancer Stage III
- Keywords
- non-small cell lung cancer
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 21 participants (estimated)
- Lead sponsor
- Georgetown UniversityUniversity, hospital or other
- Collaborators
- Regeneron Pharmaceuticals
- Study start
- Nov 2026 (estimated)
- Primary completion
- Dec 2027 (estimated)
- Study completion
- Sep 2032 (estimated)
- First posted
- 10 Jun 2024 (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 goal of this clinical trial is to learn about neoadjuvant cemiplimab with histology-specific chemotherapy followed by resection and adjuvant cemiplimab in stage 3 non-small cell lung cancer (NSCLC) with select N3 lymph node involvement or other high-risk subsets in which there is no consensus on resectability.
The main question it aims to answer is whether patients with stage 3 NSCLC with involvement of lymph nodes can undergo surgery to remove the cancer after receiving treatment with chemotherapy + immunotherapy.
Participants will receive FDA-approved chemotherapy called platinum-doublet chemotherapy together with an immunotherapy drug targeting the immune marker PD-1 called cemiplimab. Patients will receive a 3 drug combination for 4 total treatments given every 3 weeks before surgery. After surgery, patients will have the option to undergo radiation therapy if it is recommended by their treatment team. After this, they will receive cemiplimab every 3 weeks for one year.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Cemiplimab plus chemotherapy | Experimental | Drug: Cemiplimab-Rwlccemiplimab given with standard of care chemotherapy for 4 treatments/cycles before surgery and then every 3 weeks for 1 year after surgery. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (28 listed)
- Age ≥ 18 years at time of signing the informed consent form (ICF).
- Histologically or cytologically confirmed stage 3 Non-Small Cell Lung Cancer (NSCLC) as assessed per the 8th American Joint Committee on Cancer (AJCC) that meets one of the below criteria:
- Absence of major associated pathologies and co-morbidities that elevate surgery risk to a prohibitive level, as assessed by treating surgeon prior to study enrollment.
- Pulmonary function capacity capable of tolerating the lung resection proposed by the treating surgeon.
- EGFR, ALK, wild-type assessed via any CLIA-certified tissue testing platform. Documentation of EGFR and ALK status is not required for pure squamous NSCLC histology.
Key exclusion criteria (35 listed)
- NSCLC with histology containing any of the following: large cell neuroendocrine carcinoma, small cell lung cancer.
- Tumor with direct invasion of: myocardium, trachea, esophagus, vertebral body, or carina.
- Any M1 disease.
- >2 involved N3 lymph node stations.
- Biopsy-confirmed involvement of contralateral hilar and/or contralateral supraclavicular lymph nodes
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 |
|---|---|---|
| Cemiplimab-RwlcAlso: Libtayo350 mg every 3 weeks, intravenously, on day 1 of a 21 day cycle for 4 cycles, then every 3 weeks after surgery for 1 year. | Drug | Cemiplimab plus chemotherapy |
Primary outcome
Pathologic complete response (pCR) rate
Time frame: 12 weeks
Pathologic complete response (pCR): 0% viable tumor in primary tumor and resected lymph nodes.
5 secondary outcomes
Objective Response Rate (ORR)
Time frame: 1 year
Rate of R0 Resection
Time frame: 12 weeks
Major pathologic response (MPR) rate
Time frame: 12 weeks
Disease-free Survival (DFS)
Time frame: 5 years
Overall Survival (OS)
Time frame: 5 years
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 6 Oct 2026.
- Individual participant dataSharing planned: No
Related trials for Non-small Cell Lung Cancer Stage III
RecruitingObservational study
A Prospective ,Multicenter ,Non-interventional ,Real-world Study Observing Changes in Molecular Markers Osimertinib Targeted Therapy in EGFRm NSCLC
Non Small Cell Lung Cancer
RecruitingPhase 3
A Study Evaluating Sotorasib Platinum Doublet Combination Versus Pembrolizumab Platinum Doublet Combination as a Front-Line Therapy in Participants With Stage IV or Advanced Stage IIIB/C Nonsquamous Non-Small Cell Lung Cancers (CodeBreaK 202)
Non-Small Cell Lung Cancer (NSCLC)
RecruitingPhase 3
Immunotherapy After Surgery for People Who Have No Remaining Cancer Cells After Standard Treatment for Early-Stage Non-Small Cell Lung Cancer, INSIGHT Trial
Lung Non-Small Cell Carcinoma, Stage II Lung Cancer AJCC v8
RecruitingPhase 3
A Study to Evaluate the Benefit of Adding Durvalumab After Chemotherapy, Durvalumab and Surgery in Patients With Early-stage, Operable, Non-small Cell Lung Cancer.
Non Small Cell Lung Cancer
Not yet recruiting
Moderately Hypofractionated Versus Conventional Chemoradiotherapy With Consolidation Immunotherapy in Patients With Unresectable, Non-Targetable Stage III Non Small Cell Lung Cancer (NSCLC)
Stage III NSCLC
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.
Joshua Reuss, MD principal investigator
Georgetown University
3 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Cemiplimab-Rwlc in people with Non-small Cell Lung Cancer Stage III, run by Georgetown University at 3 sites in United States.
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 28 inclusion and 35 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: looking for participants now, as of the sponsor's last update on 6 Oct 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites in United States. 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?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Joshua Reuss, MD (202-444-2223, Joshua.E.Reuss@gunet.georgetown.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Pathologic complete response (pCR) rate (time frame: 12 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 6 Oct 2026; AzTrials last refreshed its copy on 6 Nov 2026.