FIANLIMAB for Malignant melanoma|Unresectable locally advanced or metastatic melanoma

Inclusion criteria

• {"criterion_text":"- Age ≥12 years on the date of providing informed consent\n- 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.\n- 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\n- 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)\n- Anticipated life expectancy of at least 3 months"}

Exclusion criteria

• {"criterion_text":"- Uveal melanoma\n- 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.\n- 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\n- Unknown BRAF V600 mutation status as described in the protocol\n- 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\n- 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.\n- 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.\n- 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\n- Participants with a history of myocarditis\n- Other protocol-defined Inclusion/ Exclusion criteria apply"}

Primary endpoints

• {"endpoint_text":"- Progression-free survival (PFS)","definition_or_measurement_approach":"To demonstrate superiority of fianlimab + cemiplimab compared to pembrolizumab, as measured by progression-free survival (PFS)."}

Secondary endpoints

• {"endpoint_text":"- Overall survival (OS)","definition_or_measurement_approach":""}
• {"endpoint_text":"- Objective response rate (ORR)","definition_or_measurement_approach":""}
• {"endpoint_text":"- Disease control rate (DCR)","definition_or_measurement_approach":""}
• {"endpoint_text":"- Duration of response (DoR)","definition_or_measurement_approach":""}
• {"endpoint_text":"- PFS per investigator assessment","definition_or_measurement_approach":""}
• {"endpoint_text":"- Incidence of Adverse Events (AEs)","definition_or_measurement_approach":""}
• {"endpoint_text":"- Occurrence of interruption and discontinuation of study drug(s) due to AEs","definition_or_measurement_approach":""}
• {"endpoint_text":"- TEAEs leading to death","definition_or_measurement_approach":""}
• {"endpoint_text":"- Incidence of laboratory abnormalities","definition_or_measurement_approach":""}
• {"endpoint_text":"- Concentrations of cemiplimab in serum","definition_or_measurement_approach":"Pharmacokinetic measurement (sparse PK sampling) in patients aged ≥12 years"}
• {"endpoint_text":"- Concentrations of fianlimab in serum","definition_or_measurement_approach":"Pharmacokinetic measurement (sparse PK sampling) in patients aged ≥12 years"}
• {"endpoint_text":"- Incidence of anti-drug antibodies (ADA) to fianlimab over time","definition_or_measurement_approach":""}
• {"endpoint_text":"- Titer of anti-drug antibodies (ADA) to fianlimab over time","definition_or_measurement_approach":""}
• {"endpoint_text":"- Incidence of ADA to cemiplimab over time","definition_or_measurement_approach":""}
• {"endpoint_text":"- Titer of ADA to cemiplimab over time","definition_or_measurement_approach":""}
• {"endpoint_text":"- Incidence of neutralizing antibodies (NAb) to fianlimab over time","definition_or_measurement_approach":""}
• {"endpoint_text":"- Incidence of NAb to cemiplimab over time","definition_or_measurement_approach":""}
• {"endpoint_text":"- Patient-reported outcomes (PROs) as measured by European Organization for Research and Treatment of Cancer Quality of Life Questionnaire C30 (EORTC QLQ-C30)","definition_or_measurement_approach":"PRO instrument: EORTC QLQ-C30"}
• {"endpoint_text":"- PROs as measured by EQ-5D-5L","definition_or_measurement_approach":"PRO instrument: EQ-5D-5L"}
• {"endpoint_text":"- PROs as measured by Functional Assessment of Cancer Therapy (FACT)-melanoma (melanoma subscale only)","definition_or_measurement_approach":"PRO instrument: FACT-Melanoma (melanoma subscale)"}
• {"endpoint_text":"- PROs as measured by Patient Global Impression of Severity (PGIS)","definition_or_measurement_approach":"PRO instrument: PGIS"}
• {"endpoint_text":"- PROs as measured by Patient Global Impression of Change (PGIC)","definition_or_measurement_approach":"PRO instrument: PGIC"}
• {"endpoint_text":"- Change in physical functioning per EORTC QLQ-C30","definition_or_measurement_approach":"Change assessed using EORTC QLQ-C30 physical functioning scale"}
• {"endpoint_text":"- Change in role functioning per EORTC QLQ-C30","definition_or_measurement_approach":"Change assessed using EORTC QLQ-C30 role functioning scale"}
• {"endpoint_text":"- Change in global health status/quality of life (GHS/QoL) per EORTC QLQ-C30","definition_or_measurement_approach":"Change assessed using EORTC QLQ-C30 global health status/QoL"}
• {"endpoint_text":"- Change in physical functioning per EORTC QLQ-C30","definition_or_measurement_approach":"Change assessed using EORTC QLQ-C30 physical functioning scale"}
• {"endpoint_text":"- Change in role functioning per EORTC QLQ-C30","definition_or_measurement_approach":"Change assessed using EORTC QLQ-C30 role functioning scale"}
• {"endpoint_text":"- Change in GHS/QoL per EORTC QLQ-C30","definition_or_measurement_approach":"Change assessed using EORTC QLQ-C30 global health status/QoL"}

Methods

• Patient letters (site-specific patient letter documents in multiple languages indicated: en, nl, fr) — channel: direct letter to potential participants; target: patients with metastatic/unresectable melanoma.
• Printed recruitment materials: trifold and multifold leaflets (documents Trifold/Multifold in multiple languages) — channel: clinic distribution and patient-facing sites; target: patients/public.
• Website materials (documents Website_en/nl/fr) — channel: sponsor/site websites; target: patients and public; country-specific web materials provided for multiple Member States.
• GP/clinician letters (GP Letter document) — channel: primary care/clinician referral; target: healthcare professionals to support referral.
• Third-party recruitment services: Jumo Health USA Inc. listed with sponsor duty 'Subject recruitment' (third-party conducting recruitment activities).

Belgium

Earliest CTIS Part Ii Submission Date

16-02-2024

Latest Decision Or Authorization Date

28-03-2024

Processing Time Days

41

Number Of Sites

4

Number Of Participants

16

France

Earliest CTIS Part Ii Submission Date

16-02-2024

Latest Decision Or Authorization Date

20-03-2024

Processing Time Days

33

Number Of Sites

18

Number Of Participants

87

Hungary

Earliest CTIS Part Ii Submission Date

16-02-2024

Latest Decision Or Authorization Date

08-03-2024

Processing Time Days

21

Number Of Sites

4

Number Of Participants

40

Romania

Earliest CTIS Part Ii Submission Date

16-02-2024

Latest Decision Or Authorization Date

12-03-2024

Processing Time Days

25

Number Of Sites

10

Number Of Participants

120

Poland

Earliest CTIS Part Ii Submission Date

16-02-2024

Latest Decision Or Authorization Date

25-03-2024

Processing Time Days

38

Number Of Sites

5

Number Of Participants

38

Ireland

Earliest CTIS Part Ii Submission Date

16-02-2024

Latest Decision Or Authorization Date

07-03-2024

Processing Time Days

20

Number Of Sites

4

Number Of Participants

30

Italy

Earliest CTIS Part Ii Submission Date

16-02-2024

Latest Decision Or Authorization Date

25-03-2024

Processing Time Days

38

Number Of Sites

25

Number Of Participants

70

Austria

Earliest CTIS Part Ii Submission Date

16-02-2024

Latest Decision Or Authorization Date

22-04-2024

Processing Time Days

66

Number Of Sites

4

Number Of Participants

13

Netherlands

Earliest CTIS Part Ii Submission Date

16-02-2024

Latest Decision Or Authorization Date

07-03-2024

Processing Time Days

20

Number Of Sites

2

Number Of Participants

9

Spain

Earliest CTIS Part Ii Submission Date

16-02-2024

Latest Decision Or Authorization Date

11-03-2024

Processing Time Days

24

Number Of Sites

28

Number Of Participants

21

Germany

Earliest CTIS Part Ii Submission Date

16-02-2024

Latest Decision Or Authorization Date

11-03-2024

Processing Time Days

24

Number Of Sites

23

Number Of Participants

106

Czechia

Earliest CTIS Part Ii Submission Date

16-02-2024

Latest Decision Or Authorization Date

12-03-2024

Processing Time Days

25

Number Of Sites

3

Number Of Participants

12

Primary sponsor

Full Name

Regeneron Pharmaceuticals Inc.

Organisation Type

Pharmaceutical company

Country Of Registered Address

United States

Contract research organisations

Name

Icon (Lr) Limited

Responsibilities

Sponsor duties codes: 1, 14, 2, 5 (roles as listed in CTIS entry)

Name

Parexel International (IRL) Limited

Responsibilities

Sponsor duties code: 5 (role as listed in CTIS entry)

Third parties

• {"country":"United States","full_name":"FACIT.Org Inc.","duties_or_roles":"eCOA","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Medidata Solutions Inc.","duties_or_roles":"sponsorDuties code: 6","organisation_type":"Non-Pharmaceutical company"}
• {"country":"United States","full_name":"Q Squared Solutions LLC","duties_or_roles":"sponsorDuties code: 4","organisation_type":"Laboratory/Research/Testing facility"}
• {"country":"United States","full_name":"Yprime LLC","duties_or_roles":"eCOA","organisation_type":"Non-Pharmaceutical company"}
• {"country":"Belgium","full_name":"European Organisation For Research And Treatment Of Cancer","duties_or_roles":"eCOA","organisation_type":"Patient organisation/association"}
• {"country":"Ireland","full_name":"Icon (Lr) Limited","duties_or_roles":"sponsorDuties codes: 1, 14, 2, 5","organisation_type":"Non-Pharmaceutical company"}
• {"country":"Ireland","full_name":"Parexel International (IRL) Limited","duties_or_roles":"sponsorDuties code: 5","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Perceptive Informatics Inc.","duties_or_roles":"sponsorDuties codes: 14, 3","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Ventana Medical Systems Inc.","duties_or_roles":"sponsorDuties codes: 13, 15 (Specialty Laboratory)","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Jumo Health USA Inc.","duties_or_roles":"Subject recruitment","organisation_type":"Hospital/Clinic/Other health care facility"}