Adaptive Chemotherapy for Pd-l1 High REsEctablE NSCLC: A Chemo-PHREE Trial

Starting soon · Phase 2

Conditions studied: Nsclc, NSCLC Stage II, NSCLC, Stage III, NSCLC Stage IIIB, Resectable Lung Non-Small Cell Carcinoma

In brief

This research study is being done to find out if a drug called cemiplimab is safe in adult patients who have non-small cell lung cancer (NSCLC) that can be surgically removed (resectable Stage II, IIIA, or select IIIB NSCLC). The purpose of this study is also to look at how well the study drug works and whether certain patients can skip chemotherapy before their surgery. The goal is to see if they can safely avoid the harsh side effects of chemo and still have a successful outcome. The investigators are doing this study because the investigators want to find out if this treatment approach is better or worse than the usual approach for early-stage NSCLC that can be surgically removed. The usual approach for the participants type of cancer is treatment with a combination of platinum-doublet chemotherapy and an immune checkpoint inhibitor (ICI) such as cemiplimab (LIBTAYO®) given before the tumor is surgically removed. (Immune checkpoint is a normal part of the immune system used to prevent an immune response from becoming so strong that it inadvertently destroys healthy cells in the body). Cemiplimab is given via infusion and will be administered at the study center. Everyone on the study will get the active study drug, cemiplimab. No one will get placebo. Placebos look like the study drug but don't have medicine in them. Infusion of cemiplimab will be given for 2 cycles followed by an evaluation. An evaluation means that participants will have imaging studies ("scans") done to see if the tumor has changed. After the scans, participants may receive one final cycle of cemiplimab followed by resection (surgery to remove the tumor) or combination chemotherapy plus cemiplimab for 2 cycles followed by resection.

Key facts

Study ID: NCT07746388
Run by: University of Maryland, Baltimore
People needed: 30
Starts: 2026-09-01
Expected to finish: 2031-09-01
Last updated by the study team: 2026-08-07

Who can join

Age: 18 and older. Sex: any. Healthy volunteers: not accepted.

You may qualify if…

Age 18 years or older at time of study entry
Eastern cooperative oncology group (ECOG) performance status of 0 or 1
Participants with histologically confirmed stage II-IIIB(N2) NSCLC (per the 9th International Association for the Study of Lung Cancer) with disease that is considered resectable prior to initiation of systemic therapy.
Subject cases must be reviewed in a multidisciplinary thoracic tumor board setting prior to enrollment to allow for adequate discussion regarding the appropriateness for resection.
Participants must have a tumor tissue sample available for biomarker testing, including PD-L1 IHC testing and sequencing to confirm EGFR/ALK status. Assessment of PD-L1 IHC, EGFR/ALK status may be performed locally through a CLIA approved laboratory testing method.
a. Tissue source may be a formalin fixed paraffin block (FFPE) of a previous tumor biopsy sample. Source of biomarker testing may be obtained from archived tissue if adequate or from a new biopsy, if needed and clinically indicated.
Participants must have established PD-L1 Tumor Proportion Score (TPS) expression > or equal to 50%, assessed locally through a CLIA approved laboratory testing method.
All suspicious mediastinal/hilar lymph nodes including those that are pathologically enlarged or FDG avid on PET/CT require further sampling for pathological confirmation if accessible by mediastinoscopy, thoracoscopy, or EBUS.
Absence of major associated pathologies that increase the surgery risk to an unacceptable level
Pulmonary function capacity (eg. FVC, FEV1, TLC, and DLCO) capable of tolerating proposed lung resection according to surgeon.
Adequate normal organ and marrow function defined below:
Platelet count > or equal to 100,000/mm3
Hemoglobin > or equal to 8 g/dL
Absolute neutrophil count (ANC) > or equal to 1000/mm3
Creatinine ≤ 1.5 x ULN or creatinine clearance (CrCl) > or equal to 40 mL/min
Total bilirubin ≤ 1.5 x ULN (except subjects with Gilbert Syndrome who can have total bilirubin < 3.0 mg/dL)
AST, ALT, Alkaline phosphatase ≤ 3 x ULN per local testing 11. Subjects are deemed capable of giving informed consent and must have signed and dated an IRB approved written informed consent form. This written consent must be obtained before the performance of any protocol related procedures that are not part of normal standard of care. 12. Women of childbearing potential (WOCBP) must have negative serum or urine pregnancy testing within 30 days of study start

You may not qualify if…

Presence of locally advanced unresectable (regardless of stage) or metastatic disease (stage IV).
Participants with large-cell neuroendocrine carcinoma tumor or small cell carcinoma histology, including those with presence of mixed histology.
Participants with known sensitizing EGFR mutations (L858R, Exon 19 deletion, Exon 20 insertion, atypical mutations including G719X L861Q, S768I) or ALK translocation via local CLIA approved testing methods.
a. For patients in whom more comprehensive testing is performed, those with identified targetable alterations in ROS1, NTRK, RET, METex14, HER2 genes will also be excluded. Screening for these specific alterations (ROS1/NTRK/RET/METex14/HER2), however, are not required for enrollment.
Participants with brain metastases are excluded from this study. All patients should have pre-study MRI brain or CT head with contrast to confirm the absence of intracranial disease, per standard of care staging procedures.
Prior therapy with an anti-PD-(L)1, anti-CTLA-4 antibody or any other antibody targeting t-cell co-regulatory pathways.
Active prior malignancy within the previous 3 years, except for locally curable cancers that have been apparently cured, such as basal or squamous cell skin cancer, superficial bladder cancer or carcinoma in situ of the prostate, cervix or breast.
History of allogeneic organ transplantation.
Presence of a condition or abnormality that in the opinion of the Investigator would compromise the safety of the patient or the quality of the data.
New York Heart Association heart failure classifications of Class II, III, or IV; or myocardial infarction, or acute coronary syndrome within 12 months of first dose of study medication; or Transient ischemic attack or stroke within 1 year
Any condition that requires ongoing/continuous corticosteroid therapy (>10 mg prednisone/day or anti-inflammatory equivalent) within 1 week prior to the first dose of study medication. Participants who require a brief course of steroids (up to 2 days in the week before enrollment) or physiologic replacement are not excluded.
Ongoing or significant autoimmune disease that required treatment with systemic immunosuppressive treatments within the last 5 years. Note: The following are not exclusionary: vitiligo, childhood asthma that has resolved, endocrinopathies (such as hypothyroidism or type 1 diabetes) that require only hormone replacement, or psoriasis that does not require systemic treatment.
Any infection requiring hospitalization or treatment with IV anti-infectives within 2 weeks of first dose of study medication
Uncontrolled infection with HIV, hepatitis B or hepatitis C infection, diagnosis of immunodeficiency, and/or tuberculosis (active or latent).
Participants with known controlled HIV infection (undetectable viral load on HIV RNA PCR) and CD4 count above 350 either spontaneously or on a stable antiviral regimen are eligible. For these participants monitoring will be performed per local standards.
Participants with HBsAg positive who have controlled infection (serum HBV DNA PCR that is below the limit of detection and receiving anti-viral therapy for hepatitis B) are eligible. Participants with controlled infections must undergo periodic monitoring of HBV DNA. Participants must remain on anti-viral therapy for at least 6 months beyond the last dose of investigational study medication.
Participants with HBsAg negative but total HBcAb positive are permitted with the following requirements: If serum HBV DNA PCR is above the limit of detection at screening, initiate HBV antiviral therapy before study entry. If serum HBV DNA PCR is below the limit of detection, periodic monitoring of HBsAg must be performed.
Participants who are HCV Ab+ who have controlled infection (undetectable HCV RNA by PCR either spontaneously or in eligible
Receipt of a live vaccine within 4 weeks of start of study medication
Receipt of COVID-19 vaccination within 1 week of planned start of study medication or for which the planned COVID-19 vaccinations would not be completed 1 week prior to start of study medication.
Known hypersensitivity to the active substances or to any of the excipients.
WOCBP* and men** who are unwilling to practice highly effective contraception prior to the initial dose/start of the first treatment, during the study, and for at least 4 months after the last dose of cemiplimab. Highly effective contraceptive measures include:
Stable use of combined (estrogen and progestogen containing) hormonal contraception (oral, intravaginal, transdermal) or progestogen-only hormonal contraception (oral, injectable, implantable) associated with inhibition of ovulation initiated 2 or more menstrual cycles prior to screening;
Intrauterine device; intrauterine hormone-releasing system;
Bilateral tubal occlusion/ligation;

Full record on ClinicalTrials.gov

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