A Trial to Learn if the Combination of Fianlimab, Cemiplimab, and Chemotherapy is Safe and Works Better Than the Combination of Cemiplimab and Chemotherapy in Adult Patients With Non-small Cell Lung Cancer That Can be Treated With Surgery.

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

24 Apr 2025 → ongoing

Decision date (initial)

2024-11-07

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

External identifiers

EU CT number

2023-505172-29-00

ClinicalTrials.gov

NCT06161441

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Pharmacokinetic, Efficacy, Safety

To assess pathological complete response (pCR) by blinded independent pathological review (BIPR) of fianlimab plus cemiplimab plus chemotherapy and cemiplimab plus chemotherapy in patients with resectable stage II to IIIB (N2) NSCLC.

Secondary objectives 6

1. To assess the efficacy of fianlimab plus cemiplimab plus chemotherapy and cemiplimab plus chemotherapy in patients with resectable stage II to IIIB (N2) NSCLC as measured by: EFS by investigator assessment − MPR by BIPR − Tumor response by investigator assessment − Pathologic response by local pathology review (pCR, MPR)
2. To assess safety and tolerability of each treatment arm
3. To characterize pharmacokinetics (PK) of fianlimab and cemiplimab
4. To assess immunogenicity of fianlimab and cemiplimab
5. To assess the feasibility of surgery and rate of peri-operative complications related to surgery (within 90 days of surgery)
6. To assess impact of fianlimab plus cemiplimab plus chemotherapy and cemiplimab plus chemotherapy on patient-reported outcomes, including HRQoL, functioning, lung cancer symptoms and general health status

Conditions and MedDRA coding

Resectable Non-small Cell Lung Cancer

Study design 2 periods

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 7

1. Patients with newly diagnosed, histologically confirmed, fully resectable stage II to IIIB (N2) NSCLC as per American Joint Committee on Cancer (AJCC) version 8
2. For patients with evidence of mediastinal adenopathy on imaging, mediastinal lymph node sampling is required as defined in the protocol
3. All patients must have disease status showing no evidence of distant metastases documented by a complete physical examination and imaging studies performed within 4 weeks prior to randomization as defined in the protocol
4. A patient must have an evaluable Programmed cell death ligand-1 (PD-L1) immunohistochemistry (IHC) result as defined in the protocol
5. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
6. Adequate bone marrow, hepatic and kidney function as defined in the protocol
7. Other protocol-defined Inclusion Criteria apply

Exclusion criteria 6

1. Any evidence of locally advanced unresectable or metastatic disease as defined in the protocol
2. Patients with tumors with known Epidermal growth factor receptor (EGFR) gene mutations, anaplastic lymphoma kinase (ALK) gene translocations as defined in the protocol
3. Uncontrolled infection with human immunodeficiency virus (HIV), hepatitis B (HBV) or hepatitis C virus (HCV) infection as defined in the protocol
4. Treatment with anti-cancer therapy including immunotherapy, chemotherapy, radiotherapy, or biological therapy in the 3 years prior to randomization. Adjuvant hormonotherapy used for breast cancer or other hormone-sensitive cancers in long term remission is allowed.
5. Patients with a history of myocarditis
6. Other protocol-defined Exclusion Criteria apply

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Pathological complete response (pCR) as evaluated by blinded independent pathological review (BIPR) in post-treatment resected tumor samples

Secondary endpoints 44

1. Event-Free Survival (EFS)
2. Major pathological response (MPR) by BIPR in post-treatment resected tumor samples
3. MPR by local pathology review in post-treatment resected tumor samples
4. Tumor response to neoadjuvant therapy per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1) criteria by investigator assessment
5. Occurrence of Adverse events (AEs)
6. Occurrence of Treatment-emergent adverse event (TEAEs)
7. Occurrence of Serious adverse events (SAEs)
8. Occurrence of Adverse events of special interest (AESIs)
9. Occurrence of immune-mediated adverse events (imAEs)
10. Occurrence of interruption and discontinuation of study drug(s) due to TEAE
11. Occurrence of laboratory abnormalities - Grade ≥3 per National Cancer Institute-Common Terminology Criteria for Adverse Events (NCI-CTCAE v5.0) including standard hematology, chemistry, urinalysis, and other lab tests
12. Occurrence of death due to TEAE
13. Concentrations of cemiplimab in serum
14. Concentrations of fianlimab in serum
15. Anti-drug antibodies (ADA) to fianlimab in serum over time
16. ADA to cemiplimab in serum over time
17. Percentage of patients with definitive surgery
18. Percentage of patients with cancelled surgery
19. Percentage of patients with delayed surgery
20. Completeness of resection (R0, R1, R2, Rx)
21. Length in delay of surgery
22. Type of surgery (lobectomy, sleeve lobectomy, bilobectomy, pneumonectomy, other)
23. Median length of hospital stay
24. Surgical approach (thoracotomy, minimally invasive, minimally invasive to thoracotomy)
25. Incidence of peri operative AE associated with surgery
26. Incidence of peri operative SAE associated with surgery
27. Incidence of post operative AE associated with surgery
28. Incidence of post operative SAE associated with surgery
29. Overall change in patient-reported global health status/QoL per European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30)
30. Overall change in patient-reported physical functioning per EORTC QLQ-C30
31. Overall change in patient-reported role functioning per EORTC QLQ-C30
32. Overall change in patient-reported chest pain per European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Lung Cancer 13 (EORTC QLQ-LC13)
33. Overall change in patient-reported dyspnea per EORTC QLQ-LC13
34. Overall change in patient-reported cough per EORTC QLQ-LC13
35. Overall change in patient-reported composite of chest pain, dyspnea, and cough per EORTC QLQ-LC13
36. Change in patient-reported general health status per EuroQoL 5-Dimensional 5-Level Scale (EQ-5D-5L) index
37. Change in patient-reported general health status per Visual analogue scale (VAS) scores
38. Time until definitive deterioration in patient-reported global health status/QoL per EORTC QLQ-C30
39. Time until definitive deterioration in patient-reported physical functioning per EORTC QLQ-C30
40. Time until definitive deterioration in patient-reported role functioning per EORTC QLQ-C30
41. Time until definitive deterioration in patient-reported chest pain per EORTC QLQ-LC13
42. Time until definitive deterioration in patient-reported dyspnea per EORTC QLQ-LC13
43. Time until definitive deterioration in patient-reported cough per EORTC QLQ-LC13
44. Time until definitive deterioration in patient-reported composite of chest pain, dyspnea and cough per EORTC QLQ-LC13

Investigational products

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

Test 3

Placebo 1

Auxiliary 4

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

Medical Affairs

Public contact point

Organisation

Regeneron Pharmaceuticals Inc.

Contact name

Medical Affairs

Third parties 9

Locations

5 EU/EEA countries · 65 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 89 files

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

Application history

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