Clinical Study of Fianlimab in Combination With Cemiplimab versus Pembrolizumab in Adolescent and Adult Patients With Previously Untreated Unresectable Locally Advanced or Metastatic Melanoma

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Regeneron Pharmaceuticals Inc.

Participant type

Pediatric, Patients

Age range

0-17 years, 18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

9 Nov 2022 → ongoing

Decision date (initial)

2024-04-22

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

Regeneron Pharmaceuticals Inc.

External identifiers

EU CT number

2023-505772-30-00

EudraCT number

2021-004453-23

ClinicalTrials.gov

NCT05352672

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Pharmacokinetic, Therapy, Efficacy, Safety

To demonstrate superiority of fianlimab + cemiplimab compared to pembrolizumab, as measured by progression-free survival (PFS)

Secondary objectives 10

1. To demonstrate superiority of fianlimab + cemiplimab compared to pembrolizumab, as measured by overall survival (OS)
2. To demonstrate superiority in objective response rate (ORR) with fianlimab + cemiplimab compared to pembrolizumab
3. To assess ORR, PFS, and OS with fianlimab + cemiplimab compared to cemiplimab to inform the contribution of each component
4. To assess immunogenicity of fianlimab and cemiplimab
5. To assess impact of fianlimab + cemiplimab on physical functioning and role functioning and global health status/quality of life, as compared to pembrolizumab in adults
6. To assess safety and tolerability of treatment in patients 12 to <18 years of age
7. To assess ORR, PFS, and OS with treatment in patients 12 to <18 years of age
8. To assess the safety and tolerability of fianlimab + cemiplimab compared to pembrolizumab and to cemiplimab
9. To characterize pharmacokinetics (PK) of fianlimab and cemiplimab using sparse PK sampling in patients aged ≥12 years
10. To assess the DoR with fianlimab + cemiplimab compared to pembrolizumab.

Conditions and MedDRA coding

Melanoma

Regulatory references

Scientific advice from competent authorities

European Medicines Agency

Plan to share IPD

Yes

IPD plan description

All Individual Patient Data (IPD) that underlie publicly available results will be considered for sharing

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 5

1. Age ≥12 years on the date of providing informed consent
2. Patients with histologically confirmed unresectable Stage III and Stage IV (metastatic) melanoma (AJCC, 8th revised edition) who have not received prior systemic therapy for advanced unresectable disease: a. Patients who received adjuvant and/or neoadjuvant systemic therapies are eligible if they did not have evidence of progression or recurrence of disease and/or discontinued due to occurrence of unmanageable imAEs ≥ grade 3 (with the exclusion of endocrinopathies which are fully controlled by hormone replacement) while on such therapies. Also, patients must have had a treatment-free and disease-free interval of >6 months. b. Patients with acral and mucosal melanomas are eligible. Accrual of these patients is limited to approximately 10% of the total population enrolled. Accrual will be limited to 10% of the total population.
3. Measurable disease per RECIST v1.1: a. Previously irradiated lesions can only be counted as target lesions if they have been demonstrated to progress and no other target lesion is available. b. Cutaneous lesions should be evaluated as non-target lesions
4. Performance status: a. For adult patients: Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0 or 1. b. For pediatric patients: Karnofsky performance status ≥70 (patients ≥16 years) or Lansky performance status ≥70 (patients ≤16 years)
5. Anticipated life expectancy of at least 3 months

Exclusion criteria 10

1. 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. 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
4. Unknown BRAF V600 mutation status as described in the protocol
5. Systemic immune suppression: a. Use of immunosuppressive doses of corticosteroids (>10mg of prednisone per day or equivalent) within 14 days of the first dose of study medication. Physiologic replacement doses are allowed up to and including 10mg of prednisone/day or equivalent. Inhaled or topical steroids are permitted, if they are not for treatment of an autoimmune disorder. b. Other clinically relevant forms of systemic immune suppression
6. Treatment with other anti-cancer therapy including immuno- therapy, chemotherapy, major surgery or biological therapy within 21 days prior to the first dose of trial treatment. Adjuvant hormonotherapy used for breast cancer or other hormone-sensitive cancers in long term remission is allowed.
7. History or current evidence of significant (CTCAE Grade ≥2) local or systemic infection (e. g., cellulitis, pneumonia, septicemia) requiring systemic antibiotic treatment within 14 days prior to the first dose of trial medication.
8. Active or untreated brain metastases or spinal cord compression. Patients with leptomeningeal disease are excluded. Patients with known brain metastases are eligible if they: a. Received radiotherapy or another appropriate standard therapy for the brain metastases; b. Have neurologically returned to baseline (except for residual signs and symptoms related to the CNS treatment) for at least 14 days prior to enrollment; c. Did not require immunosuppressive doses of corticosteroids therapy (>10mg of prednisone per day or equivalent) in the 14 days prior to enrollment; d. Are asymptomatic with a single untreated brain metastasis <10 mm in size
9. Participants with a history of myocarditis
10. Other protocol-defined Inclusion/ Exclusion criteria apply

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Progression-free survival (PFS)

Secondary endpoints 28

1. Overall survival (OS)
2. Objective response rate (ORR)
3. Disease control rate (DCR)
4. Duration of response (DoR)
5. PFS per investigator assessment
6. Incidence of Adverse Events (AEs)
7. Occurrence of interruption and discontinuation of study drug(s) due to AEs
8. TEAEs leading to death
9. Incidence of laboratory abnormalities
10. Concentrations of cemiplimab in serum
11. Concentrations of fianlimab in serum
12. Incidence of anti-drug antibodies (ADA) to fianlimab over time
13. Titer of anti-drug antibodies (ADA) to fianlimab over time
14. Incidence of ADA to cemiplimab over time
15. Titer of ADA to cemiplimab over time
16. Incidence of neutralizing antibodies (NAb) to fianlimab over time
17. Incidence of NAb to cemiplimab over time
18. Patient-reported outcomes (PROs) as measured by European Organization for Research and Treatment of Cancer Quality of Life Questionnaire C30 (EORTC QLQ-C30)
19. PROs as measured by EQ-5D-5L
20. PROs as measured by Functional Assessment of Cancer Therapy (FACT)-melanoma (melanoma subscale only)
21. PROs as measured by Patient Global Impression of Severity (PGIS)
22. PROs as measured by Patient Global Impression of Change (PGIC)
23. Change in physical functioning per EORTC QLQ-C30
24. Change in role functioning per EORTC QLQ-C30
25. Change in global health status/quality of life (GHS/QoL) per EORTC QLQ-C30
26. Change in physical functioning per EORTC QLQ-C30
27. Change in role functioning per EORTC QLQ-C30
28. Change in GHS/QoL per EORTC QLQ-C30

Investigational products

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

Test 2

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 10

Locations

12 EU/EEA countries · 117 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 191 files

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

Application history

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