Clinical trial NCT05800015: A Trial to Learn How the Combination of Fianlimab With Cemiplimab and Chemotherapy Works Compared With Cemiplimab and Chemotherapy for Treating Adult Patients With Advanced Non-small Cell Lung Cancer
Official title: A Randomized, Double-Blind Phase 2/3 Study of Fianlimab (Anti-LAG-3 Antibody), Cemiplimab (Anti-PD-1 Antibody), and Chemotherapy Versus Cemiplimab and Chemotherapy in First-Line Treatment of Patients With Advanced Non-Small Cell Lung Cancer (NSCLC) Irrespective of PD-L1 Expression Levels
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
PHASE3
Conditions: Non-small Cell Lung Cancer
Keywords: NSCLC
Lung cancer
Programmed cell death ligand-1
PD-L1
Lymphocyte-activation gene 3
LAG-3
African descent
Lead sponsor: Regeneron Pharmaceuticals
Sponsor class: INDUSTRY
First posted: 2023-04-05
Enrollment: 950
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 fianlimab (also called REGN3767) with two other medications called cemiplimab and chemotherapy, individually called a "study drug" or collectively called "study drugs". 'Investigational' means that the study drug is not approved for use outside of this study by any Health Authority. Examples of chemotherapy drugs include the following: Paclitaxel plus carboplatin, and Pemetrexed plus cisplatin. The study is being conducted in patients who have advanced non-small cell lung cancer (NSCLC).

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

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

* What side effects may happen from taking the study drugs
* How much of each 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, expression results (regardless of expression level) 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 a valid PD-L1 result, regardless of expression level, using an assay as 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 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 defined in the protocol.

Key Exclusion Criteria:

1. 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.
2. Patients with tumors tested positive for actionable epidermal growth factor receptor (EGFR) gene mutations, anaplastic lymphoma kinase (ALK) gene translocations, or ROS oncogene 1 (ROS1) fusions, as described in the protocol.
3. Encephalitis, meningitis, or uncontrolled seizures in the year prior to enrollment.
4. 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.
5. 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).
6. 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.
7. 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.
8. 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 as an adjuvant or neoadjuvant therapy such as 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 review committee (BICR) using 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 event (TEAEs)
timeFrame: Up to 108 weeks
measure: Incidence of treatment-related TEAEs
timeFrame: Up to 108 weeks
measure: Incidence of serious adverse events (SAEs)
timeFrame: Up to 108 weeks
measure: Incidence of adverse events of special interest (AESIs)
timeFrame: Up to 108 weeks
measure: Incidence of immune-mediated adverse events (imAEs)
timeFrame: Up to 108 weeks
measure: Occurrence of interruption of study drug(s) due to AEs
timeFrame: Up to 108 weeks
measure: Occurrence of discontinuation of study drug(s) due to AEs
timeFrame: Up to 108 weeks
measure: Incidence of deaths due to TEAE
timeFrame: Up to 108 weeks
measure: Incidence of grade 3-4 laboratory abnormalities
timeFrame: Up to 108 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: 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 Questionnaire Core 30 (EORTC QLQ-C30)
timeFrame: Up to 108 weeks
measure: Change from baseline in physical functioning per EORTC QLQ-C30
timeFrame: Up to 108 weeks
measure: Change from baseline in patient-reported chest pain per European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Lung Cancer 13 (EORTC QLQ-LC13)
timeFrame: Up to 108 weeks
measure: Change from baseline in patient-reported dyspnea per EORTC QLQ-LC13
timeFrame: Up to 108 weeks
measure: Change from baseline in patient-reported cough per EORTC QLQ-LC13
timeFrame: Up to 108 weeks
measure: Time until definitive deterioration in patient-reported global health status/QoL per EORTC QLQ-C30
timeFrame: Up to 108 weeks
measure: Time until definitive deterioration in patient-reported physical functioning per EORTC QLQ-C30
timeFrame: Up to 108 weeks
measure: Time until definitive deterioration in patient-reported chest pain per EORTC QLQ-LC13
timeFrame: Up to 108 weeks
measure: Time until definitive deterioration in patient-reported dyspnea per EORTC QLQ-LC13
timeFrame: Up to 108 weeks
measure: Time until definitive deterioration in patient-reported cough per EORTC QLQ-LC13
timeFrame: Up to 108 weeks
measure: Time until definitive deterioration in a composite of these three symptoms: patient-reported chest pain, dyspnea and cough per EORTC QLQ-LC13
timeFrame: Up to 108 weeks
measure: Change from baseline in patient-reported general health status per EuroQoL 5-Dimensional 5-Level Scale (EQ-5D-5L) VAS
timeFrame: Up to 108 weeks
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 108 weeks
measure: Change from baseline in patient-reported interference with usual or daily activities due to fatigue per the PRO-CTCAE
timeFrame: Up to 108 weeks
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: Cerritos
country: United States
facility: The Oncology Institute of Hope & Innovation
state: California
city: Fullerton
country: United States
facility: Crosson Cancer Institute
state: California
city: Orange
country: United States
facility: St. Joseph Hospital Orange
state: California
city: Rancho Mirage
country: United States
facility: Desert Hematology Oncology Medical Group, Inc.
state: California
city: Redlands
country: United States
facility: Emad Ibrahim MD Inc.
state: California
city: Whittier
country: United States
facility: PIH Health Hospital
state: California
city: Aurora
country: United States
facility: Rocky Mountain Regional VA Medical Center
state: Colorado
city: New Haven
country: United States
facility: Yale Cancer Center
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: Tallahassee
country: United States
facility: Tallahassee Memorial Healthcare
state: Florida
city: Chicago
country: United States
facility: University of Illinois
state: Illinois
city: Rolling Meadows
country: United States
facility: Northwest Oncology and Hematology
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: 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: Bronx
country: United States
facility: Montefiore Medical Center
state: New York
city: New York
country: United States
facility: NYU Langone Health Perlmutter Cancer Center
state: New York
city: New York
country: United States
facility: Icahn School of Medicine at Mount Sinai
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: Germantown
country: United States
facility: West Cancer Center
state: Tennessee
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: 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: 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: Fitzroy
country: Australia
facility: St Vincents Hospital
state: Victoria
city: Murdoch
country: Australia
facility: St John of God Murdoch Hospital
state: Western Australia
city: Kelowna
country: Canada
facility: British Columbia Cancer Center-Kelowna
state: British Columbia
city: Laval
country: Canada
facility: Hopital Cite de la Sante
state: Quebec
city: Batumi
country: Georgia
facility: LLC High-Tech Hospital Medcenter
state: Adjaria
city: Tbilisi
country: Georgia
facility: Israeli Georgian Medical Research Clinic Helsicore
city: Tbilisi
country: Georgia
facility: LTD New Hospitals
city: Tbilisi
country: Georgia
facility: High Technology Medical Center, University Clinic Tbilisi
city: Tbilisi
country: Georgia
facility: LTD Archangel St. Michael Multiprofile Clinical Hospital
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: JSC Evex Hospitals - Caraps Medline
city: Ramat Gan
country: Israel
facility: Sheba Medical Center
state: Hamerkaz
city: Tel Aviv
country: Israel
facility: Assuta Medical Centers
city: Cheongju-si
country: Korea, Republic of
facility: Chungbuk National University Hospital
state: Chungbuk
city: Incheon
country: Korea, Republic of
facility: Gachon University Gil Medical Center
state: Gyeonggi Do
city: Seongnam-si
country: Korea, Republic of
facility: CHA Bundang Medical Center CHA University
state: Gyeonggi Do
city: Suwon-si
country: Korea, Republic of
facility: St. Vincent's 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: Seoul
country: Korea, Republic of
facility: Asan Medical Center
state: Seoul Teugbyeolsi
city: Daejeon
country: Korea, Republic of
facility: Chungnam National University Hospital
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: Tanjung Bungah
country: Malaysia
facility: Mount Miriam Cancer Hospital
state: Penang
city: Kuching
country: Malaysia
facility: Sarawak General Hospital
state: Sarawak
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: 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 City
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: Lampang
country: Thailand
facility: Lampang Cancer Center
state: Lampang Province
Study officials:
affiliation: Regeneron Pharmaceuticals
name: Clinical Trial Management
role: STUDY_DIRECTOR
References: