Fianlimab and Cemiplimab Versus Pembrolizumab in Advanced or Metastatic Melanoma

What is the Purpose of this Study?

This study focuses on individuals with advanced or metastatic melanoma (a type of skin cancer). The purpose of the study is to evaluate an investigational drug called REGN3767 (fianlimab), an anti-LAG3 antibody when combined with another investigational drug called REGN2810 (cemiplimab), an anti-PD1 antibody. Researchers aim to determine how effective the combination of fianlimab and cemiplimab is in treating melanoma, compared to a single agent anti-PD1 drug called pembrolizumab (approved by the U.S. Food and Drug Administration for the treatment of melanoma in adults) or cemiplimab. The study will also examine any side effects; how much of the drugs are in the blood at different times; and whether the body makes antibodies against the drugs. Participants may receive cemiplimab alone, fianlimab and cemiplimab in combination, or pembrolizumab alone.

Eligibility

Age ≥12 years on the date of providing informed consent
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

Key Inclusion Criteria:

Age ≥12 years on the date of providing informed consent
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
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. Accrual of these patients is limited to approximately 10% of the total population enrolled in each of the Phase 2 and Phase 3 parts of the study.
Patients with acral and mucosal melanomas are eligible. Combined accrual will be limited to 10% of the total population enrolled in the Phase 3 part of the study.
Measurable disease per RECIST v1.1
Previously irradiated lesions can only be counted as target lesions if they have been demonstrated to progress and no other target lesion is available
Cutaneous lesions should be evaluated as non-target lesions
Performance status:
For adult patients: Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0 or 1
For pediatric patients: Karnofsky performance status ≥70 (patients ≥16 years) or Lansky performance status ≥70 (patients ≤16 years)
Anticipated life expectancy of at least 3 months

Key Exclusion Criteria:

Uveal melanoma
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.
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
Unknown v-Raf murine sarcoma viral oncogene homolog B1 (BRAF) V600 mutation status as described in the protocol
Systemic immune suppression:
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.
Other clinically relevant forms of systemic immune suppression
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.
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.
Participants with a history of myocarditis.
Active or untreated brain metastases or spinal cord compression. Patients with leptomeningeal disease are excluded. Patients with known brain metastases are eligible if they:
Received radiotherapy or another appropriate standard therapy for the brain metastases,
Have neurologically returned to baseline (except for residual signs and symptoms related to the CNS treatment) for at least 14 days prior to enrollment
Did not require immunosuppressive doses of corticosteroids therapy (>10mg of prednisone per day or equivalent) in the 14 days prior to enrollment
Are asymptomatic with a single untreated brain metastasis <10 mm in size

Show less

Where can I participate?

Cedars-Sinai Cancer at The Angeles Clinic and Research Institute : Saba Mukarram

More about this Clinical Trial

What is the full name of this clinical trial?

R3767-ONC-2011: A Phase 3 Trial of Fianlimab +Cemiplimab Versus Pembrolizumab in Patients with Previously Untreated Unresectable Locally Advanced Or Metastatic Melanoma

Study Details

Disease Type/Condition

Melanoma

Principal Investigator

Hamid, Omid

Co-Investigators

Ani Balmanoukian, Cathie T Chung, Inderjit Mehmi, Iryna Singh, Justin Moyers, Kristopher Wentzel, Navid Hafez, Vi K. Chiu

Age Group

Adult

Phase

III

IRB Number

STUDY00002105

ClinicalTrials.gov ID

NCT05352672

Key Eligibility

ClinicalTrials.gov

How do I learn more about this study?

Name

Saba Mukarram

Phone

+1 310-231-2181

MukarramS@cshs.org