FIANLIMAB for Advanced non-small cell lung cancer

Inclusion criteria

• {"criterion_text":"- 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.\n- Availability of an archival or on-study formalin-fixed, paraffin-embedded tumor tissue sample, without intervening therapy between biopsy collection and screening as described in the protocol\n- 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.\n- 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\n- Eastern Cooperative Oncology Group (ECOG) performance status of ≤1\n- Adequate organ and bone marrow function\n- Additional protocol defined inclusion criteria apply"}

Exclusion criteria

• {"criterion_text":"- Patients who have never smoked, defined as smoking ≤100 cigarettes in a lifetime\n- 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\n- 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.\n- Encephalitis, meningitis, or uncontrolled seizures in the year prior to enrollment\n- 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.\n- 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)\n- 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\n- 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\n- Patients who have received prior systemic therapies are excluded with the exception of the following: a. 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. b. Anti-PD-L1 with or without LAG-3 as an adjuvant or neoadjuvant therapy as long as the last dose is >12 months prior to enrollment. c. Prior exposure to other immunomodulatory or vaccine therapies such as anti-CTLA-4 antibodies as long as the last dose is >3 months prior to enrollment. Immune-mediated AEs must be resolved to CTCAE grade ≤1 or baseline by the time of enrollment. Endocrine immunemediated AEs controlled with hormonal or other nonimmunosuppressive therapies without resolution prior to enrollment are allowed\n- Additional protocol defined exclusion criteria apply"}

Primary endpoints

• {"endpoint_text":"- 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) (Phase 2)","definition_or_measurement_approach":"Assessed by blinded independent central review (BICR) using RECIST v1.1 (Phase 2)"}
• {"endpoint_text":"- Overall survival (OS) (Phase 3)","definition_or_measurement_approach":"Overall survival (OS) comparison between treatment arms (Phase 3)"}

Secondary endpoints

• {"endpoint_text":"- Incidence of treatment-emergent adverse events (TEAEs) (Phase 2 and Phase 3)","definition_or_measurement_approach":"Incidence of TEAEs (Phase 2 and Phase 3)"}
• {"endpoint_text":"- Incidence of treatment-related TEAEs (Phase 2 and Phase 3)","definition_or_measurement_approach":"Incidence of treatment-related TEAEs (Phase 2 and Phase 3)"}
• {"endpoint_text":"- Incidence of serious adverse events (SAEs) (Phase 2 and Phase 3)","definition_or_measurement_approach":"Incidence of SAEs (Phase 2 and Phase 3)"}
• {"endpoint_text":"- Incidence of adverse events of special interest (AESIs) (Phase 2 and Phase 3)","definition_or_measurement_approach":"Incidence of AESIs (Phase 2 and Phase 3)"}
• {"endpoint_text":"- Incidence of immune-mediated adverse events (imAEs) (Phase 2 and Phase 3)","definition_or_measurement_approach":"Incidence of immune-mediated AEs (imAEs) (Phase 2 and Phase 3)"}
• {"endpoint_text":"- Occurrence of interruption of study drug(s) due to TEAEs (Phase 2 and Phase 3)","definition_or_measurement_approach":"Occurrence of study drug interruption due to TEAEs (Phase 2 and Phase 3)"}
• {"endpoint_text":"- Occurrence of discontinuation of study drug(s) due to TEAEs (Phase 2 and Phase 3)","definition_or_measurement_approach":"Occurrence of study drug discontinuation due to TEAEs (Phase 2 and Phase 3)"}
• {"endpoint_text":"- Occurrence of interruption of study drug(s) due to AESIs (Phase 2 and Phase 3)","definition_or_measurement_approach":"Occurrence of study drug interruption due to AESIs (Phase 2 and Phase 3)"}
• {"endpoint_text":"- Occurrence of discontinuation of study drug(s) due to AESIs (Phase 2 and Phase 3)","definition_or_measurement_approach":"Occurrence of study drug discontinuation due to AESIs (Phase 2 and Phase 3)"}
• {"endpoint_text":"- Occurrence of interruption of study drug(s) due to imAEs (Phase 2 and Phase 3)","definition_or_measurement_approach":"Occurrence of study drug interruption due to imAEs (Phase 2 and Phase 3)"}
• {"endpoint_text":"- Occurrence of discontinuation of study drug(s) due to imAEs (Phase 2 and Phase 3)","definition_or_measurement_approach":"Occurrence of study drug discontinuation due to imAEs (Phase 2 and Phase 3)"}
• {"endpoint_text":"- Incidence of deaths due to TEAE (Phase 2 and Phase 3)","definition_or_measurement_approach":"Incidence of deaths attributable to TEAEs (Phase 2 and Phase 3)"}
• {"endpoint_text":"- Incidence of grade 3 to 4 laboratory abnormalities (Phase 2 and Phase 3)","definition_or_measurement_approach":"Incidence of grade 3–4 laboratory abnormalities (Phase 2 and Phase 3)"}
• {"endpoint_text":"- ORR by investigator assessment, using RECIST 1.1 (Phase 2)","definition_or_measurement_approach":"ORR assessed by investigator per RECIST v1.1 (Phase 2)"}
• {"endpoint_text":"- Disease control rate (DCR) by BICR (Phase 2 and Phase 3)","definition_or_measurement_approach":"DCR assessed by blinded independent central review (BICR) (Phase 2 and Phase 3)"}
• {"endpoint_text":"- DCR by investigator assessment (Phase 2 and Phase 3)","definition_or_measurement_approach":"DCR by investigator assessment (Phase 2 and Phase 3)"}
• {"endpoint_text":"- Time to tumor response (TTR) by BICR (Phase 2 and Phase 3)","definition_or_measurement_approach":"TTR assessed by BICR (Phase 2 and Phase 3)"}
• {"endpoint_text":"- TTR by investigator assessment (Phase 2 and Phase 3)","definition_or_measurement_approach":"TTR by investigator assessment (Phase 2 and Phase 3)"}
• {"endpoint_text":"- Duration of response (DOR) by BICR (Phase 2 and Phase 3)","definition_or_measurement_approach":"DOR assessed by BICR (Phase 2 and Phase 3)"}
• {"endpoint_text":"- DOR by investigator assessment (Phase 2 and Phase 3)","definition_or_measurement_approach":"DOR by investigator assessment (Phase 2 and Phase 3)"}
• {"endpoint_text":"- Progression free survival (PFS) by BICR (Phase 2 and Phase 3)","definition_or_measurement_approach":"PFS assessed by BICR (Phase 2 and Phase 3)"}
• {"endpoint_text":"- PFS by investigator assessment (Phase 2 and Phase 3)","definition_or_measurement_approach":"PFS by investigator assessment (Phase 2 and Phase 3)"}
• {"endpoint_text":"- Overall survival (OS) (Phase 2)","definition_or_measurement_approach":"Overall survival (Phase 2)"}
• {"endpoint_text":"- Change from baseline in patient-reported Global health status/QoL per European Organization for Research and Treatment of Cancer Quality of Life Core Questionnaire (EORTC QLQ C30) (Phase 2 and Phase 3)","definition_or_measurement_approach":"Change from baseline in patient-reported global health status/QoL per EORTC QLQ-C30 (Phase 2 and Phase 3)"}
• {"endpoint_text":"- Change from baseline in patient-reported physical functioning per EORTC QLQ C30 (Phase 2 and Phase 3)","definition_or_measurement_approach":"Change from baseline in patient-reported physical functioning per EORTC QLQ-C30 (Phase 2 and Phase 3)"}
• {"endpoint_text":"- 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) (Phase 2 and Phase 3)","definition_or_measurement_approach":"Change from baseline in patient-reported chest pain per EORTC QLQ-LC13 (Phase 2 and Phase 3)"}
• {"endpoint_text":"- Change from baseline in patient-reported dyspnea per EORTC QLQ-LC13 (Phase 2 and Phase 3)","definition_or_measurement_approach":"Change from baseline in patient-reported dyspnea per EORTC QLQ-LC13 (Phase 2 and Phase 3)"}
• {"endpoint_text":"- Change from baseline in patient-reported cough per EORTC QLQ-LC13 (Phase 2 and Phase 3)","definition_or_measurement_approach":"Change from baseline in patient-reported cough per EORTC QLQ-LC13 (Phase 2 and Phase 3)"}
• {"endpoint_text":"- Time until definitive deterioration in patient-reported global health status/QoL per EORTC QLQ-C30 (Phase 2 and Phase 3)","definition_or_measurement_approach":"Time until definitive deterioration in patient-reported global health status/QoL per EORTC QLQ-C30 (Phase 2 and Phase 3)"}
• {"endpoint_text":"- Time until definitive deterioration in patient-reported physical functioning per EORTC QLQ-C30 (Phase 2 and Phase 3)","definition_or_measurement_approach":"Time until definitive deterioration in patient-reported physical functioning per EORTC QLQ-C30 (Phase 2 and Phase 3)"}
• {"endpoint_text":"- Time until definitive deterioration in patient-reported chest pain per EORTC QLQ-LC13 (Phase 2 and Phase 3)","definition_or_measurement_approach":"Time until definitive deterioration in patient-reported chest pain per EORTC QLQ-LC13 (Phase 2 and Phase 3)"}
• {"endpoint_text":"- Time until definitive deterioration in patient-reported dyspnea per EORTC QLQ-LC13 (Phase 2 and Phase 3)","definition_or_measurement_approach":"Time until definitive deterioration in patient-reported dyspnea per EORTC QLQ-LC13 (Phase 2 and Phase 3)"}
• {"endpoint_text":"- Time until definitive deterioration in patient-reported cough per EORTC QLQ-LC13 (Phase 2 and Phase 3)","definition_or_measurement_approach":"Time until definitive deterioration in patient-reported cough per EORTC QLQ-LC13 (Phase 2 and Phase 3)"}
• {"endpoint_text":"- Time until definitive deterioration in patient-reported composite of chest pain, dyspnea and cough per EORTC QLQ-LC13 (Phase 2 and Phase 3)","definition_or_measurement_approach":"Time until definitive deterioration in patient-reported composite of chest pain, dyspnea and cough per EORTC QLQ-LC13 (Phase 2 and Phase 3)"}
• {"endpoint_text":"- Change from baseline in patient-reported general health status per EuroQoL-5 Dimensions, 5-level Questionnaire-Visual Analogue Score (EQ-5D-5L VAS) (Phase 2 and Phase 3)","definition_or_measurement_approach":"Change from baseline in patient-reported general health status per EQ-5D-5L VAS (Phase 2 and Phase 3)"}
• {"endpoint_text":"- 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). (Phase 2 and Phase 3)","definition_or_measurement_approach":"Change from baseline in patient-reported fatigue severity per PRO-CTCAE (Phase 2 and Phase 3)"}
• {"endpoint_text":"- 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). (Phase 2 and Phase 3)","definition_or_measurement_approach":"Change from baseline in patient-reported interference due to fatigue per PRO-CTCAE (Phase 2 and Phase 3)"}
• {"endpoint_text":"- Concentrations of cemiplimab in serum (Phase 2 and Phase 3)","definition_or_measurement_approach":"Serum concentrations (PK) of cemiplimab (Phase 2 and Phase 3)"}
• {"endpoint_text":"- Concentrations of fianlimab in serum (Phase 2 and Phase 3)","definition_or_measurement_approach":"Serum concentrations (PK) of fianlimab (Phase 2 and Phase 3)"}
• {"endpoint_text":"- Immunogenicity, as measured by anti-drug antibodies (ADA) to fianlimab (Phase 2 and Phase 3)","definition_or_measurement_approach":"Immunogenicity measured by ADA to fianlimab (Phase 2 and Phase 3)"}
• {"endpoint_text":"- Immunogenicity, as measured by ADA to cemiplimab (Phase 2 and Phase 3)","definition_or_measurement_approach":"Immunogenicity measured by ADA to cemiplimab (Phase 2 and Phase 3)"}
• {"endpoint_text":"- Immunogenicity, as measured by neutralizing antibodies (NAb) to fianlimab (Phase 2 and Phase 3)","definition_or_measurement_approach":"Immunogenicity measured by neutralizing antibodies (NAb) to fianlimab (Phase 2 and Phase 3)"}
• {"endpoint_text":"- Immunogenicity, as measured by NAb to cemiplimab (Phase 2 and Phase 3)","definition_or_measurement_approach":"Immunogenicity measured by neutralizing antibodies (NAb) to cemiplimab (Phase 2 and Phase 3)"}

Methods

• Clariness GmbH: Subject recruitment (listed in trial third parties with duties 'Subject recruitment'; contact emma.vandenban@clariness.com) and local investigational site recruitment at participating hospital/clinic oncology services as listed in country site records. Recruitment arrangements documents (K1) and ICF procedure documents are included in the trial documents.

Spain

Earliest CTIS Part Ii Submission Date

29-04-2024

Latest Decision Or Authorization Date

24-04-2026

Processing Time Days

725

Number Of Sites

11

Number Of Participants

34

Romania

Earliest CTIS Part Ii Submission Date

05-07-2024

Latest Decision Or Authorization Date

28-04-2026

Processing Time Days

656

Number Of Sites

10

Number Of Participants

30

Greece

Earliest CTIS Part Ii Submission Date

05-07-2024

Latest Decision Or Authorization Date

22-04-2026

Processing Time Days

656

Number Of Sites

10

Number Of Participants

30

France

Earliest CTIS Part Ii Submission Date

29-04-2024

Latest Decision Or Authorization Date

21-04-2026

Processing Time Days

722

Number Of Sites

2

Number Of Participants

8

Primary sponsor

Full Name

Regeneron Pharmaceuticals Inc.

Organisation Type

Pharmaceutical company

Country Of Registered Address

United States

Contract research organisations

Name

Icon Clinical Research Limited

Responsibilities

IDMC, Site Training (other listed codes present but values not provided)

Name

Iqvia Biotech LLC

Name

Medidata Solutions Inc.

Responsibilities

Medical Imaging

Name

Bioclinica Inc.

Responsibilities

Imaging

Name

Signant Health Management Limited

Responsibilities

eCOA

Third parties

• {"country":"Germany","full_name":"Clariness GmbH","duties_or_roles":"Subject recruitment","organisation_type":"Non-Pharmaceutical company"}
• {"country":"United States","full_name":"Yprime LLC","duties_or_roles":"","organisation_type":"Non-Pharmaceutical company"}
• {"country":"United States","full_name":"Medidata Solutions Inc.","duties_or_roles":"Medical Imaging","organisation_type":"Non-Pharmaceutical company"}
• {"country":"United States","full_name":"Iqvia Biotech LLC","duties_or_roles":"","organisation_type":"Pharmaceutical company"}
• {"country":"Ireland","full_name":"Icon Clinical Research Limited","duties_or_roles":"IDMC, Site Training","organisation_type":"Pharmaceutical company"}
• {"country":"United Kingdom","full_name":"Signant Health Management Limited","duties_or_roles":"eCOA","organisation_type":"Non-Pharmaceutical company"}
• {"country":"United States","full_name":"Bioclinica Inc.","duties_or_roles":"Imaging","organisation_type":"Laboratory/Research/Testing facility"}
• {"country":"United States","full_name":"Ventana Medical Systems Inc.","duties_or_roles":"Specialty Laboratory","organisation_type":"Pharmaceutical company"}