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)

Advanced Non-Small Cell Lung Cancer Clinical Trial

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%

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05785767
• Other study ID #: R3767-ONC-2235
• Secondary ID: 2022-501483-18-0
• Status: Recruiting
• Phase: Phase 2/Phase 3
• Start date: June 30, 2023
• Est. completion date: February 5, 2032

Study information

• Verified date: May 2024
• Source: Regeneron Pharmaceuticals
• Contact: Clinical Trials Administrator
• Phone: 844-734-6643
• Email: clinicaltrials[@]regeneron.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 850
• Est. completion date: February 5, 2032
• Est. primary completion date: March 11, 2030
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Advanced Non-Small Cell Lung Cancer
• Carcinoma, Non-Small-Cell Lung
• Lung Neoplasms

Intervention

Drug:
• fianlimab
Every three weeks (Q3W) as intravenous (IV) co-infusion
• cemiplimab
Q3W as IV co-infusion
• Placebo
Q3W as IV co-infusion

Locations

Country	Name	City	State
Australia	Ballarat Regional Integrated Cancer Centre (BRICC)	Ballarat	Victoria
Australia	Bendigo Hospital	Bendigo	Victoria
Australia	Macquarie University Health Science Center (MQ Health)	Macquarie Park	New South Wales
Australia	Riverina Cancer Care Centre (RCCC)	Wagga Wagga	New South Wales
Australia	Southern Medical Day Care Centre	Wollongong	New South Wales
Canada	British Columbia Cancer Center- Kelowna	Kelowna	British Columbia
Georgia	LTD Cancer Center of Adjara	Batumi	Adjaria
Georgia	Israeli Georgian medical research clinic Helsicore	Tbilisi
Georgia	JSC Evex Hospitals- Caraps Medline	Tbilisi
Georgia	JSC K. Eristavi National Center of Experimental and Clinical Surgery	Tbilisi
Georgia	Research Institute of Clinical Medicine	Tbilisi
Georgia	Tbilisi State Medical University and Ingorokva High Medical Technology University Clinic	Tbilisi
Georgia	The Institute of Clinical Oncology	Tbilisi
Georgia	TIM - Tbilisi Institute of Medicine	Tbilisi
Israel	Shaare Zedek Medical Center	Jerusalem
Israel	Assuta Medical Centers	Tel Aviv
Israel	Tel Aviv Sourasky Medical Center	Tel Aviv
Korea, Republic of	Chungbuk National University Hospital	Cheongju-si	Chungbuk
Korea, Republic of	Chungnam National University Hospital	Daejeon
Korea, Republic of	Gachon University Gil Medical Center	Incheon
Korea, Republic of	Inha University Hospital	Incheon
Korea, Republic of	Jeonbuk National University Hospital	Jeonju	Jeollabuk-do
Korea, Republic of	Korea University Guro Hospital	Seoul
Korea, Republic of	Ajou University Hospital	Suwon	Gyeonggi
Korea, Republic of	Ulsan University Hospital	Ulsan
Malaysia	Hospital Sultan Ismail	Johor Bahru	Johor
Malaysia	Hospital Kuala Lumpur	Kuala Lumpur	WP
Malaysia	Hospital Tengku Ampuan Afzan (HTTA)	Kuantan	Pahang
Malaysia	Hospital Pulau Pinang	Pulau Pinang
Malaysia	National Cancer Institute	Putrajaya	Wilayah Persekutuan
Turkey	Gulhane Research and Training Hospital	Ankara
Turkey	Memorial Ankara Hospital	Ankara
United States	New Mexico Cancer Care Alliance/ University of New Mexico	Albuquerque	New Mexico
United States	Mary Bird Perkins Cancer Center	Baton Rouge	Louisiana
United States	Gabrail Cancer Center Research	Canton	Ohio
United States	University of Virginia Medical Center	Charlottesville	Virginia
United States	Clerrmont Oncology Center	Clermont	Florida
United States	Hattiesburg Clinic	Hattiesburg	Mississippi
United States	Thompson Cancer Survival Center (TCSC ) - Downtown	Knoxville	Tennessee
United States	University of Tennessee Medical Center	Knoxville	Tennessee
United States	Miami Veterans Administration HealthCare System	Miami	Florida
United States	Bon Secours Cancer Institute Richmond	Midlothian	Virginia
United States	Mid Florida Hematology and Oncology Center	Orange City	Florida
United States	Capital Health Medical Center	Pennington	New Jersey
United States	New York Cancer and Blood Specialists	Port Jefferson Station	New York
United States	Desert Hematology Oncology Medical Group, Inc.	Rancho Mirage	California
United States	Emad Ibrahim, MD, Inc.	Redlands	California
United States	Pinellas Hematology and Oncology	Saint Petersburg	Florida
United States	Clinical Research Alliance, Inc.	Westbury	New York
United States	Yuma Regional Medical Center	Yuma	Arizona

Sponsors (1)

Lead Sponsor	Collaborator
Regeneron Pharmaceuticals

Countries where clinical trial is conducted

United States,  Australia,  Canada,  Georgia,  Israel,  Korea, Republic of,  Malaysia,  Turkey, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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 Proportion of patients with a best overall response of confirmed complete response (CR) or partial response (PR)	Up to 136 weeks
Primary	Overall survival (OS)	Phase 3 The time from randomization to the date of death due to any cause	Up to 5 years
Secondary	Incidence of treatment-emergent adverse events (TEAEs)	Phase 2 and Phase 3 A TEAE is any untoward medical occurrence in a patient or clinical investigation participant administered a pharmaceutical product, which does not necessarily have a causal relationship with this treatment	Up to 136 weeks
Secondary	Incidence of treatment-related TEAEs	Phase 2 and Phase 3	Up to 136 weeks
Secondary	Incidence of serious adverse events (SAEs)	Phase 2 and Phase 3; Any untoward medical occurrence that at any dose: Results in death - includes all deaths, even those that appear to be completely unrelated to study drug (eg, a car accident in which a patient is a passenger); Is life-threatening; Requires in-patient hospitalization or prolongation of existing hospitalization • Results in persistent or significant disability/incapacity; Is a congenital anomaly/birth defect; Is an important medical event	Up to 136 weeks
Secondary	Incidence of adverse events of special interest (AESIs)	Phase 2 and Phase 3 Serious or non-serious; is one of scientific and medical concern specific to the sponsor's product or program, for which ongoing monitoring and rapid communication by the Investigator to the sponsor can be appropriate. Such an event might warrant further investigation in order to characterize and understand it.	Up to 136 weeks
Secondary	Incidence of immune-mediated adverse events (imAEs)	Phase 2 and Phase 3 Immune-mediated AEs are thought to be caused by unrestrained cellular immune responses directed at normal host tissues. An imAE can occur shortly after the first dose or several months after the last dose of treatment. Early detection and management reduces the risk of severe drug induced toxicity	Up to 136 weeks
Secondary	Occurrence of interruption of study drug(s) due to TEAEs	Phase 2 and Phase 3	Up to 136 weeks
Secondary	Occurrence of discontinuation of study drug(s) due to TEAEs	Phase 2 and Phase 3	Up to 136 weeks
Secondary	Occurrence of interruption of study drug(s) due to AESIs	Phase 2 and Phase 3	Up to 136 weeks
Secondary	Occurrence of discontinuation of study drug(s) due to AESIs	Phase 2 and Phase 3	Up to 136 weeks
Secondary	Occurrence of interruption of study drug(s) due to imAEs	Phase 2 and Phase 3	Up to 136 weeks
Secondary	Occurrence of discontinuation of study drug(s) due to imAEs	Phase 2 and Phase 3 A unique set of toxicities thought to be caused by unrestrained cellular immune responses	Up to 136 weeks
Secondary	Incidence of deaths due to TEAE	Phase 2 and Phase 3	Up to 136 weeks
Secondary	Incidence of grade 3 to 4 laboratory abnormalities	Phase 2 and Phase 3; = grade 3 per National Cancer Institute-Common Terminology Criteria for Adverse Events [NCI-CTCAE v5.0]	Up to 136 weeks
Secondary	ORR by investigator assessment, using RECIST 1.1	Phase 2	Up to 136 weeks
Secondary	Disease control rate (DCR) by BICR	Phase 2 and Phase 3 The proportion of patients with best overall response of complete response (CR), partial response (PR), or stable disease (SD)	Up to 136 weeks
Secondary	DCR by investigator assessment	Phase 2 and Phase 3	Up to 136 weeks
Secondary	Time to tumor response (TTR) by BICR	Phase 2 and Phase 3 The time from randomization to the date of the first response of CR or PR (whichever is first recorded) for patients with confirmed CR or PR.	Up to 136 weeks
Secondary	TTR by investigator assessment	Phase 2 and Phase 3	Up to 136 weeks
Secondary	Duration of response (DOR) by BICR	Phase 2 and Phase 3 The time from first response of CR or PR to first radiographic progression or death due to any cause for patients with confirmed CR or PR.	Up to 5 years
Secondary	DOR by investigator assessment	Phase 2 and Phase 3	Up to 5 years
Secondary	Progression free survival (PFS) by BICR	Phase 2 and Phase 3	Up to 5 years
Secondary	PFS by investigator assessment	Phase 2 and Phase 3	Up to 5 years
Secondary	Overall survival (OS)	Phase 2 The time from randomization to the date of death due to any cause	Up to 5 years
Secondary	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)	Phase 2 and Phase 3 EORTC-QLQ-C30 is a 30-item subject self-report questionnaire composed of both multi-item and single scales, including a GHS/QoL scale. Participants rate items on a four-point scale, with 1 as "not at all" and 4 as "very much." A change of 5 - 10 points is considered a small change. A change of 10 - 20 points is considered a moderate change.	Up to 5 years
Secondary	Change from baseline in patient-reported physical functioning per EORTC QLQ-C30	Phase 2 and Phase 3	Up to 5 years
Secondary	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 EORTC QLQ-LC 13 is a lung cancer specific module developed to assess lung cancer-associated symptoms and treatment-related side effects among lung cancer patients	Up to 5 years
Secondary	Change from baseline in patient-reported dyspnea per EORTC QLQ-LC13	Phase 2 and Phase 3	Up to 5 years
Secondary	Change from baseline in patient-reported cough per EORTC QLQ-LC13	Phase 2 and Phase 3	Up to 5 years
Secondary	Time until definitive deterioration in patient-reported global health status/QoL per EORTC QLQ-C30	Phase 2 and Phase 3	Up to 5 years
Secondary	Time until definitive deterioration in patient-reported physical functioning per EORTC QLQ-C30	Phase 2 and Phase 3	Up to 5 years
Secondary	Time until definitive deterioration in patient-reported chest pain per EORTC QLQ-LC13	Phase 2 and Phase 3	Up to 5 years
Secondary	Time until definitive deterioration in patient-reported dyspnea per EORTC QLQ-LC13	Phase 2 and Phase 3	Up to 5 years
Secondary	Time until definitive deterioration in patient-reported cough per EORTC QLQ-LC13	Phase 2 and Phase 3	Up to 5 years
Secondary	Time until definitive deterioration in patient-reported composite of chest pain, dyspnea and cough per EORTC QLQ-LC13	Phase 2 and Phase 3	Up to 5 years
Secondary	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 The EQ-5D-5L VAS records the respondent's self-rated health on a 10 centimeter (cm) vertical, visual analogue scale. It is rated by the respondent on a scale 0 to 100, with 0 being "the worst health you can imagine" and 100 being "the best health you can imagine".	Up to 5 years
Secondary	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 PRO-CTCAE questionnaire assesses side effect symptoms in cancer clinical trials using a PRO-CTCAE score. The PRO-CTCAE includes an item library of 124 items representing 78 symptomatic toxicities drawn from the CTCAE.	Up to 5 years
Secondary	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	Up to 5 years
Secondary	Concentrations of cemiplimab in serum	Phase 2 and Phase 3	Up to 136 weeks
Secondary	Concentrations of fianlimab in serum	Phase 2 and Phase 3	Up to 136 weeks
Secondary	Immunogenicity, as measured by anti-drug antibodies (ADA) to fianlimab	Phase 2 and Phase 3	Up to 136 weeks
Secondary	Immunogenicity, as measured by ADA to cemiplimab	Phase 2 and Phase 3	Up to 136 weeks
Secondary	Immunogenicity, as measured by neutralizing antibodies (NAb) to fianlimab	Phase 2 and Phase 3	Up to 136 weeks
Secondary	Immunogenicity, as measured by NAb to cemiplimab	Phase 2 and Phase 3	Up to 136 weeks