A Study of Cemiplimab Plus Chemotherapy Versus Cemiplimab Plus Chemotherapy Plus Other Cancer Treatments for Adult Patients With Operable Non-Small Cell Lung Cancer (NSCLC)

A Randomized Phase 2 Platform Study to Evaluate Cemiplimab Plus Chemotherapy Versus Cemiplimab Plus Chemotherapy Plus Other Cancer Treatments for the Perioperative Treatment of Patients With Resectable Non-Small Cell Lung Cancer

This study will enroll adult participants with early-stage (stage II-IIIB) non-small cell lung cancer (NSCLC) for whom surgery is planned, in the resectable NSCLC portion.

The aim of the resectable NSCLC portion is to find out whether an investigational treatment (consisting of the immunotherapy drug cemiplimab plus chemotherapy plus a third drug) works better than cemiplimab plus chemotherapy without the additional drug.

For each investigational arm, the available data will be reviewed to decide whether safety testing with chemotherapy is needed before moving the treatment combination to the main resectable NSCLC portion of the study. If safety testing with chemotherapy is required, adult participants whose tumour has spread to other organs or cannot be removed by surgery, will be enrolled in the unresectable/metastatic NSCLC portion of the study called the "safety lead-in."

The aim of the unresectable/metastatic NSCLC safety lead-in portion is to evaluate the safety of the combination of Cemiplimab, chemotherapy, and an additional drug in participants with unresectable or metastatic NSCLC.

For the resectable NSCLC portion, the study is also looking at several other research questions, including:

• What are the side effects associated with the investigational treatments in comparison to the control treatment
• Do the investigational treatments or the control treatment have an effect on the type of surgery that is performed
• How much of the study drug(s) are in the blood at a given time
• Does the body make antibodies against the study drug(s) (which could make the drug(s) less effective or could lead to side effects)

For the unresectable/metastatic NSCLC portion, the study is also looking at several other research questions, including:

• What are the side effects associated with the additional drug in combination with cemiplimab and chemotherapy
• How does the additional drug work in combination with cemiplimab and chemotherapy

Study Overview

• Status: Active, not recruiting
• Conditions: NSCLC; Non Small Cell Lung Cancer
• Intervention / Treatment: Drug: Marlotamig; Drug: Cemiplimab; Drug: Platinum-based chemotherapy; Drug: REGN10597

• Study Type: Interventional
• Enrollment (Estimated): 184
• Phase: Phase 2

Contacts and Locations

Study Locations

• Brazil
  • São Paulo, Brazil, 01323-903
    • Hospital Alemao Oswaldo Cruz
  • Espírito Santo
    • Cachoeiro de Itapemirim, Espírito Santo, Brazil, 29306014
      • Oncology Clinical Research Center
  • Minas Gerais
    • Belo Horizonte, Minas Gerais, Brazil, 30380-472
      • Instituto Mario Penna
    • Pouso Alegre, Minas Gerais, Brazil, 37554-238
      • Instituto Sul Mineiro De Oncologia LTDA
  • Pernambuco
    • Recife, Pernambuco, Brazil, 50070-902
      • Instituto de Medicina Integral Professor Fernando Figueira
  • Rio Grande do Norte
    • Natal, Rio Grande do Norte, Brazil, 59060-195
      • Liga Norte Riograndense Contra o Cancer
  • Rio Grande do Sul
    • Porto Alegre, Rio Grande do Sul, Brazil, 90610-000
      • Hospital Sao Lucas da PUCRS
    • Porto Alegre, Rio Grande do Sul, Brazil, 90110-270
      • Hospital Mae de Deus Integrated Oncology Center
  • Santa Catarina
    • Florianópolis, Santa Catarina, Brazil, 88020-210
      • Ynova Pesquisa Clinica
  • São Paulo
    • Sorocaba, São Paulo, Brazil, 18065-100
      • Unimed Sorocaba
    • São José do Rio Preto, São Paulo, Brazil, 15090-000
      • Fundacao Faculdade Regional de Medicina de Sao Jose do Rio Preto
• France
  • Bayonne, France, 64100
    • Clinique Belharra
  • Bayonne, France, 64100
    • Centre Hospitalier de la Cote Basque
  • Grenoble, France, 38330
    • CHU Grenoble Alpes
  • Montpellier, France, 34295
    • Montpellier Academic Hospital
  • Brittany Region
    • Rennes, Brittany Region, France, 35033
      • CHU Rennes
  • Var
    • Toulon, Var, France, 83055
      • Centre Hospitalier Intercommunal Toulon - CHITS
  • Île-de-France Region
    • Paris, Île-de-France Region, France, 75005
      • Institut Curie
• Germany
  • Aachen, Germany, 52074
    • University Hospital RWTH Aachen
  • Hesse
    • Kassel, Hesse, Germany, 34125
      • Klinikum Kassel GmbH, Hauttumorzentrum
  • Lower Saxony
    • Göttingen, Lower Saxony, Germany, 37083
      • University Medicine Gottingen
  • Saxony
    • Leipzig, Saxony, Germany, 04103
      • University of Leipzig
• Spain
  • Madrid, Spain, 28046
    • Hospital Universitario La Paz
  • Madrid, Spain, 28040
    • Hospital Universitario Clinico San Carlos
  • Madrid, Spain, 28033
    • MD Anderson Cancer Center
  • Madrid, Spain, 28050
    • Hospital Universitario HM Sanchinarro
  • Seville, Spain, 41013
    • Hospital Virgen del Rocio
  • Valencia, Spain, 46014
    • Consorci Hospital General Universitario de Valencia
  • Valencia, Spain, 46010
    • Hospital Clinico Universitario Valencia
  • Zaragoza, Spain, 50009
    • Hospital Clinico Lozano Blesa
  • Barcelona
    • Badalona, Barcelona, Spain, 08916
      • Catalan Instituye of Oncology Badalona
  • Cantabria
    • Santander, Cantabria, Spain, 39008
      • Hospital Valdecilla
  • Las Palmas
    • Las Palmas de Gran Canaria, Las Palmas, Spain, 35016
      • Hospital Universitario Insular de Gran Canaria
  • Navarre
    • Pamplona, Navarre, Spain, 31008
      • Clinica Universidad de Navarra
• Turkey (Türkiye)
  • Istanbul, Turkey (Türkiye), 34295
    • Florya Medical Park Hospital
• United States
  • California
    • Orange, California, United States, 92868
      • University of California Irvine
  • Illinois
    • Skokie, Illinois, United States, 60077
      • Orchard Healthcare Research Inc.
  • Michigan
    • Detroit, Michigan, United States, 48201
      • Karmanos Cancer Institute
    • Farmington Hills, Michigan, United States, 48334
      • Detroit Clinical Research Center
  • Ohio
    • Cincinnati, Ohio, United States, 45245
      • Oncology Hematology Care Clinical Trials LLC
  • Oregon
    • Portland, Oregon, United States, 97213
      • Providence Portland Medical Center
    • Portland, Oregon, United States, 97213
      • University Of Nebraska Medical Center
  • Rhode Island
    • Providence, Rhode Island, United States, 02903
      • Lifespan Cancer Institute
  • South Dakota
    • Watertown, South Dakota, United States, 57201
      • Prairie Lakes Healthcare System
  • Tennessee
    • Knoxville, Tennessee, United States, 37920
      • University of Tennessee Medical Center
    • Nashville, Tennessee, United States, 37203
      • Sarah Cannon Research Institute (SCRI) Oncology Partners
  • Virginia
    • Blacksburg, Virginia, United States, 24060
      • BRCC/Oncology & Hematology Associates of SW Virginia

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Neoadjuvant Resectable NSCLC General Key Inclusion Criteria:

1. Histologically confirmed stage II through IIIB (N2) NSCLC, that is considered resectable with curative intent, as described in the protocol
2. Measurable disease per Response Evaluation Criteria In Solid Tumors (RECIST) criteria version 1.1
3. Available formalin-fixed paraffin-embedded (FFPE) tumor sample blocks for submission, as described in the protocol
4. Eastern Cooperative Oncology Group Performance Status scale (ECOG PS) of 0 to 1
5. Adequate organ and bone marrow function, as described in the protocol

Arm Specific Inclusion Criteria:

Unresectable/Metastatic NSCLC Safety Lead-in - Arm 2:

1. Non-squamous or squamous histology NSCLC with stage IIIB or stage IIIC disease who are not candidates for surgical resection or definitive chemoradiation per investigator assessment or stage IV (metastatic disease), who received no prior systemic treatment for recurrent or metastatic NSCLC
2. Availability of an archival or on-trial FFPE tumor tissue sample
3. ECOG performance status of 0 or 1
4. Per investigator judgment, life expectancy of at least 3 months

Neoadjuvant Resectable NSCLC General Key Exclusion Criteria:

1. Any systemic anti-cancer therapy or radiotherapy for the current tumor, as described in the protocol
2. Presence of actionable oncogenic alterations in the tumor for which an approved targeted therapy is available or for which perioperative chemoimmunotherapy is not considered an appropriate standard of care treatment, as described in the protocol
3. Presence of grade≥ 2 peripheral neuropathy
4. Another malignancy that is progressing or requires active treatment, as described in the protocol

Arm Specific Exclusion Criteria:

Neoadjuvant Resectable NSCLC - Arm 1:

1. Grade ≥3 hypercalcemia, as defined in the protocol
2. Any central nervous system (CNS) pathology that could increase the risk of immune effector cell-associated neurotoxicity syndrome (ICANS), as described in the protocol
3. Has marked baseline prolongation of the time from the start of the Q wave to the end of the T wave in electrocardiogram (QT)/corrected QT interval (QTc) interval or risk factors for prolonged QTc, as described in the protocol

Unresectable/Metastatic NSCLC Safety Lead-in - Arm 2:

1. Untreated or active primary brain tumor, CNS metastases, leptomeningeal disease, or spinal cord compression, as described in the protocol
2. Presence of actionable oncogenic alterations in the tumor for which a chemotherapy plus programmed cell death protein 1 (PD1) inhibitor backbone is not the appropriate initial therapy as standard of care
3. Known allergy or hypersensitivity to any components of trial interventions
4. Any condition requiring ongoing/continuous corticosteroid therapy, as described in the protocol

Neoadjuvant Resectable NSCLC - Arm 2:

1. History of encephalitis, meningitis, organic brain disease, or uncontrolled seizures within 1 year prior to the first dose of trial interventions.

Note: Other protocol-defined Inclusion/Exclusion criteria apply.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Neoadjuvant Resectable NSCLC - Control Arm	Drug: Cemiplimab; Administered per the protocol; Other Names: REGN2810; LIBTAYO; Drug: Platinum-based chemotherapy; Administered per the protocol
Experimental: Neoadjuvant Resectable NSCLC - Arm 1	Drug: Marlotamig; Administered per the protocol; Other Names: REGN7075; Drug: Cemiplimab; Administered per the protocol; Other Names: REGN2810; LIBTAYO; Drug: Platinum-based chemotherapy; Administered per the protocol
Experimental: Unresectable/Metastatic NSCLC Safety Lead-in - Arm 2	Drug: Cemiplimab; Administered per the protocol; Other Names: REGN2810; LIBTAYO; Drug: Platinum-based chemotherapy; Administered per the protocol; Drug: REGN10597; Administered per the protocol; Other Names: PD-1-IL2Ra-IL2 immunotherapy
Experimental: Neoadjuvant Resectable NSCLC - Arm 2	Drug: Cemiplimab; Administered per the protocol; Other Names: REGN2810; LIBTAYO; Drug: Platinum-based chemotherapy; Administered per the protocol; Drug: REGN10597; Administered per the protocol; Other Names: PD-1-IL2Ra-IL2 immunotherapy

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Major Pathologic Response (MPR) rate as determined by central Blinded Independent Pathology Review (BIPR)		Up to 12 weeks
Occurrence of Treatment-Emergent Adverse Events (TEAEs)	Unresectable/Metastatic NSCLC Safety Lead-in - Arm 2	Up to 9 weeks
Occurrence of TEAEs leading to death	Unresectable/Metastatic NSCLC Safety Lead-in - Arm 2	Up to 9 weeks
Occurrence of TEAEs leading to treatment discontinuation	Unresectable/Metastatic NSCLC Safety Lead-in - Arm 2	Up to 9 weeks
Occurrence of Serious Adverse Events (SAEs)	Unresectable/Metastatic NSCLC Safety Lead-in - Arm 2	Up to 9 weeks
Occurrence of grade ≥3 laboratory abnormalities	Unresectable/Metastatic NSCLC Safety Lead-in - Arm 2 As assessed by the Common Terminology Criteria for Adverse Events (CTCAE) grading system version 5.0 (for all grades)	Up to 9 weeks
Number of participants unable to receive cemiplimab and chemotherapy for 2 consecutive cycles due to REGN10597-related toxicities during the first 3 cycles	Unresectable/Metastatic NSCLC Safety Lead-in - Arm 2	Up to 9 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Survival (OS)		Up to 5 years
Severity of TEAEs		Up to 76 weeks
Proportion of delayed surgeries due to TEAEs		Up to 76 weeks
Proportion of cancelled surgeries due to TEAEs		Up to 76 weeks
Pathologic Complete Response (pCR) rate as determined by central BIPR		Up to 12 weeks
Residual Viable Tumor (RVT) as determined by central BIPR		Up to 12 weeks
Event-Free Survival (EFS)		Up to 5 years
Objective Response by investigator assessment		Up to 9 weeks
Duration of Response (DoR) by investigator assessment	Unresectable/Metastatic NSCLC Safety Lead-in - Arm 2	Up to 2 years
Occurrence of TEAEs		Up to 76 weeks
Occurrence of TEAEs leading to death		Up to 76 weeks
Occurrence of TEAEs leading to treatment discontinuation		Up to 76 weeks
Occurrence of SAEs		Up to 76 weeks
Severity of SAEs		Up to 76 weeks
Occurrence of Adverse Events of Special Interest (AESIs)		Up to 76 weeks
Severity of AESIs		Up to 76 weeks
Occurrence of immune-mediated Adverse Events (imAEs)		Up to 76 weeks
Severity of imAEs		Up to 76 weeks
Occurrence of Infusion-Related Reactions (IRRs)		Up to 76 weeks
Severity of IRRs		Up to 76 weeks
Occurrence of grade ≥3 laboratory abnormalities	As assessed by the Common Terminology Criteria for Adverse Events (CTCAE) grading system version 5.0 (for all grades)	Up to 76 weeks
Occurrence of Anti-Drug Antibodies (ADAs) to cemiplimab		Up to 67 weeks
Magnitude of ADAs to cemiplimab		Up to 67 weeks
Occurrence of ADAs to marlotamig		Up to 67 weeks
Magnitude of ADAs to marlotamig		Up to 67 weeks
Occurrence of ADAs to REGN10597		Up to 67 weeks
Magnitude of ADAs to REGN10597		Up to 67 weeks

Collaborators and Investigators

• Sponsor: Regeneron Pharmaceuticals
• Investigators: Study Director: Clinical Trial Management, Regeneron Pharmaceuticals

Study record dates

Study Major Dates

• Study Start (Actual): November 18, 2024
• Primary Completion (Estimated): December 4, 2029
• Study Completion (Estimated): December 27, 2034

Study Registration Dates

• First Submitted: June 13, 2024
• First Submitted That Met QC Criteria: June 13, 2024
• First Posted (Actual): June 18, 2024

Study Record Updates

• Last Update Posted (Actual): November 3, 2026
• Last Update Submitted That Met QC Criteria: October 30, 2026
• Last Verified: October 1, 2026

More Information

Terms related to this study

• Keywords: NSCLC; Surgical resection; Early stage lung cancer; Carcinoma, Non-Small Cell Lung; Resectable NSCLC; Lung cancer surgery; Non-small cell lung carcinoma; Lung Carcinoma; Early-stage non-small cell lung cancer; Neoadjuvant NSCLC; Operable non-small cell lung cancer; Preoperative NSCLC
• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Respiratory Tract Diseases; Lung Diseases; Respiratory Tract Neoplasms; Thoracic Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Carcinoma, Non-Small-Cell Lung; Inorganic Chemicals; Platinum Compounds; cemiplimab
• Other Study ID Numbers: R2810-ONC-2268; 2023 (U.S. NIH Grant/Contract); 2023-509806-31-00 (Ctis)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

IPD Plan Description

All Individual Patient Data (IPD) that underlie publicly available results will be considered for sharing.

IPD Sharing Time Frame

When Regeneron has:

• received marketing authorization from major health authorities (e.g., FDA, European Medicines Agency (EMA), Pharmaceuticals and Medical Devices Agency (PMDA), etc.) for the product and indication or has globally discontinued development of the product for all indications on or after April 2020 and has no plans for future development
• made the study results publicly available (e.g., scientific publication, scientific conference, clinical trial registry)
• the legal authority to share the data, and
• ensured the ability to protect participant privacy

IPD Sharing Access Criteria

Qualified researchers can submit a proposal for access to individual patient or aggregate level data from a Regeneron-sponsored clinical trial through Vivli. Regeneron's Independent Research Request Evaluation Criteria can be found at: https://www.regeneron.com/sites/default/files/Regeneron-External-Data-Sharing-Policy-and-Independent-Research-Request-Evaluation-Criteria.pdf

• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; ANALYTIC_CODE; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No