A Study of Fianlimab, Cemiplimab, and Ipilimumab in People With Melanoma

NCT06594991 | Recruiting Phase 2 FDA Drug

• 1 other identifier: 24-166
• Study Type: interventional
• Target: 88
• Locations: 1 country
• Sites: 12

Brief Summary

The purpose of this study is to test whether the combination of fianlimab, cemiplimab, and ipilimumab is a safe and effective treatment that causes few or mild side effects for locally advanced or metastatic, unresectable, refractory melanoma.

Conditions

Advanced Melanoma

Keywords

Fianlimab; Cemiplimab; Ipilimumab; anti-PD-1 refractory melanoma; unresectable Stage III/IV melanoma; 24-166

Outcome Measures

Primary Outcomes (2)

• Determine best objective response rate (ORR) (cohort A)

  by RECIST v1.1

  6 weeks

• Determine best objective response rate (ORR) (cohort B)

  by RECIST v1.1

  6 weeks

Study Arms (2)

Refractory melanoma after PD-1 monotherapy (Cohort A)

EXPERIMENTAL

All patients will receive intravenous Fianlimab and Cemiplimab every three weeks continuously. Ipilimumab will be given every 6 weeks continuously. For all patients, fianlimab and Ccemiplimab will initially be co-administered and then followed by ipilimumab on D1 of each cycle per institutional standards.

Drug: Fianlimab; Drug: Cemiplimab; Drug: Ipilimumab

Refractory melanoma after combined PD-1 and LAG-3 blockade (Cohort B)

EXPERIMENTAL

All patients will receive intravenous Fianlimab and Cemiplimab every three weeks continuously. Ipilimumab will be given every 6 weeks continuously. For all patients, fianlimab and Ccemiplimab will initially be co-administered and then followed by ipilimumab on D1 of each cycle per institutional standards.

Drug: Fianlimab; Drug: Cemiplimab; Drug: Ipilimumab

Interventions

Fianlimab DRUG

Fianlimab IV given every three weeks

Refractory melanoma after PD-1 monotherapy (Cohort A); Refractory melanoma after combined PD-1 and LAG-3 blockade (Cohort B)

Cemiplimab DRUG

Cemiplimab IV given every three weeks

Refractory melanoma after PD-1 monotherapy (Cohort A); Refractory melanoma after combined PD-1 and LAG-3 blockade (Cohort B)

Ipilimumab DRUG

Ipilimumab will be give every 6 weeks continuously

Refractory melanoma after PD-1 monotherapy (Cohort A); Refractory melanoma after combined PD-1 and LAG-3 blockade (Cohort B)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age ≥ 18 years at the time of informed consent
• Patient/legal authorized representative (LAR) must be able to provide informed consent.
• Patient must have a histologically confirmed diagnosis of locally advanced unresectable stage III/IV or metastatic stage IV cutaneous or mucosal melanoma that has progressed on PD-1/PD-L1 therapy:
• o For Cohort A, the patient's melanoma must have progressed on prior PD-1 monotherapy
• For Cohort B, the patient's melanoma must have progressed on prior combination PD-1 + LAG-3 blockade
• Note: Intervening lines of targeted therapy, chemotherapy, bispecific (e.g. IMCgp100) and cell-based therapies are permitted between last ICI-based therapy and the start of study therapy
• Note: For cohort A, peptide and mRNA vaccines may have been combined with PD-1 monotherapy as long as no other checkpoint inhibitors were concomitantly administered. For cohort B, peptide and mRNA vaccines may have been combined with combined PD-1 + LAG-3 blockade as long as no other checkpoint inhibitors were concomitantly administered Note: Prior PD-1 monotherapy (Cohort A) or PD-1 and LAG-3 blockade (Cohort B) may have been given in the neoadjuvant or adjuvant setting as long as progression is documented within 3 months of the final dose neoadjuvant/adjuvant therapy
• Patients must have measurable disease as defined by RECIST v1.1 o Note: Lesions previously injected with Talimogene laherparepvec or other local therapies may not be selected as target lesions unless they have demonstrated subsequent growth after injection
• If a suitable archival tissue sample is available, the patient must be willing to have this specimen submitted for research. If an archival sample is not available, the patient is still a candidate for the trial, and every reasonable effort will be made to obtain a biopsy if deemed safe
• Eastern Cooperative Oncology Group (ECOG) performance status ≤ 1
• ° Adequate laboratory function at screening, defined as:
• ° Hemoglobin ≥ 10 gm/dL (≥ 6.2 mmol/L)
• ° Platelet count ≥ 100 × 10\^9 /L
• °Serum direct bilirubin ≤ 1.5 × ULN; AST and ALT ≤ 2.5 × ULN. (Total bilirubin \< 3 mg/dL for subjects with Gilbert's disease)
• No signs of active coronary ischemia, including ECG changes or elevated troponin if clinically indicated

You may not qualify if:

• Uveal melanoma
• Untreated central nervous system (CNS) metastases or leptomeningeal involvement; patients with brain metastases definitively treated with surgery or stereotactic radiosurgery (SRS) are permitted
• Receipt of the following prior therapies:
• For Cohort A: Any prior anti-LAG-3 (e.g., relatlimab) or CTLA-4 (e.g., ipilimumab) directed therapy, unless it was given in the adjuvant or neoadjuvant setting and the last dose was given more than three months prior to disease recurrence
• For Cohort B: Any prior CTLA-directed therapy (e.g., ipilimumab), unless it was given in the adjuvant or neoadjuvant setting and the last dose was given more than three months prior to disease recurrence
• Prior Grade 3 or greater neurologic toxicity associated with a prior line of ICI therapy
• Any prior myocarditis associated with ICI therapy
• Prior Grade 3 or greater colitis or enteritis requiring hospitalization
• Concurrent systemic steroid therapy higher than physiologic dose steroid replacement (\>7.5 mg/day of prednisone or equivalent), given within 14 days of starting treatment, or other immunosuppressive medications within 14 days of the start of treatment. Inhaled or topical steroids are permitted in the absence of active autoimmune disease.
• Receipt of a live vaccine within 30 days of planned start of study medication
• Significant infection requiring systemic antibiotics within 2 weeks of the planned start of study medication (e.g., pneumonia, cellulitis)
• Uncontrolled (i.e., unstable) concomitant medical condition or organ system dysfunction which, in the treating Investigator's opinion, could compromise the patient's safety or compliance with the study procedures.
• Other active, concurrent malignancy that requires ongoing systemic treatment or interferes with radiographic assessment of melanoma response as determined by the treating investigator
• History of severe hypersensitivity reactions to any unknown allergens or any components of the study drugs (active ingredients or excipients)
• Has uncontrolled infection with human immunodeficiency virus, hepatitis B, or hepatitis C infection; or has a diagnosis of immunodeficiency. Notes:

Sponsors & Collaborators

• Memorial Sloan Kettering Cancer Center: lead
• Regeneron Pharmaceuticals: collaborator

Study Sites (12)

Cedars-Sinai Medical Center

Los Angeles, California, 90048, United States

RECRUITING

Stanford University (Data Collection Only)

Stanford, California, 94305, United States

RECRUITING

Hartford Healthcare Alliance (Data Collection Only)

Hartford, Connecticut, 06102, United States

NOT YET RECRUITING

Memorial Sloan Kettering Basking Ridge (All Protocol Activities)

Basking Ridge, New Jersey, 07920, United States

RECRUITING

Hackensack Meridian Health (Data Collection Only)

Hackensack, New Jersey, 07601, United States

RECRUITING

Memorial Sloan Kettering Monmouth (All Protocol Activities)

Middletown, New Jersey, 07748, United States

RECRUITING

Memorial Sloan Kettering Bergen (Limited Protocol Activities)

Montvale, New Jersey, 07645, United States

RECRUITING

Memorial Sloan Kettering Suffolk - Commack (Limited Protocol Activities)

Commack, New York, 11725, United States

RECRUITING

Memorial Sloan Kettering Westchester (All Protocol Activities)

Harrison, New York, 10604, United States

RECRUITING

Memorial Sloan Kettering Cancer Center (All Protocol Activities)

New York, New York, 10065, United States

RECRUITING

Memorial Sloan Kettering Nassau (Limited Protocol Activities)

Uniondale, New York, 11553, United States

RECRUITING

MD Anderson Cancer Center (Data Collection Only)

Houston, Texas, 77030, United States

NOT YET RECRUITING

Related Links

• Memorial Sloan Kettering Cancer Center

MeSH Terms

Interventions

cemiplimab; Ipilimumab

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• James Smithy, MD

  Memorial Sloan Kettering Cancer Center

  PRINCIPAL INVESTIGATOR

Central Study Contacts

James Smithy, MD

CONTACT

646-888-6782; smithyj@mskcc.org

Michael Postow, MD

CONTACT

646-888-4589

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Patients will be enrolled in parallel across two independent cohorts, each with a nonrandomized two stage trial design. Cohort A (46 patients) will include patients whose melanoma progressed on prior anti-PD-1 monotherapy, and Cohort B (42 patients) will include patients whose melanoma has progressed on prior PD-1 and LAG-3 blockade.

Study Record Dates

• First Submitted: September 10, 2024
• First Posted: September 19, 2024
• Study Start: September 10, 2024
• Primary Completion (Estimated): September 1, 2027
• Study Completion (Estimated): September 1, 2027
• Last Updated: April 23, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will share

Locations

US (12)