Clinical study of Fianlimab in combination with Cemiplimab in patients with previously untreated unresectable locally advanced or metastatic melanoma.

Phase 1

• Conditions: Cutaneous Melanoma; MedDRA version: 21.1Level: PTClassification code 10025650Term: Malignant melanomaSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2021-004453-23-PL
• Lead Sponsor: Regeneron Pharmaceuticals, Inc.

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2022-04-28
• Last Update Posted: 15 April 2024

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 1590

Inclusion Criteria

1. Age =12 years on the date of providing informed consent. Note:
Patients who are <18 years will be included in the territories, where accepted, per local laws and regulations.
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 irAEs = 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 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.

Please note other protocol-defined Inclusion criteria apply

Are the trial subjects under 18? yes
Number of subjects for this age range: 6
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 1290
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 294

Exclusion Criteria

Medical conditions:
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. Patients with BRAF-mutated melanoma who present with symptoms of rapidly progressive disease and are considered by Investigator's assessment as likely to benefit from upfront treatment with BRAF/MEK-inhibitors should not be enrolled in the study.
Prior/concomitant therapy:
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, provided 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, radiotherapy, major surgery or biological therapy within 3 weeks 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.
Other comorbidities:
7. 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.
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.
Note: Patients who are asymptomatic single untreated brain metastasis <10 mm in size are eligible.
9. Adolescent patients (=12 to <18 years old) with body weight <40 kg.

Other protocol-defined Exclusion criteria apply

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified