Safety and Efficacy of Intravenous Cemiplimab Plus BNT116 Versus Cemiplimab Alone in Advanced Non-Small Cell Lung Cancer in Adult Participants With PD-L1 ≥ 50%

A Phase 2 Study of Cemiplimab (Anti-PD-1 Antibody) in Combination With BNT116 (FixVac Lung) Versus Cemiplimab Monotherapy in First-Line Treatment of Patients With Advanced Non-Small Cell Lung Cancer (NSCLC) With Tumors Expressing PD-L1 ≥50%

The study is researching an investigational drug, called BNT116, in combination with cemiplimab. BNT116 and cemiplimab will each be called a "study drug", and together be called "study drugs" in this form. The study is focused on patients who have advanced non-small cell lung cancer (NSCLC).

The aims of the study are to see how safe and tolerable BNT116 is in combination with cemiplimab and to see how effective BNT116 in combination with cemiplimab is compared to cemiplimab by itself at treating your cancer.

The study is looking at several other research questions, including:

• What side effects may happen from receiving the study drugs
• How much study drug is in your blood at different times
• Whether the body makes antibodies against the study drug(s) (which could make the drug less effective or could lead to side effects)

Study Overview

• Status: Recruiting
• Conditions: Advanced Non-Small Cell Lung Cancer
• Intervention / Treatment: Drug: BNT116; Drug: Cemiplimab

• Study Type: Interventional
• Enrollment (Estimated): 100
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Clinical Trials Administrator; Phone Number: 844-734-6643; Email: clinicaltrials@regeneron.com

Study Locations

• Georgia
  • Batumi, Georgia, 6000
    • Recruiting
    • LTD High Technology Hospital Medcenter
  • Tbilisi, Georgia, 0144
    • Recruiting
    • Ltd Tbilisi State Medical University and Ingorokva High Medical Technology University Clinic
  • Tbilisi, Georgia, 0112
    • Recruiting
    • LLC Todua Clinic
  • Tbilisi, Georgia, 0162
    • Recruiting
    • Ltd New Hospitals
• Germany
  • Frankfurt am Main, Germany, 60590
    • Not yet recruiting
    • Klinikum der Johann Wolfgang Goethe-Universitaet Frankfurt
  • Giessen, Germany, 80336
    • Not yet recruiting
    • Universitaetsklinikum Giessen Und Marburg Gmbh Standort Giessen
  • Halle, Germany, 6120
    • Not yet recruiting
    • Krankenhaus Martha-Maria Halle-Doelau gGmbH
  • Kempten, Germany, 87439
    • Not yet recruiting
    • Klinikverbund Kempten-Oberallgäu
  • Muenchen, Germany, 81925
    • Not yet recruiting
    • Staedtisches Klinikum Muenchen Bogenhausen
• Korea, Republic of
  • Goyang, Korea, Republic of, 10408
    • Not yet recruiting
    • National Cancer Center Korea
  • Seoul, Korea, Republic of, 05505
    • Not yet recruiting
    • Asan Medical Center
  • Seoul, Korea, Republic of, 03080
    • Not yet recruiting
    • Seoul National University Hospital
  • Seoul, Korea, Republic of, 6351
    • Not yet recruiting
    • Samsung Medical Center
  • Seoul, Korea, Republic of, 3722
    • Not yet recruiting
    • Yonsei Severance
  • Gyeonggi
    • Seoul, Gyeonggi, Korea, Republic of, 2841
      • Not yet recruiting
      • Korea University Anam Hospital
  • Jeonnam
    • Hwasun, Jeonnam, Korea, Republic of, 58128
      • Not yet recruiting
      • Chonnam National University Hwasun Hospital
• Spain
  • Badalona, Spain, 08916
    • Not yet recruiting
    • Catalan Institute of Oncology Badalona
  • Barcelona, Spain, 08243
    • Not yet recruiting
    • Althaia, Xarxa Assistencial Universitària Manresa
  • Castello, Spain, 12002
    • Recruiting
    • Consorcio Hospitalario Provincial de Castellon
  • Madrid, Spain, 28040
    • Not yet recruiting
    • Hospital Universitario Fundacion Jimenez Diaz
  • Madrid, Spain, 28027
    • Recruiting
    • Clinica Universidad de Navarra - Madrid
  • Madrid, Spain, 28007
    • Not yet recruiting
    • Hospital General Universitario Gregorio Maranon (HGUGM)
  • Malaga, Spain, 29010
    • Not yet recruiting
    • Hospital Regional Universitario de Malaga
  • Malaga, Spain, 29010
    • Recruiting
    • Hospital Universitario Virgen del Rocio
  • Pamplona, Spain, 31008
    • Recruiting
    • Clinica Universidad de Navarra
  • Valencia, Spain, 46026
    • Not yet recruiting
    • Hospital Universitari i Politecnic La Fe de Valencia
  • Valencia, Spain, 46009
    • Not yet recruiting
    • Instituto Valenciano de Oncología
• Taiwan
  • Kaohsiung, Taiwan, 807
    • Not yet recruiting
    • Chung-Ho Memorial Hospital
  • Kaohsiung, Taiwan, 807
    • Not yet recruiting
    • Kaohsiung Medical University - Chung-Ho Memorial Hospital
  • New Taipei City, Taiwan, 23561
    • Not yet recruiting
    • Taipei Medical University - Shuang Ho Hospital
  • Taipei, Taiwan, 100
    • Not yet recruiting
    • National Taiwan University Hosptial
  • Taipei City, Taiwan, 114
    • Not yet recruiting
    • Tri-Service General Hospital
• Turkey
  • Ankara, Turkey, 06800
    • Not yet recruiting
    • Ankara Bilkent Sehir Hastanesi
  • Ankara, Turkey, 06680
    • Not yet recruiting
    • Liv Hospital
  • Ankara, Turkey, 06100
    • Not yet recruiting
    • Sbu Dr. A.Y. Ankara Onkoloji Suam
  • Istanbul, Turkey, 34093
    • Not yet recruiting
    • Bezmialem Foundation University Medical Faculty
  • Istanbul, Turkey, 34295
    • Not yet recruiting
    • IAU VM Medical Park Hospital
  • Istanbul, Turkey, 81450
    • Not yet recruiting
    • Istanbul Medeniyet University Prof. Dr. Suleyman Yalcin Sehir Hospital
  • Izmir, Turkey, 35000
    • Not yet recruiting
    • Izmir Medicalpark Hospital
  • Seyhan, Turkey, 01140
    • Not yet recruiting
    • Medical Park Seyhan Hospital
  • Bahcelievler
    • Ankara, Bahcelievler, Turkey, 06490
      • Not yet recruiting
      • Baskent University Faculty of Medicine Ankara Hospital
  • Istanbul
    • Kadikoy, Istanbul, Turkey, 34718
      • Not yet recruiting
      • Yeditepe University Kosuyolu Hospital
  • Izmir
    • Bornova, Izmir, Turkey, 35040
      • Not yet recruiting
      • Ege University Medical Faculty
• United States
  • California
    • Los Angeles, California, United States, 90033
      • Recruiting
      • The Oncology Institute of Hope and Innovation
    • Orange, California, United States, 92697
      • Not yet recruiting
      • University of California Irvine
    • Santa Monica, California, United States, 90095
      • Recruiting
      • UCLA Medical Center
  • Kentucky
    • Louisville, Kentucky, United States, 40202
      • Recruiting
      • Norton Cancer Institute, Downtown
  • Massachusetts
    • Boston, Massachusetts, United States, 02215
      • Recruiting
      • Dana Farber/Harvard Cancer Center
  • New Mexico
    • Farmington, New Mexico, United States, 87401
      • Recruiting
      • San Juan Oncology Associates
  • New York
    • New York, New York, United States, 10065
      • Not yet recruiting
      • Weill Cornell Medical College
  • North Carolina
    • Charlotte, North Carolina, United States, 28204
      • Recruiting
      • Oncology Specialists of Charlotte Pa
    • Pinehurst, North Carolina, United States, 28374
      • Recruiting
      • FirstHealth of the Carolinas, Inc.
  • Texas
    • Houston, Texas, United States, 77090
      • Completed
      • Millenium Research & Clinical Development
  • Virginia
    • Fairfax, Virginia, United States, 22031
      • Recruiting
      • Virginia Cancer Specialists
  • Washington
    • Tacoma, Washington, United States, 98405
      • Recruiting
      • Northwest Medical Specialties, PLLC

Participation Criteria

Eligibility Criteria

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

Description

Key Inclusion Criteria

1. Participants with 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-study obtained formalin-fixed, paraffin-embedded tumor tissue sample as defined in the protocol.
3. Expression of Programmed cell death ligand-1 (PD-L1) in ≥50% of tumor cells stained using the VENTANA PD-L1 (SP263) Assay as performed by a central laboratory
4. Participants must have at least 1 radiographically measurable lesion by computerized tomography (CT) or magnetic resonance imaging (MRI) per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1) criteria
5. Eastern Cooperative Oncology Group (ECOG) performance status ≤1

Key Exclusion Criteria

1. Participants who have never smoked, defined as smoking ≤100 cigarettes in a lifetime
2. Active or untreated brain metastases or spinal cord compression. Participants are eligible if central nervous system (CNS) metastases are adequately treated and patients have neurologically returned to baseline (except for residual signs or symptoms related to the CNS treatment) for at least 2 weeks prior to enrollment
3. Participants with tumors tested positive for epidermal growth factor receptor (EGFR) gene mutations, anaplastic lymphoma kinase (ALK) gene translocations, or C-ros oncogene receptor tyrosine kinase 1 (ROS1) fusions
4. Encephalitis, meningitis, or uncontrolled seizures in the year prior to enrollment
5. Participants with history of interstitial lung disease (eg, idiopathic pulmonary fibrosis or organizing pneumonia), of active, noninfectious pneumonitis that required immune-suppressive doses of glucocorticoids to assist with management, or of pneumonitis within the last 5 years
6. Prior splenectomy
7. Uncontrolled infection with human immunodeficiency virus (HIV), HBV or hepatitis C infection (HCV); or diagnosis of immunodeficiency as defined in the protocol
8. Ongoing or recent (within 2 years) evidence of significant autoimmune disease that required treatment with systemic immunosuppressive treatments, which may suggest risk of immune-related treatment-emergent adverse events (imTEAEs)
9. Participants requiring corticosteroid therapy (>5 mg prednisone/day or equivalent) within 14 days of randomization
10. Another malignancy that is progressing or requires treatment, with the exception of non-melanomatous skin cancer that has undergone potentially curative therapy, in situ cervical carcinoma, or any other localized tumor that has been treated, and the participant is deemed to be in complete remission for at least 2 years prior to enrollment, and no additional therapy is required during the study period
11. Documented or suspected ongoing severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection as defined in the protocol

12. Patients who have received prior systemic therapies for NSCLC are excluded with the exception of the following:

    1. Adjuvant or neoadjuvant platinum-based doublet chemotherapy (after surgery and/or radiation therapy) if recurrent or metastatic disease develops more than 6 months after completing therapy as long as toxicities have resolved to CTCAE grade ≤1 or baseline with the exception of alopecia and peripheral neuropathy.
    2. Anti-PD-(L)1 with or without LAG-3 as an adjuvant or neoadjuvant therapy as long as the last dose is >12 months prior to enrollment.
    3. Prior exposure to other immunomodulatory or vaccine therapies as an adjuvant or neoadjuvant therapy such as anti-cytotoxic T lymphocyte-associated antigen (anti-CTLA-4) antibodies as long as the last dose is >6 months prior to enrollment
13. History or current evidence of significant cardiovascular disease including, myocarditis, congestive heart failure (as defined by New York Heart Association Functional Classification III and IV), unstable angina, serious uncontrolled arrhythmia, and myocardial infarction 6 months prior to study enrollment.
14. Hypersensitivity to cemiplimab or BNT116 or any of their excipients, or contraindicated to cemiplimab per approved local labeling.
15. Patients treated with immunostimulatory agents that may influence the efficacy of the investigational medicinal products (IMPs) are not allowed if they received such agents within 6 weeks or five halve lives of the drug.

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

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Phase 2: Cemiplimab; Arm A: Cemiplimab is administered by IV infusion Q3W	Drug: Cemiplimab; Cemiplimab is administered Q3W by IV infusion; Other Names: REGN2810; Libtayo
Experimental: Phase 2: BNT116 + Cemiplimab; Arm B: BNT116 is administered by IV injection. Cemiplimab is administered by IV infusion Q3W.	Drug: BNT116; BNT116 is administered by IV injection.; Drug: Cemiplimab; Cemiplimab is administered Q3W by IV infusion; Other Names: REGN2810; Libtayo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective response rate (ORR) as assessed by blinded independent review committee (BIRC) using Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1)	Proportion of patients with a best overall response of confirmed complete response (CR) or partial response (PR)	Up to 136 weeks from randomization

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
ORR by investigator assessment	Proportion of patients with a best overall response of confirmed CR or PR	Up to 136 weeks from randomization
Duration of Response (DOR) as assessed by BIRC using RECIST 1.1	The time from first response of CR or PR to first radiographic progression or death due to any cause for patients with confirmed CR or PR	Up to 3 years from last patient randomized
DOR by investigator assessment	The time from first response of CR or PR to first radiographic progression or death due to any cause for patients with confirmed CR or PR	Up to 3 years from last patient randomized
Progression Free Survival (PFS) as assessed by BIRC using RECIST 1.1	The time from randomization to the date of the first radiographic progression or death due to any cause, whichever occurred earlier	Up to 3 years from last patient randomized
PFS by investigator assessment	The time from randomization to the date of the first radiographic progression or death due to any cause, whichever occurred earlier	Up to 3 years from last patient randomized
Overall Survival (OS)	The time from enrollment to the date of death due to any cause	Up to 3 years from last patient randomized
Incidence of treatment-emergent adverse events (TEAEs)	A TEAE is any untoward medical occurrence in a patient or clinical investigation participant administered a pharmaceutical product, which does not necessarily have a causal relationship with this treatment.	Up to 3 years
Incidences of serious adverse events (SAEs)	An SAE is any untoward medical occurrence that at any dose: Results in death - includes all deaths, even those that appear to be completely unrelated to study drug (eg, a car accident in which a patient is a passenger); Is life-threatening; Requires in-patient hospitalization or prolongation of existing hospitalization; Results in persistent or significant disability/incapacity; Is a congenital anomaly/birth defect; Is an important medical event	Up to 3 years
Incidences of deaths		Up to 3 years
Incidences of laboratory abnormalities	According to Common Terminology Criteria for Adverse Events (CTCAE) v5.0 Causality grading system (≥ Grade 3 or higher)	Up to 3 years

Collaborators and Investigators

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

Study record dates

Study Major Dates

• Study Start (Actual): April 21, 2023
• Primary Completion (Estimated): March 2, 2027
• Study Completion (Estimated): June 7, 2027

Study Registration Dates

• First Submitted: September 23, 2022
• First Submitted That Met QC Criteria: September 23, 2022
• First Posted (Actual): September 28, 2022

Study Record Updates

• Last Update Posted (Actual): April 23, 2024
• Last Update Submitted That Met QC Criteria: April 22, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Keywords: Immunotherapy; Cancer Vaccine; Programmed cell death ligand-1 (PD-L1) monoclonal antibody; Treatment naïve Advanced Non-Small Cell Lung Cancer (NSCLC); EMPOWERVAX Lung 1
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Neoplasms; Lung Diseases; Neoplasms by Site; Respiratory Tract Neoplasms; Thoracic Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Carcinoma, Non-Small-Cell Lung; Antineoplastic Agents; Antineoplastic Agents, Immunological; Cemiplimab
• Other Study ID Numbers: R2810-ONC-2045; 2021-006901-31 (EudraCT Number); 2023-503221-19-00 (Registry Identifier: EUCT)

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: Individual anonymized participant data will be considered for sharing once the indication has been approved by a regulatory body, if there is legal authority to share the data and there is not a reasonable likelihood of participant re-identification.
• IPD Sharing Access Criteria: Qualified researchers may request access to anonymized patient level data or aggregate study data 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, has the legal authority to share the data, and has made the study results publicly available (eg, scientific publication, scientific conference, clinical trial registry).
• 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