Clinical trial NCT06190951: A Trial to Learn if Fianlimab and Cemiplimab Are Safe and Work Better Than Anti-PD1 Alone in Adult Participants With Resectable Stage 3 or 4 Melanoma
Official title: A Phase 2 Peri-operative Trial of Fianlimab and Cemiplimab Compared With Anti-PD1 Alone in Patients With Resectable Stage III and IV Melanoma
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Melanoma
Keywords: Skin cancer
Fully resectable stage III melanoma
Fully resectable stage IV melanoma
Lead sponsor: Regeneron Pharmaceuticals
Sponsor class: INDUSTRY
First posted: 2024-01-05
Enrollment: 150
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This study is researching an experimental drug called REGN3767, also known as fianlimab (R3767), when combined with another medication called cemiplimab (each individually called a "study drug" or called "study drugs" when combined) compared with cemiplimab alone. These types of immunotherapy study drugs are collectively known as immune checkpoint inhibitors. Immunotherapies are treatments that use the immune system to recognize and kill cancer cells. The study is focused on participants with a type of skin cancer known as melanoma.

The objective of this study is to see if the combination of fianlimab and cemiplimab is an effective treatment compared to cemiplimab in participants with high-risk, resectable melanoma. Participants will receive treatment before surgery, undergo resection, and then will have the option to continue treatment after resection.

The study is looking at several other research questions, including:

* What side effects may happen from receiving the study drug(s).
* How much study drug(s) is in the blood at different times.
* Whether the body makes antibodies against the study drug(s) (which could make the drug less effective or could lead to side effects). Antibodies are proteins that are naturally found in the blood stream that fight infections.
* How administering the study drugs might improve quality of life.


Eligibility criteria: Key Inclusion Criteria:

1. All patients must be either stage III (IIIB, IIIC, IIID) or stage IV (M1a, M1b, M1c) per American Joint Committee on Cancer (AJCC) 8th edition (Amin 2017) and have histologically confirmed cutaneous melanoma that is deemed completely surgically resectable in order to be eligible as described in the protocol.
2. Patients with stage III melanoma must have clinically detectable disease that is confirmed as malignant on the pathology report. The pathology report must be reviewed, signed and dated by the investigator; this process will be confirmed during the interactive voice response system (IVRS) process as described in the protocol.
3. Patients must be candidates for full resection with curative intent and must be able to be surgically rendered free of disease with negative margins on resected specimens at surgery. The treatment plan including date of surgery must be documented by the investigator prior to randomization.
4. All patients must undergo full disease staging through a complete physical examination and imaging studies within 4 weeks prior to randomization. Imaging must include a computer tomography (CT) scan of the chest, abdomen, pelvis (if the primary tumor is on the head/neck then include a CT scan of head/neck), and all known sites of previously resected disease (if applicable) and brain magnetic resonance imaging (MRI) (or brain CT with contrast allowed if MRI is contraindicated).
5. Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0 or 1

Key Exclusion Criteria:

Medical conditions:

1. Primary 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. Patients must not have received any prior systemic anti-cancer therapy for melanoma. Prior radiotherapy for melanoma is allowed if not given to a target lesion or, if given to a target lesion, there is pathological evidence of disease progression in the same lesion.
4. 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 as described in the protocol.

   Prior/concomitant therapy:
5. Use of immunosuppressive doses of corticosteroids (≥10mg of prednisone per day or equivalent) within 14 days of the first dose of study medication as described in the protocol.
6. Treatment with any anti-cancer therapy for malignancies other than melanoma, including immuno- therapy, chemotherapy, radiotherapy, or biological therapy in the 5 years prior to randomization as described in the protocol.

   Other comorbidities:
7. Participants with a history of myocarditis.
8. 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.

Note: Other protocol-defined inclusion/ exclusion criteria apply

Primary outcomes:
measure: Pathological complete response (pCR) rate as assessed by Blinded Independent Pathological Review (BIPR)
timeFrame: Up to 1 year
Secondary outcomes:
measure: pCR rate as assessed by local pathologic review
timeFrame: Up to 1 year
measure: Event-Free Survival (EFS)
timeFrame: Up to 4 years
measure: Distant metastasis-free survival (DMFS)
timeFrame: Up to 4 years
measure: Overall survival (OS)
timeFrame: Up to 4 years
measure: Major pathological response (MPR) as assessed by BIPR
timeFrame: Up to 4 years
measure: MPR rate as assessed by local pathologic review
timeFrame: Up to 4 years
measure: Objective Response Rate (ORR) assessed by investigator per RECIST 1.1 criteria
timeFrame: Up to 4 years
measure: ORR assessed by Blinded Independent Central Review (BICR) per RECIST 1.1 criteria
timeFrame: Up to 4 years
measure: Relapse-free survival (RFS)
timeFrame: Up to 4 years
measure: Occurrence of treatment-emergent adverse events (TEAEs)
timeFrame: 90 days following last dose of study drug, approximately 4 years
measure: Occurrence of immune-mediated adverse events (imAEs)
timeFrame: 90 days following last dose of study drug, approximately 4 years
measure: Occurrence of serious adverse events (SAEs)
timeFrame: 90 days following last dose of study drug, approximately 4 years
measure: Occurrence of adverse events of special interest (AESIs)
timeFrame: 90 days following last dose of study drug, approximately 4 years
measure: Occurrence of TEAEs resulting in death
timeFrame: 90 days following last dose of study drug, approximately 4 years
measure: Occurrence of interruption or discontinuation of study drug(s) due to TEAE.
timeFrame: 90 days following last dose of study drug, approximately 4 years
measure: Occurrence of cancellation of surgery due to TEAE or delay to surgery
timeFrame: 90 days following last dose of study drug, approximately 4 years
measure: Occurrence of laboratory abnormalities
timeFrame: 90 days following last dose of study drug, approximately 4 years
measure: Concentrations of fianlimab in serum
timeFrame: Up to 4 years
measure: Concentrations of cemiplimab in serum
timeFrame: Up to 4 years
measure: Anti-drug antibodies (ADA) in serum to fianlimab
timeFrame: Up to 4 years
measure: ADA in serum to cemiplimab
timeFrame: Up to 4 years
measure: Change from baseline in disease-related symptoms per Functional Assessment of Cancer Therapy-Melanoma (FACT-M) subscale
timeFrame: Up to 4 years
measure: Change from baseline in functioning per European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (QoL) C30 (EORTC QLQ-C30)
timeFrame: Up to 4 years
measure: Change from baseline in global health status/QoL per EORTC QLQ-C30
timeFrame: Up to 4 years
measure: Change from baseline in overall health state per European Quality of Life Dimension 5 (EQ-5D-5L)
timeFrame: Up to 4 years
Other outcomes:
Locations:
city: La Jolla
country: United States
facility: UC San Diego
state: California
city: Los Angeles
country: United States
facility: USC Norris Comprehensive Cancer Center
state: California
city: Newport Beach
country: United States
facility: Hoag Family Cancer Institute
state: California
city: San Francisco
country: United States
facility: California Pacific Medical Center Research Institute
state: California
city: San Francisco
country: United States
facility: University of California San Francisco (UCSF)
state: California
city: Santa Monica
country: United States
facility: St John's Cancer Institute
state: California
city: Hartford
country: United States
facility: Hartford Hospital
state: Connecticut
city: Atlanta
country: United States
facility: Emory Healthcare, Emory Clinic
state: Georgia
city: Evanston
country: United States
facility: NorthShore University HealthSystem
state: Illinois
city: Worcester
country: United States
facility: University of Massachusetts Chan Medical School
state: Massachusetts
city: Saint Louis
country: United States
facility: Washington University School of Medicine
state: Missouri
city: New Brunswick
country: United States
facility: Rutgers Cancer Institute of New Jersey
state: New Jersey
city: Lake Success
country: United States
facility: Northwell Health Cancer Institute
state: New York
city: Durham
country: United States
facility: Duke Cancer Institute, University Hospital
state: North Carolina
city: Cleveland
country: United States
facility: Seidman Cancer Center
state: Ohio
city: Cleveland
country: United States
facility: Cleveland Clinic Foundation
state: Ohio
city: Philadelphia
country: United States
facility: Thomas Jefferson University Hospital
state: Pennsylvania
city: Knoxville
country: United States
facility: University of Tennessee Medical Center
state: Tennessee
city: Houston
country: United States
facility: University of Texas MD Anderson Cancer Center
state: Texas
city: Charlottesville
country: United States
facility: University of Virginia
state: Virginia
city: Westmead
country: Australia
facility: Westmead Hospital
state: New South Wales
city: Wollstonecraft
country: Australia
facility: Melanoma Institute of Australia
state: New South Wales
city: Woodville
country: Australia
facility: The Queen Elizabeth Hospital
state: South Australia
city: Melbourne
country: Australia
facility: Peter MacCallum Cancer Centre
state: Victoria
city: Nedlands
country: Australia
facility: One Clinical Research at Hollywood Private Hospital
state: Western Australia
city: Montreal
country: Canada
facility: Centre Hospitalier de l'Universite de Montreal (CHUM)
state: Quebec
city: Quebec City
country: Canada
facility: CHU de Quebec - Universite Laval
state: Quebec
city: Dijon
country: France
facility: CHU-Dijon
state: Burgundy
city: Bordeaux
country: France
facility: Chu De Bordeaux
state: Gironde
city: Paris
country: France
facility: Saint Louis Hospital
state: Ile De France
city: Villejuif
country: France
facility: Gustave Roussy
state: Ile De France
city: Caen
country: France
facility: Centre Francois Baclesse
state: Normandy
city: Boulogne
country: France
facility: Hopital Ambroise Pare
city: Clermont Ferrand
country: France
facility: CHU Estaing
city: Lille
country: France
facility: Regional University Hospital of Lille 2208
city: Marseille
country: France
facility: Hopital Timone
city: Nice
country: France
facility: Centre Hospitalier Universitaire De Nice Hopital De L Archet
city: Giessen
country: Germany
facility: University Hospital Giessen
state: Hessen
city: Leipzig
country: Germany
facility: Universitatsklinikum Leipzig, AoR
state: Saxony
city: Berlin
country: Germany
facility: Charite University Medicine
city: Cona
country: Italy
facility: Azienda Ospedaliero-Universitaria Ferrara
state: Ferrara
city: Pisa
country: Italy
facility: U.O. Oncologia Medica 2 Universitaria, Azienda Ospedaliero Universitaria Pisana
city: Barcelona
country: Spain
facility: Vall d'Hebron Hospital
city: Barcelona
country: Spain
facility: Hospital Clinic de Barcelona
city: Salamanca
country: Spain
facility: Hospital Clinico Universitario de Salamanca
Study officials:
affiliation: Regeneron Pharmaceuticals
name: Clinical Trial Management
role: STUDY_DIRECTOR
References: