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

NCT07746388 | Not Yet Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: 25114GCCC ; HP-00117517
• Study Type: interventional
• Target: 30
• Locations: 0 countries
• Sites: N/A

Brief Summary

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.

Conditions

NSCLC Stage II; NSCLC, Stage III; NSCLC Stage IIIB; Nsclc; Resectable Lung Non-Small Cell Carcinoma

Outcome Measures

Primary Outcomes (1)

• Major pathologic response (MPR)

  MPR is defined as ≤ 10% viable tumor cells in resected tumor after complete evaluation in the resected lung cancer specimen as determined by central pathology review and described by IASLC 2020 assessment criteria. The measure of interest is the proportion of treated patients with ≤ 10% residual viable tumor cells within all resected tissue as confirmed by the central pathology review.

  At time of surgery

Secondary Outcomes (5)

• Feasibility of neoadjuvant cemiplimab

  ≤ 42 days from last dose of systemic therapy

• Assessment of AEs and SAEs [Safety]

  Occurring up until 100 days after the last dose of study treatment or 30 days following surgery, whichever is longer.

• Pathologic Complete Response (pCR)

  At time of surgery

• Event free survival (EFS)

  Up to 24 months from time of treatment initiation

• Overall survival (OS)

  Up to 24 months from time of treatment initiation

Study Arms (1)

Treatment with Cemiplimab

EXPERIMENTAL

Cemiplimab 350 mg IV administered every 3 weeks Will be given for at least 3 pre-operative doses, with potential 4th dose pending interim radiographic assessment after cycle 2 of treatment.

Drug: Cemiplimab

Interventions

Cemiplimab DRUG

Cemiplimab 350 mg IV administered every 3 weeks

Treatment with Cemiplimab

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

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

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.
• 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.

Sponsors & Collaborators

• University of Maryland, Baltimore: lead
• Regeneron Pharmaceuticals: collaborator

Related Publications (5)

• Bray F, Laversanne M, Sung H, Ferlay J, Siegel RL, Soerjomataram I, Jemal A. Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2024 May-Jun;74(3):229-263. doi: 10.3322/caac.21834. Epub 2024 Apr 4.

  PMID: 38572751 BACKGROUND

• Rami-Porta R, Nishimura KK, Giroux DJ, Detterbeck F, Cardillo G, Edwards JG, Fong KM, Giuliani M, Huang J, Kernstine KH Sr, Marom EM, Nicholson AG, Van Schil PE, Travis WD, Tsao MS, Watanabe SI, Rusch VW, Asamura H; Members of the IASLC Staging and Prognostic Factors Committee and of the Advisory Boards, and Participating Institutions. The International Association for the Study of Lung Cancer Lung Cancer Staging Project: Proposals for Revision of the TNM Stage Groups in the Forthcoming (Ninth) Edition of the TNM Classification for Lung Cancer. J Thorac Oncol. 2024 Jul;19(7):1007-1027. doi: 10.1016/j.jtho.2024.02.011. Epub 2024 Mar 4.

  PMID: 38447919 BACKGROUND

• Forde PM, Chaft JE, Smith KN, Anagnostou V, Cottrell TR, Hellmann MD, Zahurak M, Yang SC, Jones DR, Broderick S, Battafarano RJ, Velez MJ, Rekhtman N, Olah Z, Naidoo J, Marrone KA, Verde F, Guo H, Zhang J, Caushi JX, Chan HY, Sidhom JW, Scharpf RB, White J, Gabrielson E, Wang H, Rosner GL, Rusch V, Wolchok JD, Merghoub T, Taube JM, Velculescu VE, Topalian SL, Brahmer JR, Pardoll DM. Neoadjuvant PD-1 Blockade in Resectable Lung Cancer. N Engl J Med. 2018 May 24;378(21):1976-1986. doi: 10.1056/NEJMoa1716078. Epub 2018 Apr 16.

  PMID: 29658848 BACKGROUND

• Rosner S, Reuss JE, Zahurak M, Zhang J, Zeng Z, Taube J, Anagnostou V, Smith KN, Riemer J, Illei PB, Broderick SR, Jones DR, Topalian SL, Pardoll DM, Brahmer JR, Chaft JE, Forde PM. Five-Year Clinical Outcomes after Neoadjuvant Nivolumab in Resectable Non-Small Cell Lung Cancer. Clin Cancer Res. 2023 Feb 16;29(4):705-710. doi: 10.1158/1078-0432.CCR-22-2994.

  PMID: 36794455 BACKGROUND

• Forde PM, Spicer J, Lu S, Provencio M, Mitsudomi T, Awad MM, Felip E, Broderick SR, Brahmer JR, Swanson SJ, Kerr K, Wang C, Ciuleanu TE, Saylors GB, Tanaka F, Ito H, Chen KN, Liberman M, Vokes EE, Taube JM, Dorange C, Cai J, Fiore J, Jarkowski A, Balli D, Sausen M, Pandya D, Calvet CY, Girard N; CheckMate 816 Investigators. Neoadjuvant Nivolumab plus Chemotherapy in Resectable Lung Cancer. N Engl J Med. 2022 May 26;386(21):1973-1985. doi: 10.1056/NEJMoa2202170. Epub 2022 Apr 11.

  PMID: 35403841 BACKGROUND

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Interventions

cemiplimab

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Central Study Contacts

Samuel Rosner, MD

CONTACT

410-328-2575; samuel.rosner@umm.edu

Kaylee Martin

CONTACT

(410) 328-2288; kaylee.martin@umm.edu

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Single Arm Phase II trial

Study Record Dates

• First Submitted: July 29, 2026
• First Posted: August 5, 2026
• Study Start: September 1, 2026
• Primary Completion (Estimated): September 1, 2030
• Study Completion (Estimated): September 1, 2031
• Last Updated: August 7, 2026

Record last verified: 2026-08