Clinical trial NCT05785767: A Study to Learn if a Combination of Fianlimab and Cemiplimab Versus Cemiplimab Alone is More Effective for Adult Participants With Advanced Non-Small Cell Lung Cancer (NSCLC)
Official title: A Randomized, Double-Blind Phase 2/3 Study of Fianlimab (Anti-LAG-3 Antibody) in Combination With Cemiplimab (Anti-PD-1 Antibody) 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
PHASE3
Conditions: Advanced Non-Small Cell Lung Cancer
Keywords: Treatment naïve
NSCLC
Lead sponsor: Regeneron Pharmaceuticals
Sponsor class: INDUSTRY
First posted: 2023-03-27
Enrollment: 850
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 experimental drug called fianlimab (also called REGN3767), combined with a medication called cemiplimab (also called REGN2810), individually called a "study drug" or collectively called "study drugs". The study is focused on patients who have advanced non-small cell lung cancer (NSCLC).

The aim of the study is to see how effective the combination of fianlimab and cemiplimab is in treating advanced NSCLC, in comparison with cemiplimab by itself.

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

* What side effects may happen from taking the study drugs
* How much study drug is in your blood at different times
* Whether the body makes antibodies against the study drugs (which could make the drug less effective or could lead to side effects)
* How administering the study drugs might improve your quality of life


Eligibility criteria: Key Inclusion Criteria:

1. Patients 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 formalin-fixed, paraffin-embedded (FFPE) tumor tissue sample, without intervening therapy between biopsy collection and screening as described in the protocol
3. For enrollment in phase 2, patients should have PD-L1 levels ≥ 50%, as determined by a College of American Pathologists (CAP)/Clinical Laboratory Improvement Amendments (CLIA) (or equivalently licensed, according to local regulations) accredited laboratory, as described in the protocol. For enrollment in phase 3, patients should have expression of programmed cell death ligand-1 (PD-L1) in ≥50% of tumor cells stained using an assay performed by a central laboratory, as described in the protocol.
4. At least 1 radiographically measurable lesion by computed tomography (CT) or magnetic resonance imaging (MRI) per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1) criteria. Target lesions may be located in a previously irradiated field if there is documented (radiographic) disease progression in that site.
5. Eastern Cooperative Oncology Group (ECOG) performance status of ≤1.
6. Adequate organ and bone marrow function, as described in the protocol.

Key Exclusion Criteria:

1. Patients who have never smoked, defined as smoking ≤100 cigarettes in a lifetime.
2. Active or untreated brain metastases or spinal cord compression. Patients 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. Patients must be off (immunosuppressive doses of) corticosteroid therapy.
3. Patients with tumors tested positive for actionable epidermal growth factor receptor (EGFR) gene mutations, anaplastic lymphoma kinase (ALK) gene translocations, or c-ros oncogene 1 (ROS1) fusions, as described in the protocol.
4. Encephalitis, meningitis, or uncontrolled seizures in the year prior to enrollment.
5. 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. A history of radiation pneumonitis in the radiation field is permitted as long as pneumonitis resolved ≥6 months prior to enrollment.
6. Known primary immunodeficiencies, either cellular (eg, DiGeorge syndrome, T-cell-negative severe combined immunodeficiency \[SCID\]) or combined T- and B-cell immunodeficiencies (eg, T- and B-cell negative SCID, Wiskott Aldrich syndrome, ataxia telangiectasia, common variable immunodeficiency).
7. Ongoing or recent (within 2 years) evidence of significant autoimmune disease that required treatment with systemic immunosuppressive treatments, which may suggest risk of immune-mediated treatment-emergent adverse events (imTEAEs). Patients with uncontrolled type 1 diabetes mellitus or with uncontrolled adrenal insufficiency are excluded. The following are not exclusionary: vitiligo, childhood asthma that has resolved, residual hypothyroidism that required only hormone replacement, or psoriasis that does not require systemic treatment.
8. Patients with a condition requiring corticosteroid therapy (\>10 mg prednisone/day or equivalent) within 14 days of randomization. Physiologic replacement doses are allowed even if they are \>10 mg of prednisone/day or equivalent, as long as they are not being administered for immunosuppressive intent. Patients with clinically relevant systemic immune suppression within the last 3 months before trial enrollment are excluded. Inhaled or topical steroids are permitted, provided that they are not for treatment of an autoimmune disorder.
9. Patients who have received prior systemic therapies 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, Cytotoxic T-lymphocyte-associated protein 4 (anti-CTLA-4) antibodies as long as the last dose is \>6 months prior to enrollment. Immune-mediated AEs must be resolved to CTCAE grade ≤1 or baseline by the time of enrollment. Endocrine immune-mediated AEs controlled with hormonal or other non-immunosuppressive therapies without resolution prior to enrollment are allowed.

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

Primary outcomes:
measure: Objective response rate (ORR) as assessed by blinded independent central review (BICR), using Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1)
timeFrame: Up to 136 weeks
measure: Overall survival (OS)
timeFrame: Up to 5 years
Secondary outcomes:
measure: Incidence of treatment-emergent adverse events (TEAEs)
timeFrame: Up to 136 weeks
measure: Incidence of treatment-related TEAEs
timeFrame: Up to 136 weeks
measure: Incidence of serious adverse events (SAEs)
timeFrame: Up to 136 weeks
measure: Incidence of adverse events of special interest (AESIs)
timeFrame: Up to 136 weeks
measure: Incidence of immune-mediated adverse events (imAEs)
timeFrame: Up to 136 weeks
measure: Occurrence of interruption of study drug(s) due to TEAEs
timeFrame: Up to 136 weeks
measure: Occurrence of discontinuation of study drug(s) due to TEAEs
timeFrame: Up to 136 weeks
measure: Occurrence of interruption of study drug(s) due to AESIs
timeFrame: Up to 136 weeks
measure: Occurrence of discontinuation of study drug(s) due to AESIs
timeFrame: Up to 136 weeks
measure: Occurrence of interruption of study drug(s) due to imAEs
timeFrame: Up to 136 weeks
measure: Occurrence of discontinuation of study drug(s) due to imAEs
timeFrame: Up to 136 weeks
measure: Incidence of deaths due to TEAE
timeFrame: Up to 136 weeks
measure: Incidence of grade 3 to 4 laboratory abnormalities
timeFrame: Up to 136 weeks
measure: ORR by investigator assessment, using RECIST 1.1
timeFrame: Up to 136 weeks
measure: Disease control rate (DCR) by BICR
timeFrame: Up to 136 weeks
measure: DCR by investigator assessment
timeFrame: Up to 136 weeks
measure: Time to tumor response (TTR) by BICR
timeFrame: Up to 136 weeks
measure: TTR by investigator assessment
timeFrame: Up to 136 weeks
measure: Duration of response (DOR) by BICR
timeFrame: Up to 5 years
measure: DOR by investigator assessment
timeFrame: Up to 5 years
measure: Progression free survival (PFS) by BICR
timeFrame: Up to 5 years
measure: PFS by investigator assessment
timeFrame: Up to 5 years
measure: Overall survival (OS)
timeFrame: Up to 5 years
measure: Change from baseline in patient-reported global health status/quality of life (GHS/QoL) per European Organization for Research and Treatment of Cancer Quality of Life Core Questionnaire (EORTC QLQ-C30)
timeFrame: Up to 5 years
measure: Change from baseline in patient-reported physical functioning per EORTC QLQ-C30
timeFrame: Up to 5 years
measure: Change from baseline in patient-reported chest pain per European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Lung Cancer (EORTC QLQ-LC13)
timeFrame: Up to 5 years
measure: Change from baseline in patient-reported dyspnea per EORTC QLQ-LC13
timeFrame: Up to 5 years
measure: Change from baseline in patient-reported cough per EORTC QLQ-LC13
timeFrame: Up to 5 years
measure: Time until definitive deterioration in patient-reported global health status/QoL per EORTC QLQ-C30
timeFrame: Up to 5 years
measure: Time until definitive deterioration in patient-reported physical functioning per EORTC QLQ-C30
timeFrame: Up to 5 years
measure: Time until definitive deterioration in patient-reported chest pain per EORTC QLQ-LC13
timeFrame: Up to 5 years
measure: Time until definitive deterioration in patient-reported dyspnea per EORTC QLQ-LC13
timeFrame: Up to 5 years
measure: Time until definitive deterioration in patient-reported cough per EORTC QLQ-LC13
timeFrame: Up to 5 years
measure: Time until definitive deterioration in patient-reported composite of chest pain, dyspnea and cough per EORTC QLQ-LC13
timeFrame: Up to 5 years
measure: Change from baseline in patient-reported general health status per EuroQoL-5 Dimensions, 5-level Questionnaire-Visual Analogue Score (EQ-5D-5L VAS)
timeFrame: Up to 5 years
measure: Change from baseline in patient-reported severity with usual or daily activities due to fatigue per the Patient Reported Outcomes for Common Terminology Criteria for Adverse Events (PRO-CTCAE).
timeFrame: Up to 5 years
measure: Change from baseline in patient-reported interference with usual or daily activities due to fatigue per the Patient Reported Outcomes for Common Terminology Criteria for Adverse Events (PRO-CTCAE).
timeFrame: Up to 5 years
measure: Concentrations of cemiplimab in serum
timeFrame: Up to 136 weeks
measure: Concentrations of fianlimab in serum
timeFrame: Up to 136 weeks
measure: Immunogenicity, as measured by anti-drug antibodies (ADA) to fianlimab
timeFrame: Up to 136 weeks
measure: Immunogenicity, as measured by ADA to cemiplimab
timeFrame: Up to 136 weeks
measure: Immunogenicity, as measured by neutralizing antibodies (NAb) to fianlimab
timeFrame: Up to 136 weeks
measure: Immunogenicity, as measured by NAb to cemiplimab
timeFrame: Up to 136 weeks
Other outcomes:
Locations:
city: Tucson
country: United States
facility: Arizona Clinical Research Center
state: Arizona
city: Yuma
country: United States
facility: Yuma Regional Medical Center
state: Arizona
city: Rancho Mirage
country: United States
facility: Desert Hematology Oncology Medical Group Incorporated
state: California
city: Redlands
country: United States
facility: Emad Ibrahim, MD, Inc.
state: California
city: Norwich
country: United States
facility: Eastern CT Hematology and Oncology Associates
state: Connecticut
city: Clermont
country: United States
facility: Clermont Oncology Center
state: Florida
city: Miami
country: United States
facility: Miami Veterans Administration HealthCare System
state: Florida
city: Orange City
country: United States
facility: Mid Florida Hematology and Oncology Center
state: Florida
city: Saint Petersburg
country: United States
facility: Pinellas Hematology and Oncology
state: Florida
city: Tallahassee
country: United States
facility: Tallahassee Memorial Healthcare
state: Florida
city: Tampa
country: United States
facility: Moffitt Cancer Center
state: Florida
city: Chicago
country: United States
facility: University of Illinois
state: Illinois
city: Baton Rouge
country: United States
facility: Mary Bird Perkins Cancer Center
state: Louisiana
city: Hattiesburg
country: United States
facility: Hattiesburg Clinic
state: Mississippi
city: Saint Louis
country: United States
facility: Mercy South
state: Missouri
city: Pennington
country: United States
facility: Capital Health Hopewell Medical Center
state: New Jersey
city: Albuquerque
country: United States
facility: New Mexico Cancer Care Alliance
state: New Mexico
city: Port Jefferson Station
country: United States
facility: New York Cancer and Blood Specialists
state: New York
city: Westbury
country: United States
facility: Clinical Research Alliance Inc
state: New York
city: Canton
country: United States
facility: Gabrail Cancer Center Research
state: Ohio
city: Knoxville
country: United States
facility: Thompson Cancer Survival Center (TCSC ) - Downtown
state: Tennessee
city: Knoxville
country: United States
facility: University of Tennessee Medical Center
state: Tennessee
city: El Paso
country: United States
facility: Renovatio Clinical
state: Texas
city: Houston
country: United States
facility: MD Anderson Cancer Center
state: Texas
city: Charlottesville
country: United States
facility: University of Virginia Medical Center
state: Virginia
city: Midlothian
country: United States
facility: Bon Secours Cancer Institute Richmond
state: Virginia
city: Macquarie Park
country: Australia
facility: Macquarie University Health Science Center (MQ Health)
state: New South Wales
city: Wagga Wagga
country: Australia
facility: Riverina Cancer Care Centre (RCCC)
state: New South Wales
city: Wollongong
country: Australia
facility: Southern Medical Day Care Centre
state: New South Wales
city: Ballarat
country: Australia
facility: Ballarat Regional Integrated Cancer Centre (BRICC)
state: Victoria
city: Bendigo
country: Australia
facility: Bendigo Hospital
state: Victoria
city: Kelowna
country: Canada
facility: British Columbia Cancer Center-Kelowna
state: British Columbia
city: Batumi
country: Georgia
facility: Cancer Center of Adjara
state: Adjaria
city: Tbilisi
country: Georgia
facility: Israeli Georgian Medical Research Clinic Helsicore
city: Tbilisi
country: Georgia
facility: NNLE New Vision University Hospital
city: Tbilisi
country: Georgia
facility: The Institute of Clinical Oncology
city: Tbilisi
country: Georgia
facility: TIM - Tbilisi Institute of Medicine
city: Tbilisi
country: Georgia
facility: Research Institute of Clinical Medicine
city: Tbilisi
country: Georgia
facility: Tbilisi State Medical University and Ingorokva High Medical Technology University Clinic
city: Tbilisi
country: Georgia
facility: JSC Evex Hospitals - Caraps Medline
city: Beer-Sheba
country: Israel
facility: Soroka University Medical Center
state: HaDarom
city: Jerusalem
country: Israel
facility: Shaare Zedek Medical Center
city: Tel Aviv
country: Israel
facility: Tel Aviv Sourasky Medical Center
city: Tel Aviv
country: Israel
facility: Assuta Medical Centers
city: Cheongju-si
country: Korea, Republic of
facility: Chungbuk National University Hospital
state: Chungbuk
city: Suwon-si
country: Korea, Republic of
facility: St. Vincents Hospital - The Catholic University of Korea
state: Gyeonggi-do
city: Suwon-si
country: Korea, Republic of
facility: Ajou University Hospital
state: Gyeonggi-do
city: Jeonju
country: Korea, Republic of
facility: Jeonbuk National University Hospital
state: Jeollabuk-do
city: Daejeon
country: Korea, Republic of
facility: Chungnam National University Hospital
city: Incheon
country: Korea, Republic of
facility: Gachon University Gil Medical Center
city: Incheon
country: Korea, Republic of
facility: Inha University Hospital
city: Seoul
country: Korea, Republic of
facility: Korea University Guro Hospital
city: Ulsan
country: Korea, Republic of
facility: Ulsan University Hospital
city: Johor Bahru
country: Malaysia
facility: Hospital Sultan Ismail
state: Johor
city: Kuantan
country: Malaysia
facility: Hospital Tengku Ampuan Afzan( HTTA)
state: Pahang
city: Putrajaya
country: Malaysia
facility: National Cancer Institute
state: Wilayah Persekutuan Putrajaya
city: Kuala Lumpur
country: Malaysia
facility: Hospital Kuala Lumpur
state: Wilayah Persekutuan
city: Pulau Pinang
country: Malaysia
facility: Hospital Pulau Pinang
city: Santiago de Compostela
country: Spain
facility: Hospital Clinico Universitario Santiago de Compostela
state: A Coruna
city: Oviedo
country: Spain
facility: Hospital Universitario Central de Asturias
state: Asturias
city: Palma
country: Spain
facility: Son Espases
state: Balearic Islands
city: Barcelona
country: Spain
facility: Instituto Oncologico Dr Rosell Hospital Universitari Quiron Dexeus Location
state: Catalunya
city: Majadahonda
country: Spain
facility: Hospital Universitario Puerta de Hierro - Majadahonda
state: Madrid
city: Barcelona
country: Spain
facility: Vall d'Hebron Barcelona Hospital Campus
city: Madrid
country: Spain
facility: Hospital Clinico San Carlos
city: Malaga
country: Spain
facility: Hospital Regional Universitario de Malaga
city: Sevilla
country: Spain
facility: Hospital De Valme
city: Dalin
country: Taiwan
facility: Dalin Tzu Chi Hospital
state: Chia-yi County
city: Hualien City
country: Taiwan
facility: Buddhist Tzu Chi General Hospital
state: Hualien
city: Kaohsiung
country: Taiwan
facility: Chung-Ho Memorial Hospital
city: New Taipei City
country: Taiwan
facility: Taipei Medical University - Shuang Ho Hospital
city: Tainan
country: Taiwan
facility: National Cheng Kung University Hospital
city: Taipei City
country: Taiwan
facility: Tri-Service General Hospital
city: Taipei
country: Taiwan
facility: National Taiwan University Hospital
city: Taipei
country: Taiwan
facility: Taipei Medical University Hospital
city: Dusit
country: Thailand
facility: Navamindradhiraj University
state: Bangkok
city: Lampang
country: Thailand
facility: Lampang Cancer Center
state: Lampang Province
city: Hat-Yai
country: Thailand
facility: Prince Of Songkla Hospital, Prince Of Songkhla University
state: Songkhla
city: Bangkok
country: Thailand
facility: King Chulalongkorn Memorial Hospital
city: Bangkok
country: Thailand
facility: Siriraj Hospital
city: Chiang Mai
country: Thailand
facility: Chiang Mai University
city: Altindag
country: Turkey
facility: Hacettepe University Medical Faculty
state: Ankara
city: Istanbul
country: Turkey
facility: Medipol University Hospital
state: Bagcilar
city: Bursa
country: Turkey
facility: Bursa Uludag University Medical Faculty
state: Gorukle Bursa Turkiye
city: Pendik
country: Turkey
facility: Istinye University VMMedical Park Pendik Hospital
state: Istanbul
city: Kocaeli
country: Turkey
facility: Kocaeli University Hospital
state: Marmara
city: Konya
country: Turkey
facility: Necmettin Erbakan University Meram Faculty of Medicine
state: Meram
city: Kurupelit
country: Turkey
facility: Ondokuz Mayıs University
state: Samsun
city: Gaziantep
country: Turkey
facility: Gaziantep Medicalpoint Hospital
state: Sehitkamil
city: Sakarya
country: Turkey
facility: Sakarya University
state: Serdivan
city: Adana
country: Turkey
facility: Acibadem Adana Hastanesi
state: Seyhan
city: Adana
country: Turkey
facility: Adana City Education and Research Hospital
state: Yuregir
city: Adana
country: Turkey
facility: Baskent University
city: Ankara
country: Turkey
facility: Ankara Etlik Sehir Hastanesi Ankara Etlik City Hospital
city: Ankara
country: Turkey
facility: Gulhane Research And Training Hospital
city: Ankara
country: Turkey
facility: Ankara Yildirim Beyazit Universitesi - Tip Fakultesi
city: Ankara
country: Turkey
facility: Gazi University
city: Ankara
country: Turkey
facility: Liv Hospital Ankara
city: Ankara
country: Turkey
facility: Sbu Doctor Abdurrahman Yurtaslan Ankara Onkoloji Suam
city: Ankara
country: Turkey
facility: Yuksek Ihtisas Unıversity Medicalpark Hospital
city: Ankara
country: Turkey
facility: Memorial Ankara Hospital
city: Edirne
country: Turkey
facility: Trakya University
city: Istanbul
country: Turkey
facility: Koc University
city: Istanbul
country: Turkey
facility: Bezmialem Vakif University
city: Istanbul
country: Turkey
facility: Memorial Bahcelievler Hospital
city: Istanbul
country: Turkey
facility: Istanbul University Cerrahpasa at Cerrahpasa Medical Faculty
city: Istanbul
country: Turkey
facility: Istanbul Medeniyet University Prof.Dr.Suleyman Yalcin Şehir Hospital
city: Izmir
country: Turkey
facility: Izmir Dr.Suat Seren Gogus Hastaliklari Ve Cerrahisi Egitim Ve Arastirma Hastanesi
city: Izmir
country: Turkey
facility: Izmir Economy University Medical Point Hospital
city: Konya
country: Turkey
facility: Necmettin Erbakan University Meram Faculty of Medicine
city: Samsun
country: Turkey
facility: Vm Medicalpark Hospital
Study officials:
affiliation: Regeneron Pharmaceuticals
name: Clinical Trial Management
role: STUDY_DIRECTOR
References: