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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT05785767




Registration number
NCT05785767
Ethics application status
Date submitted
14/03/2023
Date registered
27/03/2023

Titles & IDs
Public title
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)
Scientific 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%
Secondary ID [1] 0 0
2022-501483-18-00
Secondary ID [2] 0 0
R3767-ONC-2235
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Advanced Non-Small Cell Lung Cancer 0 0
Condition category
Condition code
Cancer 0 0 0 0
Lung - Mesothelioma
Cancer 0 0 0 0
Lung - Non small cell
Cancer 0 0 0 0
Lung - Small cell

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - fianlimab
Treatment: Drugs - cemiplimab
Treatment: Drugs - Placebo

Experimental: A: fianlimab+cemiplimab - Phase 2: fianlimab (HD) Phase 3: fianlimab (chosen dose)

Experimental: B: fianlimab+cemiplimab - Phase 2: fianlimab (LD) Phase 3: fianlimab (chosen dose)

Experimental: C: cemiplimab monotherapy+placebo - Phase 2 and Phase 3


Treatment: Drugs: fianlimab
Every three weeks (Q3W) as intravenous (IV) co-infusion

Treatment: Drugs: cemiplimab
Q3W as IV co-infusion

Treatment: Drugs: Placebo
Q3W as IV co-infusion

Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
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)
Timepoint [1] 0 0
Up to 136 weeks
Primary outcome [2] 0 0
Overall survival (OS)
Timepoint [2] 0 0
Up to 5 years
Secondary outcome [1] 0 0
Incidence of treatment-emergent adverse events (TEAEs)
Timepoint [1] 0 0
Up to 136 weeks
Secondary outcome [2] 0 0
Incidence of treatment-related TEAEs
Timepoint [2] 0 0
Up to 136 weeks
Secondary outcome [3] 0 0
Incidence of serious adverse events (SAEs)
Timepoint [3] 0 0
Up to 136 weeks
Secondary outcome [4] 0 0
Incidence of adverse events of special interest (AESIs)
Timepoint [4] 0 0
Up to 136 weeks
Secondary outcome [5] 0 0
Incidence of immune-mediated adverse events (imAEs)
Timepoint [5] 0 0
Up to 136 weeks
Secondary outcome [6] 0 0
Occurrence of interruption of study drug(s) due to TEAEs
Timepoint [6] 0 0
Up to 136 weeks
Secondary outcome [7] 0 0
Occurrence of discontinuation of study drug(s) due to TEAEs
Timepoint [7] 0 0
Up to 136 weeks
Secondary outcome [8] 0 0
Occurrence of interruption of study drug(s) due to AESIs
Timepoint [8] 0 0
Up to 136 weeks
Secondary outcome [9] 0 0
Occurrence of discontinuation of study drug(s) due to AESIs
Timepoint [9] 0 0
Up to 136 weeks
Secondary outcome [10] 0 0
Occurrence of interruption of study drug(s) due to imAEs
Timepoint [10] 0 0
Up to 136 weeks
Secondary outcome [11] 0 0
Occurrence of discontinuation of study drug(s) due to imAEs
Timepoint [11] 0 0
Up to 136 weeks
Secondary outcome [12] 0 0
Incidence of deaths due to TEAE
Timepoint [12] 0 0
Up to 136 weeks
Secondary outcome [13] 0 0
Incidence of grade 3 to 4 laboratory abnormalities
Timepoint [13] 0 0
Up to 136 weeks
Secondary outcome [14] 0 0
ORR by investigator assessment, using RECIST 1.1
Timepoint [14] 0 0
Up to 136 weeks
Secondary outcome [15] 0 0
Disease control rate (DCR) by BICR
Timepoint [15] 0 0
Up to 136 weeks
Secondary outcome [16] 0 0
DCR by investigator assessment
Timepoint [16] 0 0
Up to 136 weeks
Secondary outcome [17] 0 0
Time to tumor response (TTR) by BICR
Timepoint [17] 0 0
Up to 136 weeks
Secondary outcome [18] 0 0
TTR by investigator assessment
Timepoint [18] 0 0
Up to 136 weeks
Secondary outcome [19] 0 0
Duration of response (DOR) by BICR
Timepoint [19] 0 0
Up to 5 years
Secondary outcome [20] 0 0
DOR by investigator assessment
Timepoint [20] 0 0
Up to 5 years
Secondary outcome [21] 0 0
Progression free survival (PFS) by BICR
Timepoint [21] 0 0
Up to 5 years
Secondary outcome [22] 0 0
PFS by investigator assessment
Timepoint [22] 0 0
Up to 5 years
Secondary outcome [23] 0 0
Overall survival (OS)
Timepoint [23] 0 0
Up to 5 years
Secondary outcome [24] 0 0
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)
Timepoint [24] 0 0
Up to 5 years
Secondary outcome [25] 0 0
Change from baseline in patient-reported physical functioning per EORTC QLQ-C30
Timepoint [25] 0 0
Up to 5 years
Secondary outcome [26] 0 0
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)
Timepoint [26] 0 0
Up to 5 years
Secondary outcome [27] 0 0
Change from baseline in patient-reported dyspnea per EORTC QLQ-LC13
Timepoint [27] 0 0
Up to 5 years
Secondary outcome [28] 0 0
Change from baseline in patient-reported cough per EORTC QLQ-LC13
Timepoint [28] 0 0
Up to 5 years
Secondary outcome [29] 0 0
Time until definitive deterioration in patient-reported global health status/QoL per EORTC QLQ-C30
Timepoint [29] 0 0
Up to 5 years
Secondary outcome [30] 0 0
Time until definitive deterioration in patient-reported physical functioning per EORTC QLQ-C30
Timepoint [30] 0 0
Up to 5 years
Secondary outcome [31] 0 0
Time until definitive deterioration in patient-reported chest pain per EORTC QLQ-LC13
Timepoint [31] 0 0
Up to 5 years
Secondary outcome [32] 0 0
Time until definitive deterioration in patient-reported dyspnea per EORTC QLQ-LC13
Timepoint [32] 0 0
Up to 5 years
Secondary outcome [33] 0 0
Time until definitive deterioration in patient-reported cough per EORTC QLQ-LC13
Timepoint [33] 0 0
Up to 5 years
Secondary outcome [34] 0 0
Time until definitive deterioration in patient-reported composite of chest pain, dyspnea and cough per EORTC QLQ-LC13
Timepoint [34] 0 0
Up to 5 years
Secondary outcome [35] 0 0
Change from baseline in patient-reported general health status per EuroQoL-5 Dimensions, 5-level Questionnaire-Visual Analogue Score (EQ-5D-5L VAS)
Timepoint [35] 0 0
Up to 5 years
Secondary outcome [36] 0 0
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).
Timepoint [36] 0 0
Up to 5 years
Secondary outcome [37] 0 0
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).
Timepoint [37] 0 0
Up to 5 years
Secondary outcome [38] 0 0
Concentrations of cemiplimab in serum
Timepoint [38] 0 0
Up to 136 weeks
Secondary outcome [39] 0 0
Concentrations of fianlimab in serum
Timepoint [39] 0 0
Up to 136 weeks
Secondary outcome [40] 0 0
Immunogenicity, as measured by anti-drug antibodies (ADA) to fianlimab
Timepoint [40] 0 0
Up to 136 weeks
Secondary outcome [41] 0 0
Immunogenicity, as measured by ADA to cemiplimab
Timepoint [41] 0 0
Up to 136 weeks
Secondary outcome [42] 0 0
Immunogenicity, as measured by neutralizing antibodies (NAb) to fianlimab
Timepoint [42] 0 0
Up to 136 weeks
Secondary outcome [43] 0 0
Immunogenicity, as measured by NAb to cemiplimab
Timepoint [43] 0 0
Up to 136 weeks

Eligibility
Key inclusion criteria
Key

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
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
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.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 2
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,VIC
Recruitment hospital [1] 0 0
Macquarie University Health Science Center (MQ Health) - Macquarie Park
Recruitment hospital [2] 0 0
Riverina Cancer Care Centre (RCCC) - Wagga Wagga
Recruitment hospital [3] 0 0
Southern Medical Day Care Centre - Wollongong
Recruitment hospital [4] 0 0
Ballarat Regional Integrated Cancer Centre (BRICC) - Ballarat
Recruitment hospital [5] 0 0
Bendigo Hospital - Bendigo
Recruitment postcode(s) [1] 0 0
2109 - Macquarie Park
Recruitment postcode(s) [2] 0 0
2650 - Wagga Wagga
Recruitment postcode(s) [3] 0 0
NSW 2500 - Wollongong
Recruitment postcode(s) [4] 0 0
3350 - Ballarat
Recruitment postcode(s) [5] 0 0
3550 - Bendigo
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Arizona
Country [2] 0 0
United States of America
State/province [2] 0 0
California
Country [3] 0 0
United States of America
State/province [3] 0 0
Florida
Country [4] 0 0
United States of America
State/province [4] 0 0
Louisiana
Country [5] 0 0
United States of America
State/province [5] 0 0
Mississippi
Country [6] 0 0
United States of America
State/province [6] 0 0
New Jersey
Country [7] 0 0
United States of America
State/province [7] 0 0
New Mexico
Country [8] 0 0
United States of America
State/province [8] 0 0
New York
Country [9] 0 0
United States of America
State/province [9] 0 0
Ohio
Country [10] 0 0
United States of America
State/province [10] 0 0
Tennessee
Country [11] 0 0
United States of America
State/province [11] 0 0
Virginia
Country [12] 0 0
Canada
State/province [12] 0 0
British Columbia
Country [13] 0 0
Georgia
State/province [13] 0 0
Adjaria
Country [14] 0 0
Georgia
State/province [14] 0 0
Tbilisi
Country [15] 0 0
Israel
State/province [15] 0 0
HaDarom
Country [16] 0 0
Israel
State/province [16] 0 0
Jerusalem
Country [17] 0 0
Israel
State/province [17] 0 0
Tel Aviv
Country [18] 0 0
Korea, Republic of
State/province [18] 0 0
Chungbuk
Country [19] 0 0
Korea, Republic of
State/province [19] 0 0
Gyeonggi
Country [20] 0 0
Korea, Republic of
State/province [20] 0 0
Jeollabuk-do
Country [21] 0 0
Korea, Republic of
State/province [21] 0 0
Daejeon
Country [22] 0 0
Korea, Republic of
State/province [22] 0 0
Incheon
Country [23] 0 0
Korea, Republic of
State/province [23] 0 0
Seoul
Country [24] 0 0
Korea, Republic of
State/province [24] 0 0
Suwon
Country [25] 0 0
Korea, Republic of
State/province [25] 0 0
Ulsan
Country [26] 0 0
Malaysia
State/province [26] 0 0
Johor
Country [27] 0 0
Malaysia
State/province [27] 0 0
Pahang
Country [28] 0 0
Malaysia
State/province [28] 0 0
Wilayah Persekutuan
Country [29] 0 0
Malaysia
State/province [29] 0 0
WP
Country [30] 0 0
Malaysia
State/province [30] 0 0
Pulau Pinang
Country [31] 0 0
Taiwan
State/province [31] 0 0
Hualien City
Country [32] 0 0
Taiwan
State/province [32] 0 0
Kaohsiung
Country [33] 0 0
Taiwan
State/province [33] 0 0
New Taipei City
Country [34] 0 0
Taiwan
State/province [34] 0 0
Taipei
Country [35] 0 0
Thailand
State/province [35] 0 0
Lampang
Country [36] 0 0
Turkey
State/province [36] 0 0
Meram
Country [37] 0 0
Turkey
State/province [37] 0 0
Samsun
Country [38] 0 0
Turkey
State/province [38] 0 0
Ankara

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Regeneron Pharmaceuticals
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Clinical Trial Management
Address 0 0
Regeneron Pharmaceuticals
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Clinical Trials Administrator
Address 0 0
Country 0 0
Phone 0 0
844-734-6643
Fax 0 0
Email 0 0
Contact person for scientific queries

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
What data in particular will be shared?
All Individual Patient Data (IPD) that underlie publicly available results will be considered for sharing

Supporting document/s available: Study protocol, Statistical analysis plan (SAP), Informed consent form (ICF), Clinical study report (CSR), Analytic code
When will data be available (start and end dates)?
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 made the study results publicly available (e.g., scientific publication, scientific conference, clinical trial registry), has the legal authority to share the data, and has ensured the ability to protect participant privacy.
Available to whom?
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
Available for what types of analyses?
How or where can data be obtained?
IPD available at link: https://vivli.org/


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

No documents have been uploaded by study researchers.