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)

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Regeneron Pharmaceuticals Inc.

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

28 Mar 2025 → ongoing

Decision date (initial)

2024-05-22

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

Regeneron Pharmaceuticals Inc.

External identifiers

EU CT number

2022-501483-18-00

ClinicalTrials.gov

NCT05785767

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Safety, Pharmacokinetic

Primary Objective: Phase 2
To assess the objective response rate (ORR) per blinded independent central review committee (BICR) of combination of cemiplimab and fianlimab at two doses compared with cemiplimab monotherapy in the first-line treatment of patients with advanced NSCLC whose tumors express PD-L1 in ≥50% of tumor cells.

Primary Objective: Phase 3:
To compare overall survival (OS) of the combination of cemiplimab and fianlimab versus cemiplimab monotherapy.

Secondary objectives 12

1. Phase 2: To assess the safety and tolerability of combination of cemiplimab and fianlimab compared to cemiplimab monotherapy.
2. Phase 2: To assess other anti-tumor activities of combination of cemiplimab and fianlimab compared to cemiplimab monotherapy, as assessed by ORR by investigator assessment, disease control rate (DCR), time to tumor response (TTR), duration of response (DOR), progression free survival (PFS) by BICR and investigator assessment, and OS.
3. Phase 2: To assess the patient-reported outcomes (via European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC-QLQ-C30), Quality of Life Questionnaire Lung Cancer 13 (LC13), and EuroQoL 5-Dimensional 5-Level Scale (EQ-5D- 5L)) of combination of cemiplimab and fianlimab compared with cemiplimab monotherapy.
4. Phase 2: To assess patient-reported fatigue as measured by the fatigue severity and interference with usual or daily activities items of the patient reported outcome (PRO) Common Terminology Criteria for Adverse Events (CTCAE) for combination of cemiplimab and fianlimab compared with cemiplimab monotherapy.
5. Phase 2: To characterize the pharmacokinetics (PK) of fianlimab and cemiplimab.
6. Phase 2: To assess the immunogenicity of fianlimab and cemiplimab.
7. Phase 3: To assess the safety and tolerability of combination of cemiplimab and fianlimab compared to cemiplimab monotherapy.
8. Phase 3: To assess other anti-tumor activities of combination of cemiplimab and fianlimab and cemiplimab monotherapy, as measured by ORR, DCR, TTR, DOR, and PFS, by BICR and investigator assessment.
9. Phase 3: To assess the patient-reported outcomes (via EORTC-QLQ-C30, -LC13, and EQ-5D- 5L) of combination of cemiplimab and fianlimab compared with cemiplimab monotherapy.
10. Phase 3: To assess patient-reported fatigue as measured by the fatigue severity and interference items of the PRO CTCAE for combination of cemiplimab and fianlimab compared with cemiplimab.
11. Phase 3: To characterize the PK of fianlimab and cemiplimab.
12. Phase 3: To assess the immunogenicity of fianlimab and cemiplimab

Conditions and MedDRA coding

Advanced Non-Small Cell Lung Cancer

Study design 4 periods

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 7

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 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
7. Additional protocol defined inclusion criteria apply

Exclusion criteria 10

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: 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
10. Additional protocol defined exclusion criteria apply

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 2

1. 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)
2. Overall survival (OS) (Phase 3)

Secondary endpoints 43

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

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Comparator 1

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Regeneron Pharmaceuticals Inc.

Sponsor organisation

Regeneron Pharmaceuticals Inc.

Address

777 Old Saw Mill River Road

City

Tarrytown

Postcode

10591-6717

Country

United States

Scientific contact point

Organisation

Regeneron Pharmaceuticals Inc.

Contact name

Clinical Trial Information

Public contact point

Organisation

Regeneron Pharmaceuticals Inc.

Contact name

Clinical Trial Information

Third parties 8

Locations

4 EU/EEA countries · 31 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 26 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

7 submissions — initial application plus substantial / non-substantial modifications