Clinical trial NCT05557591: A Trial to Learn How the Cancer Vaccine BNT116 in Combination With Cemiplimab Works and How Safe the Combination is in Adults With Advanced Non-small Cell Lung Cancer (EMPOWERVAX Lung 1)
Official title: 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%
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Advanced Non-Small Cell Lung Cancer
Keywords: Cancer Vaccine
Immunotherapy
Programmed cell death ligand-1 (PD-L1) monoclonal antibody
Treatment naïve Advanced Non-Small Cell Lung Cancer (NSCLC)
EMPOWERVAX Lung 1
Lead sponsor: Regeneron Pharmaceuticals
Sponsor class: INDUSTRY
Collaborators: name: BioNTech SE
First posted: 2022-09-28
Enrollment: 100
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This 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". The study is focused on patients who have advanced non-small cell lung cancer (NSCLC).

The aims of this 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 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 the 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)


Eligibility criteria: 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) ≥50%, as described in the protocol.
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, except for 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 except for 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 if toxicities have resolved to CTCAE grade ≤1 or baseline except for 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 if 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

Primary outcomes:
measure: 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)
timeFrame: Up to 136 weeks from randomization
Secondary outcomes:
measure: ORR by investigator assessment
timeFrame: Up to 136 weeks from randomization
measure: Duration of Response (DOR) as assessed by BIRC using RECIST 1.1
timeFrame: Up to 3 years from last patient randomized
measure: DOR by investigator assessment
timeFrame: Up to 3 years from last patient randomized
measure: Progression Free Survival (PFS) as assessed by BIRC using RECIST 1.1
timeFrame: Up to 3 years from last patient randomized
measure: PFS by investigator assessment
timeFrame: Up to 3 years from last patient randomized
measure: Overall Survival (OS)
timeFrame: Up to 3 years from last patient randomized
measure: Incidence of treatment-emergent adverse events (TEAEs)
timeFrame: Up to 3 years
measure: Incidences of serious adverse events (SAEs)
timeFrame: Up to 3 years
measure: Incidences of deaths
timeFrame: Up to 3 years
measure: Incidences of laboratory abnormalities
timeFrame: Up to 3 years
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: The Oncology Institute of Hope and Innovation
state: California
city: Orange
country: United States
facility: University of California Irvine
state: California
city: Santa Monica
country: United States
facility: UCLA Medical Center
state: California
city: Louisville
country: United States
facility: Norton Cancer Institute, Downtown
state: Kentucky
city: Boston
country: United States
facility: Dana Farber/Harvard Cancer Center
state: Massachusetts
city: Farmington
country: United States
facility: San Juan Oncology Associates
state: New Mexico
city: New York
country: United States
facility: Weill Cornell Medicine
state: New York
city: Charlotte
country: United States
facility: Oncology Specialists of Charlotte PA
state: North Carolina
city: Pinehurst
country: United States
facility: FirstHealth of the Carolinas Outpatient Cancer Center
state: North Carolina
city: Houston
country: United States
facility: Millenium Research & Clinical Development
state: Texas
city: Fairfax
country: United States
facility: Virginia Cancer Specialists
state: Virginia
city: Tacoma
country: United States
facility: Northwest Medical Specialties, PLLC
state: Washington
city: Batumi
country: Georgia
facility: LTD High Technology Hospital Medcenter
city: Tbilisi
country: Georgia
facility: LLC Todua Clinic
city: Tbilisi
country: Georgia
facility: LTD Tbilisi State Medical University and Ingorokva High Medical Technology University Clinic
city: Tbilisi
country: Georgia
facility: LTD New Hospitals
city: Tbilisi
country: Georgia
facility: LTD Cancer Research Centre
city: Tbilisi
country: Georgia
facility: Caucasus Medical Centre
city: Munchen
country: Germany
facility: Staedtisches Klinikum Muenchen Bogenhausen
state: Bavaria
city: Frankfurt
country: Germany
facility: Klinikum der Johann Wolfgang Goethe-Universitaet Frankfurt
city: Giessen
country: Germany
facility: Universitaetsklinikum Giessen Und Marburg Gmbh Standort Giessen
city: Halle
country: Germany
facility: Krankenhaus Martha-Maria Halle-Doelau gGmbH
city: Kempten
country: Germany
facility: Klinikverbund Kempten-Oberallgäu
city: Seoul
country: Korea, Republic of
facility: Korea University Anam Hospital
state: Gyeonggi
city: Hwasun
country: Korea, Republic of
facility: Chonnam National University Hwasun Hospital
state: Jeonnam
city: Goyang
country: Korea, Republic of
facility: National Cancer Center Korea
city: Seoul
country: Korea, Republic of
facility: Asan Medical Center
city: Seoul
country: Korea, Republic of
facility: Yonsei Severance
city: Seoul
country: Korea, Republic of
facility: Samsung Medical Center
city: Seoul
country: Korea, Republic of
facility: Seoul National University Hospital
city: Badalona
country: Spain
facility: Catalan Institute of Oncology Badalona
state: Barcelona
city: Manresa
country: Spain
facility: Althaia Xarxa Assistencial Universitaria Manresa
state: Barcelona
city: Castello de la Plana
country: Spain
facility: Consorcio Hospitalario Provincial de Castellon
state: Castellon
city: Madrid
country: Spain
facility: Hospital General Universitario Gregorio Marañon (HGUGM)
city: Madrid
country: Spain
facility: Clinica Universidad de Navarra - Madrid
city: Madrid
country: Spain
facility: Hospital Universitario Fundacion Jimenez Diaz
city: Malaga
country: Spain
facility: Hospital Regional Universitario de Malaga
city: Malaga
country: Spain
facility: Hospital Universitario Virgen del Rocio
city: Pamplona
country: Spain
facility: Clinica Universidad de Navarra
city: Valencia
country: Spain
facility: Instituto Valenciano de Oncologia
city: Valencia
country: Spain
facility: Hospital Universitari i Politecnic La Fe de Valencia
city: Kaohsiung
country: Taiwan
facility: Kaohsiung Medical University - Chung-Ho Memorial Hospital
city: New Taipei City
country: Taiwan
facility: Taipei Tzu Chi Hospital
city: New Taipei City
country: Taiwan
facility: Taipei Medical University - Shuang Ho Hospital
city: Taipei City
country: Taiwan
facility: Tri-Service General Hospital
city: Taipei
country: Taiwan
facility: National Taiwan University Hospital
city: Yuregir
country: Turkey
facility: Baskent University
state: Adana
city: Kadikoy
country: Turkey
facility: Yeditepe University Kosuyolu Hospital
state: Istanbul
city: Bornova
country: Turkey
facility: Ege University Faculty of Medicine
state: Izmir
city: Adana
country: Turkey
facility: Adana Medical Park Seyhan Hospital
state: Seyhan
city: Ankara
country: Turkey
facility: Ozel Liv Hospital
city: Ankara
country: Turkey
facility: Sbu Doctor Abdurrahman Yurtaslan Ankara Onkoloji Suam
city: Ankara
country: Turkey
facility: Ankara Bilkent Sehir Hastanesi
city: Istanbul
country: Turkey
facility: Bezmialem Foundation University Medical Faculty
city: Istanbul
country: Turkey
facility: IAU VM Medical Park Hospital
city: Istanbul
country: Turkey
facility: Istanbul Medeniyet University Prof. Dr. Suleyman Yalcin Sehir Hospital
city: Izmir
country: Turkey
facility: Izmir Economy University Medical Point Hospital
Study officials:
affiliation: Regeneron Pharmaceuticals
name: Clinical Trial Management
role: STUDY_DIRECTOR
References: