A Trial to Learn if Fianlimab and Cemiplimab Are Safe and Work Better than Anti-PD1 Alone in Adult Participants with Resectable Stage 3 or 4 Melanoma

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

7 Oct 2024 → ongoing

Decision date (initial)

2024-10-07

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

Regeneron Pharmaceuticals Inc.

External identifiers

EU CT number

2022-502825-17-00

ClinicalTrials.gov

NCT06190951

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Efficacy, Pharmacokinetic, Dose response

To describe or report the treatment effect of the combination of fianlimab and cemiplimab to cemiplimab alone as peri-operative therapy in patients with resectable melanoma, as measured by pathological complete response (pCR) rate assessed by Blinded Independent Pathological Review (BIPR).

Secondary objectives 11

1. Assess pCR by local pathological review
2. Assess EFS
3. Assess Distant metastasis-free survival (DMFS) in stage III patients
4. Assess Overall survival (OS)
5. Assess the rate of major pathological response (MPR) by local pathological review and BIPR
6. Assess objective response rate (ORR) to neo-adjuvant treatment by investigator and Blinded Independent Central Review (BICR)
7. Assess time to recurrence of disease, as measured by relapse-free survival (RFS)
8. Assess safety and tolerability of neo-adjuvant and adjuvant therapy
9. To characterize the concentration of fianlimab and cemiplimab
10. Assess immunogenicity of fianlimab and cemiplimab
11. To evaluate the impact of treatment on functioning, symptoms, and quality of life per FACT-M Melanoma subscale, EORTC QLQ-C30, and EQ-5D-5L

Conditions and MedDRA coding

Melanoma

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 6

1. All patients must be either stage III (IIIB, IIIC, IIID) or stage IV (M1a, M1b, M1c) per American Joint Committee on Cancer (AJCC) 8th edition (Amin 2017) and have histologically confirmed cutaneous melanoma that is deemed completely surgically resectable in order to be eligible as described in the protocol.
2. Patients with stage III melanoma must have clinically detectable disease that is confirmed as malignant on the pathology report. The pathology report must be reviewed, signed and dated by the investigator; this process will be confirmed during the interactive voice response system (IVRS) process as described in the protocol.
3. Patients must be candidates for full resection with curative intent and must be able to be surgically rendered free of disease with negative margins on resected specimens at surgery. The treatment plan including date of surgery must be documented by the investigator prior to randomization.
4. All patients must undergo full disease staging through a complete physical examination and imaging studies within 4 weeks prior to randomization. Imaging must include a computer tomography (CT) scan of the chest, abdomen, pelvis (if the primary tumor is on the head/neck then include a CT scan of head/neck), and all known sites of previously resected disease (if applicable) and brain magnetic resonance imaging (MRI) (or brain CT with contrast allowed if MRI is contraindicated).
5. Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0 or 1
6. Note: Other protocol-defined inclusion criteria apply

Exclusion criteria 9

1. Primary uveal melanoma
2. Ongoing or recent (within 2 years) evidence of an autoimmune disease that required systemic treatment with immunosuppressive agents. The following are non-exclusionary: vitiligo, childhood asthma that has resolved, residual hypothyroidism that requires only hormone replacement, psoriasis not requiring systemic treatment.
3. Patients must not have received any prior systemic anti-cancer therapy for melanoma. Prior radiotherapy for melanoma is allowed if not given to a target lesion or, if given to a target lesion, there is pathological evidence of disease progression in the same lesion.
4. Uncontrolled infection with human immunodeficiency virus (HIV), hepatitis B (HBV) or hepatitis C virus (HCV) infection; or diagnosis of immunodeficiency that is related to or results in chronic infection as described in the protocol.
5. Use of immunosuppressive doses of corticosteroids (≥10mg of prednisone per day or equivalent) within 14 days of the first dose of study medication as described in the protocol.
6. Treatment with any anti-cancer therapy for malignancies other than melanoma, including immuno- therapy, chemotherapy, radiotherapy, or biological therapy in the 5 years prior to randomization as described in the protocol.
7. Participants with a history of myocarditis.
8. History or current evidence of significant (CTCAE grade ≥2) local or systemic infection (e. g., cellulitis, pneumonia, septicemia) requiring systemic antibiotic treatment within 2 weeks prior to the first dose of trial medication.
9. Note: Other protocol-defined exclusion criteria apply

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Pathological complete response (pCR) rate as assessed by Blinded Independent Pathological Review (BIPR)

Secondary endpoints 25

1. pCR rate as assessed by local pathologic review
2. Event-Free Survival (EFS)
3. Distant metastasis-free survival (DMFS)
4. Overall survival (OS)
5. Major pathological response (MPR) as assessed by BIPR
6. MPR rate as assessed by local pathologic review
7. Objective Response Rate (ORR) assessed by investigator per RECIST 1.1 criteria
8. ORR assessed by Blinded Independent Central Review (BICR) per RECIST 1.1 criteria
9. Relapse-free survival (RFS)
10. Occurrence of treatment-emergent adverse events (TEAEs)
11. Occurrence of immune-mediated adverse events (imAEs)
12. Occurrence of serious adverse events (SAEs)
13. Occurrence of adverse events of special interest (AESIs)
14. Occurrence of TEAEs resulting in death
15. Occurrence of interruption or discontinuation of study drug(s) due to TEAE.
16. Occurrence of cancellation of surgery due to TEAE or delay to surgery
17. Occurrence of laboratory abnormalities
18. Concentrations of fianlimab in serum
19. Concentrations of cemiplimab in serum
20. Anti-drug antibodies (ADA) in serum to fianlimab
21. ADA in serum to cemiplimab
22. Change from baseline in disease-related symptoms per Functional Assessment of Cancer Therapy-Melanoma (FACT-M) subscale
23. Change from baseline in functioning per European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (QoL) C30 (EORTC QLQ-C30)
24. Change from baseline in global health status/QoL per EORTC QLQ-C30
25. Change from baseline in overall health state per European Quality of Life Dimension 5 (EQ-5D-5L)

Investigational products

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

Test 4

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

Medical Affairs

Public contact point

Organisation

Regeneron Pharmaceuticals Inc.

Contact name

Medical Affairs

Third parties 8

Locations

8 EU/EEA countries · 78 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 50 files

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

Application history

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