Preoperative Radioimmunotherapy Versus Chemoimmunotherapy in NSCLC

NCT06623656 | Recruiting Phase 2 DMC FDA Drug FDA Device

• 1 other identifier: 24-02027124
• Study Type: interventional
• Target: 112
• Locations: 1 country
• Sites: 1

Brief Summary

The goal of this clinical trial is to learn if Cemiplimab with chemotherapy or Cemiplimab with stereotactic body radiation therapy (SBRT) works as treatment for stages IB, II, and III (N2) Non-Small Cell Lung Cancer (NSCLC). Before surgery to remove their lung cancer, participants will take:

1. 1.Cemiplimab with chemotherapy (Arm A) every 3 weeks for up to 3 doses, OR
2. 2.Cemiplimab every 3 weeks for up to 3 doses with SBRT (Arm B). SBRT will be given on day 1 before taking cemiplimab, then SBRT alone on day 2 and day 3.

Conditions

Carcinoma, Non-Small-Cell Lung

Keywords

Lung neoplasms; Bronchial Neoplasms; Carcinoma, bronchogenic; Neoplasms

Outcome Measures

Primary Outcomes (1)

• Number of participants with pathological complete response (pCR)

  pCR is defined as the absence of viable tumor in the tumor bed and the draining lymph nodes upon pathological review of the tissue.

  Surgical resection (Weeks 9-13).

Secondary Outcomes (14)

• Number of participants with Major Pathological Response (MPR)

  Surgical resection (Weeks 9-13).

• Number of participants with neoadjuvant treatment-related adverse events as assessed by CTCAE v5.0

  From cemiplimab with chemotherapy and cemiplimab with SBRT treatment start date (Day 1) to prior to surgical resection (Weeks 9-13).

• Surgical delay, mean/standard deviation

  From the date of the last dose of neoadjuvant cemiplimab treatment (Week 7) to surgical resection (Weeks 9-13).

• Number of participants with minimal access surgery

  Time of surgical resection (Week 9-13), after the last preoperative dose of cemiplimab.

• Change in number of participants with distant recurrence

  From cemiplimab with chemotherapy and cemiplimab with SBRT treatment start date (Day 1) to recurrence (Every 6 months for 3 years, then yearly for year 4-5).

Study Arms (2)

Cemiplimab with chemotherapy (Arm A)

EXPERIMENTAL

Before lung cancer surgery: 1. Cemiplimab 350 mg intravenously every 3 weeks up to 3 cycles. 2. Platinum-based chemotherapy intravenously every 3 weeks up to 3 cycles. After lung cancer surgery, cemiplimab 350 mg intravenously every 3 weeks for 4 treatments followed by 700 mg every 6 weeks for one year (11 treatments).

Drug: Cemiplimab; Drug: Platinum based chemotherapy

Cemiplimab with SBRT (Arm B)

EXPERIMENTAL

Before lung cancer surgery: 1. Cemiplimab 350 mg intravenously every 3 weeks up to 3 cycles. 2. SBRT on days 1, 2, and 3. After lung cancer surgery, cemiplimab 350 mg intravenously every 3 weeks for 4 treatments followed by 700 mg every 6 weeks for one year (11 treatments).

Drug: Cemiplimab; Radiation: Stereotactic body radiation therapy

Interventions

Cemiplimab DRUG

Intravenously

Also known as: Libtayo, REGN2810

Cemiplimab with SBRT (Arm B); Cemiplimab with chemotherapy (Arm A)

Platinum based chemotherapy DRUG

Intravenously

Also known as: Cisplatin, pemetrexed, gemcitabine, carboplatin, paclitaxel, docetaxel

Cemiplimab with chemotherapy (Arm A)

Stereotactic body radiation therapy RADIATION

8 Gy times 3 treatment days (Days 1-3)

Cemiplimab with SBRT (Arm B)

Eligibility Criteria

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

You may qualify if:

• Patients with histologically or cytologically proven clinical stages IB (T2aN0), II, and III(N2) NSCLC (according to AJCC version 9) eligible for surgical resection with curative intent. Patients with 2 synchronous NSCLC are allowed.
• Measurable disease, as defined by RECIST v1.1.
• Known PD-L1 expression.
• No known EGFR mutations or ALK fusions.
• Written informed consent and HIPAA obtained from the subject prior to performing any protocol-related procedures.
• Age \> 18 years at time of study entry.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
• No prior therapy for lung cancer
• Adequate organ and bone marrow function as defined below:
• Absolute neutrophil count (ANC) ≥1.5 x10(3)/uL
• Platelets ≥75 x10(3)/uL
• Hemoglobin ≥9 g/dL
• Serum creatinine ≤1.5 X upper limit of normal (ULN) OR calculated CrCl ≥50 ml/min (using the Cockcroft-Gault formula).
• Serum total bilirubin ≤1.5 X ULN, except in patients with clinically documented Gilbert's Syndrome where ≤3x the ULN is permitted
• Aspartate aminotransferase (AST)/ Alanine aminotransferase (ALT) ≤3 X ULN

You may not qualify if:

• History of another primary malignancy except for:
• Malignancy treated with curative intent and with no known active disease ≥2 years before the first dose of the study drug and of low potential risk for recurrence.
• Adequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease.
• Adequately treated carcinoma in situ without evidence of disease e.g., cervical cancer in situ, in-situ urinary bladder cancer, treated localized prostate cancer, and ductal carcinoma in-situ.
• Indolent hematological malignancies
• Current or prior use of immunosuppressive medication within 14 days before the first dose of cemiplimab, with the exceptions of intranasal, inhaled, topical steroids, or local steroid injections (e.g.intra articular injection), corticosteroids or systemic corticosteroids at physiological doses which are not to exceed 10 mg/day of prednisone or an equivalent corticosteroid, and steroids as premedication for hypersensitivity reactions (e.g., CT scan premedication).
• a. Any condition that requires ongoing/continuous corticosteroid therapy (\>10mg 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.
• \. Active or prior documented autoimmune or inflammatory disorders (including inflammatory bowel disease \[e.g., colitis or Crohn's disease systemic lupus erythematosus, sarcoidosis syndrome, or Wegener syndrome \[granulomatosis with polyangiitis, Graves' disease, rheumatoid arthritis, hypophysitis, uveitis, etc\]. No active diverticulitis within the previous 3 months. The following are exceptions to this criterion:
• Patients with vitiligo or alopecia
• Patients with endocrinopathies (such as hypothyroidism or type 1 diabetes (e.g., following Hashimoto syndrome) stable on hormone replacement, or psoriasis that does not require systemic treatment.
• Any chronic skin condition that does not require systemic therapy
• Patients with childhood asthma that has resolved 4. Uncontrolled, intercurrent illness including, but not limited to: ongoing or active infection requiring antibiotics (exception is a brief (≤10 days) course of antibiotics to be completed before initiation of treatment), symptomatic congestive heart failure, unstable angina pectoris, or psychiatric illness/social situations that would limit compliance with study requirements as determined by the Investigator.
• \. Interstitial lung disease (eg, idiopathic pulmonary fibrosis, organizing pneumonia) or active, noninfectious pneumonitis that requires immune-suppressive doses of glucocorticoids to assist with management. A history of radiation pneumonitis in the radiation field is permitted as long as pneumonitis is resolved ≥6 months prior to study treatment.
• \. Receipt of a live vaccine within 30 days of the planned start of study medication.
• Note: If a patient intends to receive a COVID-19 vaccine before the start of the study drug, participation in the study should be delayed at least 4 weeks after any COVID-19 vaccination. During the neoadjuvant treatment period, it is recommended to delay any COVID-19 vaccination or any other vaccination until patients have undergone radical surgery for the lung. A vaccine dose should not be administered less than 48 hours (ideally by at least one week) before or after study drug dosing.

Sponsors & Collaborators

• Weill Medical College of Cornell University: lead
• Regeneron Pharmaceuticals: collaborator

Study Sites (1)

Weill Cornell Medicine

New York, New York, 10065, United States

RECRUITING

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung; Lung Neoplasms; Bronchial Neoplasms; Carcinoma, Bronchogenic; Neoplasms

Interventions

cemiplimab; Platinum Compounds; Cisplatin; Pemetrexed; Gemcitabine; Carboplatin; Paclitaxel; Docetaxel; Radiosurgery

Condition Hierarchy (Ancestors)

Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Lung Diseases; Respiratory Tract Diseases; Bronchial Diseases

Intervention Hierarchy (Ancestors)

Inorganic Chemicals; Chlorine Compounds; Nitrogen Compounds; Guanine; Hypoxanthines; Purinones; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Glutamates; Amino Acids, Acidic; Amino Acids; Amino Acids, Peptides, and Proteins; Amino Acids, Dicarboxylic; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Coordination Complexes; Organic Chemicals; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Diterpenes; Terpenes; Radiotherapy; Therapeutics; Stereotaxic Techniques; Neurosurgical Procedures; Surgical Procedures, Operative; Investigative Techniques

Study Officials

• Nasser K Altorki, MD

  Weill Medical College of Cornell University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Julissa Murillo

CONTACT

2127463328; jum4020@med.cornell.edu

Julia Muuse

CONTACT

212-746-4528; jum4029@med.cornell.edu

Study Design

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

Study Record Dates

• First Submitted: September 30, 2024
• First Posted: October 2, 2024
• Study Start: February 21, 2025
• Primary Completion (Estimated): December 1, 2026
• Study Completion (Estimated): January 1, 2032
• Last Updated: April 21, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)