Clinical Study of Fianlimab in Combination With Cemiplimab Versus Pembrolizumab in Adolescent and Adult Patients With Previously Untreated Unresectable Locally Advanced or Metastatic Melanoma

Melanoma Clinical Trial

Official title:

A Phase 3 Trial of Fianlimab (REGN3767, Anti-LAG-3) + Cemiplimab Versus Pembrolizumab in Patients With Previously Untreated Unresectable Locally Advanced or Metastatic Melanoma

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05352672
• Other study ID #: R3767-ONC-2011
• Secondary ID: 2021-004453-2320
• Status: Recruiting
• Phase: Phase 3
• Start date: July 14, 2022
• Est. completion date: August 31, 2032

Study information

• Verified date: June 2024
• Source: Regeneron Pharmaceuticals
• Contact: Clinical Trials Administrator
• Phone: 844-734-6643
• Email: clinicaltrials[@]regeneron.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This study is researching an experimental drug called REGN3767, also known as fianlimab (R3767), when combined with another medication called REGN2810, also known as cemiplimab (each individually called a "study drug" or called "study drugs" when combined). The study is focused on patients with a type of skin cancer known as melanoma. The aims of the study are to see how effective the combination of fianlimab and cemiplimab are in treating the melanoma skin cancer, in comparison with a medication, pembrolizumab, approved for the treatment of melanoma skin cancer in adults, and to observe any similarities, or differences, in how the study drugs work in adolescent participants compared with adult participants. The study is looking at several other research questions, including: - What side effects may happen from receiving the study drugs - How much study drug is in the blood at different times - Whether the body makes antibodies against the study drugs (which could make the drugs 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

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 1590
• Est. completion date: August 31, 2032
• Est. primary completion date: March 3, 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 12 Years and older

Eligibility

Key Inclusion Criteria:

1. Age =12 years on the date of providing informed consent

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

1. 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.

2. 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

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

2. Cutaneous lesions should be evaluated as non-target lesions

4. Performance status:

1. For adult patients: Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0 or 1

2. 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

Key Exclusion Criteria:

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 as described in the protocol

5. Systemic immune suppression:

1. 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.

2. Other clinically relevant forms of systemic immune suppression

6. 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.

7. 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.

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:

1. Received radiotherapy or another appropriate standard therapy for the brain metastases,

2. Have neurologically returned to baseline (except for residual signs and symptoms related to the CNS treatment) for at least 14 days prior to enrollment

3. Did not require immunosuppressive doses of corticosteroids therapy (>10mg of prednisone per day or equivalent) in the 14 days prior to enrollment

4. Are asymptomatic with a single untreated brain metastasis <10 mm in size Note: Other protocol-defined Inclusion/ Exclusion criteria apply

Related Conditions & MeSH terms

• Melanoma

Intervention

Drug:
• Fianlimab
Intravenous (IV) infusion
• Cemiplimab
IV infusion
• Pembrolizumab
IV infusion
• Placebo
IV infusion

Locations

Country	Name	City	State
Argentina	DIABAID - Instituto de Asistencia Integral en Diabetes	Buenos Aires
Argentina	Fundacion Cenit para la Investigacion en Neurociencias	Buenos Aires
Argentina	Clinica Adventista Belgrano	Caba
Argentina	Fundacion CENIT Centro Medico de Neurociencias	Ciudad Autonoma de Buenos Aires
Argentina	Instituto de Oncologia de Rosario	Rosario
Argentina	Centro Medico San Roque	San Miguel de Tucuman
Australia	Calvary North Adelaide Hospital	Adelaide
Australia	Barwon Health Andrew Love Cancer Centre, University Hospital Geelong	Geelong
Australia	Icon Cancer Centre Hobart	Hobart
Australia	The Alfred Hospital	Melbourne
Australia	Gold Coast University Hospital	Southport
Australia	The Townsville Hospital and Health Service	Townsville
Australia	Ballarat Oncology and Haematology Clinical Trials Unit	Wendouree
Austria	Medical University of Graz	Graz
Austria	Medical University Innsbruck	Innsbruck	Tyrol
Austria	University Hospital St. Poelten	St. Poelten
Austria	Medical University Of Vienna	Vienna
Belgium	Cliniques Universitaires Saint-Luc	Brussels
Belgium	AZ Groeninge, Campus Kennedylaan	Kortrijk
Belgium	Clinique et Maternite Sainte-Elisabeth (CMSE)	Namur
Belgium	AZ Nikolaas	Sint Niklaas
Brazil	Fundacao Pio XII - Hospital de Amor de Barretos	Barretos
Brazil	Centro Avancado de Tratamento Oncologico (CENANTRON)	Belo Horizonte
Brazil	Liga Paranaense de Combate ao Cancer - Hospital Erasto Gaertner	Curitiba
Brazil	Oncosite Centro De Pesquisa Clinica Em Oncologia	Ijui
Brazil	Clinica de Neoplasias Litoral/atarina Pesquisa Clínica	Itajai
Brazil	Instituto Joinvilense De Hematologia E Oncologia	Joinville
Brazil	Animi Unidade de Tratamento Oncologico Ltda	Lages
Brazil	Hospital Bruno Born	Lajeado
Brazil	Hospital Sao Vicente de Paulo (HSVP) Instituto do Cancer	Passo Fundo
Brazil	CPO - Centro de Pesquisas em Oncologia	Porto Alegre
Brazil	Hospital de Clinicas de Porto Alegre (HCPA)	Porto Alegre
Brazil	Hospital Moinhos de Vento	Porto Alegre
Brazil	Fundacao PIO XII - Hospital de Amor Amazonia	Porto Velho
Brazil	Instituto COI	Rio de Janeiro
Brazil	Hospital Sao Rafael	Salvador
Brazil	INCA - Brazilian National Cancer Institute	Santo Cristo
Brazil	Fundacao Faculdade Regional de Medicina de Sao Jose do Rio Preto	Sao Jose do Rio Preto
Brazil	Hemomed	Sao paulo
Brazil	Hospital Sirio Libanes (HSL)	Sao Paulo
Brazil	Sao Camilo Oncologia	Sao Paulo
Canada	Royal Victoria Regional Health Centre	Barrie
Canada	Cross Cancer Institute (CCI)	Edmonton
Canada	Dr. Everett Chalmers Hospital	Fredericton
Canada	Saskatoon Cancer Centre (SCC)	Saskatoon
Canada	Sunnybrook Research Institute	Toronto	Ontario
Canada	University Health Network, Princess Margaret Cancer Centre	Toronto
Chile	Centro Oncologico Antofagasta Bradford Hill Norte	Antofagasta
Chile	Centro De Investigacion Clinica Bradford Hill	Recoleta	Chi
Chile	Hospital Clinico Universidad de Chile	Santiago
Chile	Oncovida	Santiago	Region Metropolitana De Santiago
Chile	Universidad Mayor - Centro Oncologia de Precision	Santiago
Chile	Oncocentro	Vina del Mar
Czechia	Fakultni Nemocnice Hradec Kralove	Hradec Kralove
Czechia	University Hospital Ostrava	Ostrava
Czechia	Fakultni nemocnice Kralovske Vinohrady, Dermatovenerologicka klinika	Prague 10
France	CHU Jean MINJOZ	Besancon Cedex
France	Hopital Avicenne Service de Dermatologie du Pr Caux	Bobigny
France	HOPITAL SAINT ANDRE Chu De Bordeaux	Bordeaux Cedex
France	Hopital Ambroise Pare	Boulogne Billancourt
France	CHU Estaing, Service de Dermatologie	Clermont-Ferrand
France	Hopitaux Universitaires Henri-Mondor	Creteil
France	CHU de DIJON - Service de Dermatologie	Dijon
France	Centre Hospitalier Universitaire De Grenoble Alpes Service Dermatologie	Grenoble
France	CH Le Mans - Plateforme de recherche clinique	Le Mans
France	Chru De Lille	Lille Cedex
France	Centre Leon Berard	Lyon cedex 08
France	Centre Hospitalier Universitaire de Nantes (CHU de Nantes) Hotel Dieu	Nantes
France	Hopital Cochin APHP	Paris
France	Hospices Civils de Lyon	Pierre Benite Cedex
France	Hopital de la Miletrie Centre Hospitalier Universitaire de Poitiers	Poitiers Cedex
France	CHU Charles Nicolle Dermatologie	Rouen
France	CHU Saint-Etienne - Hopital Nord	Saint-Etienne
France	Clinique Sainte Anne/Strasbourg Oncologie Liberale	Strasbourg
France	Institut Gustave Roussy Cancer Center DITEP	Villejuif Cedex
Georgia	LTD High Technology Hospital Medcenter	Batumi
Georgia	Israeli Georgian medical research clinic Helsicore	Tbilisi
Georgia	JSC K. Eristavi National Center of Experimental and Clinical Surgery	Tbilisi
Georgia	LLC Todua Clinic	Tbilisi
Georgia	LTD New Hospitals	Tbilisi
Georgia	LTD Tbilisi State Medical University and Ingorokva High Medical Technology University Clinic	Tbilisi
Georgia	Medulla - Clinics And Medical Centers	Tbilisi
Georgia	TIM -Tbilisi Institute of Medicine	Tbilisi
Germany	Universitatsklinikum Augsburg Klinik fur Dermatologie und Allergologie Campus Sud	Augsburg
Germany	Charite - Universitaetsmedizin Berlin	Berlin
Germany	Universitaetsklinikum der Ruhr Universitaet Bochum (UKRUB) St Josef Hospital	Bochum
Germany	Elbekliniken Buxtehude	Buxtehude
Germany	Staedtisches Klinikum Dessau	Dessau
Germany	Universitaetsklinikum Carl Gustav Carus an der Technischen Universitaet	Dresden
Germany	Helios Klinikum Erfurt Klinik fur Hautkrankheiten und Allergologie	Erfurt
Germany	Universitatsklinik Frankfurt	Frankfurt
Germany	University Hospital Giessen	Giessen
Germany	Universitatsmedizin Gottingen Klinik fur Dermatologie	Göttingen
Germany	University of Kiel	Kiel
Germany	Universitaetsklinikum Leipzig	Leipzig
Germany	Universitaetsklinikum Schleswig-Holstein Campus Luebeck	Luebeck
Germany	University Medical Center Mannheim	Mannheim
Germany	Fachklinik Hornheide	Muenster
Germany	Universitätsklinik der Paracelsus Medizinischen Privatuniversität	Nuremberg
Germany	Harzklinikum, Klinik fur Dermatologie und Allergologie	Quedlinburg
Germany	University Clinic Regensburg	Regensburg
Germany	Helios Klinik Schwerin	Schwerin
Germany	Universitaetsapotheke Tuebingen	Tuebingen
Hungary	University of Debrecen	Debrecen
Hungary	Szabolcs-Szatmar-Bereg Megyei Korhazak es Egyetemi Oktato Korhazak	Nyíregyhaza
Hungary	University of Pecs Medical School	Pecs
Hungary	University of Szeged	Szeged
Ireland	Cork University Hospital	Cork
Ireland	St. James Hospital	Dublin
Ireland	St. Vincents University Hospital	Dublin 4
Ireland	University College Hospital Galway	Galway
Italy	Istituto dei Tumori	Bari
Italy	ASST Spedali Civili Brescia	Brescia
Italy	Istituto di Candiolo, FPO IRCCS	Candiolo
Italy	Azienda Sanitaria Ospedaliera Santa Croce E Carle - Cuneo	Cuneo
Italy	Ospedale Policlinico San Martino - IRCCS	Genova
Italy	Fondazione IRCCS San Gerardo dei Tintori	Monza
Italy	IRCCS Istituto Nazionale dei Tumori di Napoli Fondazione G. Pascale	Napoli
Italy	Università della Campania Luigi Vanvitella	Napoli
Italy	SCDU di Oncologia AOU Maggiore Della Carita	Novara
Italy	IOV - Istituto Oncologico Veneto - IRCCS	Padova
Italy	U.O. Oncologia Medica Universitaria - Istituto Toscano Tumori Polo Oncologico	Pisa
Italy	Istituti Fisioterapici Ospitalieri (IFO)	Roma
Italy	Campus Bio-Medico di Roma	Rome
Italy	Istituto Dermopatico Dell'Immacolata Irccs	Rome
Italy	Fondazione IRCSS Casa Sollievo Della Sofferenza	San Giovanni Rotondo
Italy	Azienda Ospedaliera S. Maria	Terni
Italy	Santa Chiara Regional Hospital	Trento
Italy	AOU Citta della Salute e della Scienza di Torino	Turin
Italy	Azienda Sanitaria Universitaria Friuli Centrale (ASU FC) - Ospedale Udine	Udine
Mexico	Centro Estatal de Cancerologia de Chihuahua	Chihuahua
Mexico	Neurociencias Estudios Clinicos SC	Culiacan
Mexico	Antiguo Hospital Civil de Guadalajara Fray Antonio Alcalde	Guadalajara
Mexico	Preparaciones Oncologicas SC	Leon
Mexico	Centro De Atencion E Investigacion Clinica En Oncologia Scp	Merida
Mexico	iCan Oncology Center	Monterrey
Mexico	Centro De Estudios Y Prevencion Del Cancer A. C.	Tuxtla Gutierrez
Mexico	FAICIC S. de R.L. de C.V.	Veracruz
Mexico	Investigacion Biomedica para el Desarrollo de Farmacos S.A. de C.V.	Zapopan
Netherlands	The Netherlands Cancer Institute (NKI) - Antoni van Leeuwenhoek Hospital	Amsterdam
Netherlands	University Medical Center Groningen	Groningen
Peru	Centro Medico Monte Carmelo	Arequipa
Peru	Hospital Goyeneche	Arequipa
Peru	Hospital Nacional Daniel Alcides Carrion	Bellavista
Peru	Instituto Regional de Enfermedades Neoplasicas del Centro - IREN CENTRO	Concepcion
Peru	Instituto Nacional de Enfermedades Neoplasicas	Lima
Peru	Instituto Peruano de Oncologia and Radioterapia	Lima
Peru	Clinica Internacional San Borja	San Borja
Peru	Clinica Peruano Americana	Trujillo
Poland	Uniwersyteckie Centrum Kliniczne (UCK)	Gdansk
Poland	Narodowego Instytutu Onkologii im Maria Sklodowska Curie	Krakow
Poland	Uniwersytecki Szpital Kliniczny w Poznaniu	Poznan
Poland	Mazowiecki Szpital Wojewodzki, Siedleckie Centrum Onkologii	Siedlce
Poland	Wojewodzki Szpital Specjalistyczny im. Janusza Korczaka	Slupsk
Poland	Klinika Nowotworow Tkanek Miekkich, Kosci i Czerniakow	Warszawa
Romania	Institute of Oncology Bucharest	Bucharest
Romania	SC Radiotherapy Center Cluj SRL	Cluj
Romania	Medisprof	Cluj Napoca
Romania	Cardiomed SRL	Cluj-Napoca
Romania	Centrul de Oncologie Sf. Nectarie S.R.L	Craiova
Romania	Regional Institute of Oncology	Iasi
Romania	SC Centrul de Oncologie Euroclinic SRL	Iasi
Romania	RTC Radiology Therapeutic Center SRL	Otopeni
Romania	Oncocenter Oncologie Clinica S.R.L	Timisoara
Romania	Oncomed	Timisoara
South Africa	Groote Schuur Hospital	Cape Town
South Africa	The Medical Oncology Centre of Rosebank	Johannesburg
South Africa	Cape Town Oncology Trials	Kraaifontein
Spain	Hospital Teresa Herrera-Chuac (CHUAC)	A Coruna
Spain	Hospital Universitari Germans Trias i Pujol (HUGTP)	Badalona
Spain	Catalan Institute of Oncology (ICO) Hospitalet	Barcelona
Spain	Hospital de la Santa Creu i Sant Pau	Barcelona
Spain	Instituto Oncologico Dr Rosel	Barcelona
Spain	Hospital Universitario Reina Sofia	Cordoba
Spain	Catalan Institute Of Oncology - Girona	Girona
Spain	Hospital Universitario Virgen de las Nieves	Granada
Spain	Hospital Universitario Lucus Augusti	Lugo
Spain	Centro integral Oncologico HM Clara Campal	Madrid
Spain	Hospital Fundacion Jimenez Diaz	Madrid
Spain	Hospital General Universitario Gregorio Maranon	Madrid
Spain	Hospital Universitario La Paz	Madrid
Spain	Hospital Universitario Ramon y Cajal	Madrid
Spain	Hospital Regional Universitario de Malaga	Malaga
Spain	Hospital Universitario Virgen de la Arrixaca	Múrcia
Spain	Hospital Universitario Central de Asturias	Oviedo
Spain	Onkologikoa	San Sebastian
Spain	Hospital Universitario Virgen Macarena	Sevilla
Spain	INCLIVA-Instituto de Investigacion Sanitaria	Valencia
Spain	Instituto Valenciano de Oncologia	Valencia
Turkey	Adana Baskent Hospital	Adana
Turkey	Gulhane Training and Research Hospital	Ankara
Turkey	Memorial Ankara Hospital	Ankara
Turkey	Ozel Liv Hospital	Ankara
Turkey	Dicle University Medical Faculty	Diyarbakir
Turkey	Trakya University	Edirne
Turkey	Gaziantep University Medical Faculty	Gaziantep
Turkey	Bakirkoy Sadi Konuk Training Hospital	Istanbul
Turkey	Bezmialem University	Istanbul
Turkey	Cerrahpasa Medical Hospital	Istanbul
Turkey	Prof. Dr. Suleyman Yalcin Sehir Hospital	Istanbul
Turkey	Ege University hospital	Izmir
Turkey	Kocaeli Universitesi	Kocaeli
United Kingdom	Royal Devon and Exeter Hospital NHS Trust	Exeter	Devon
United Kingdom	Royal Surrey NHS Foundation Trust	Guildford
United Kingdom	Hull University Teaching Hospitals NHS Trust	Hull
United Kingdom	Leeds Teaching Hospitals NHS Trust	Leeds
United Kingdom	Guy's Hospital	London
United States	Cleveland Clinic Foundation	Cleveland	Ohio
United States	University Hospitals Seidmand Cancer Center	Cleveland	Ohio
United States	University of Tennessee Medical Center	Knoxville	Tennessee
United States	University of California San Diego	La Jolla	California
United States	The Angeles Clinic and Research Institute	Los Angeles	California
United States	Miami Cancer Institute	Miami	Florida
United States	Atlantic Health System - Morristown Medical Center	Morristown	New Jersey
United States	Orlando Health, Inc	Orlando	Florida

Sponsors (1)

Lead Sponsor	Collaborator
Regeneron Pharmaceuticals

Countries where clinical trial is conducted

United States,  Argentina,  Australia,  Austria,  Belgium,  Brazil,  Canada,  Chile,  Czechia,  France,  Georgia,  Germany,  Hungary,  Ireland,  Italy,  Mexico,  Netherlands,  Peru,  Poland,  Romania,  South Africa,  Spain,  Turkey,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Progression-free survival (PFS)	Per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 based on Blinded Independent Central Review (BICR)	Approximately 27 months
Secondary	Overall survival (OS)		Up to 96 months
Secondary	Objective response rate (ORR)	Per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 based on Blinded Independent Central Review (BICR) or based on investigator assessment according to RECIST 1.1 and immune RECIST (iRECIST)	Up to 27 months
Secondary	Disease control rate (DCR)	Per RECIST 1.1 based on BICR or based on investigator assessment according to RECIST 1.1 and immune RECIST (iRECIST)	Up to 27 months
Secondary	Duration of response (DoR)	Per RECIST 1.1 via BICR or based on investigator assessment according to RECIST 1.1 and immune RECIST (iRECIST)	Up to 27 months
Secondary	PFS	Based on investigator assessment according to RECIST 1.1 and immune RECIST (iRECIST)	Up to 27 months
Secondary	Incidence of Adverse Events (AEs)	Including treatment emergent adverse events (TEAEs), serious adverse events (SAEs), adverse events of special interest (AESIs), and/ or immune-related adverse event (irAEs)	Up to 90 days post last dose, approximately 6 years
Secondary	Occurrence of interruption and discontinuation of study drug(s) due to AEs	Including TEAEs, AESIs, and/ or irAEs	Up to 90 days post last dose, approximately 6 years
Secondary	Incidence of deaths		Up to 6 years
Secondary	Incidence of laboratory abnormalities	Will be graded using the current version of the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) grading system (version 5.0)	Up to 90 days post last dose, approximately 6 years
Secondary	Concentrations of cemiplimab in serum		Up to 90 days post last dose, approximately 6 years
Secondary	Concentrations of fianlimab in serum		Up to 90 days post last dose, approximately 6 years
Secondary	Incidence of anti-drug antibodies (ADA) to fianlimab over time		Up to 30 days post last dose, approximately 6 years
Secondary	Titer of anti-drug antibodies (ADA) to fianlimab over time		Up to 30 days post last dose, approximately 6 years
Secondary	Incidence of ADA to cemiplimab over time		Up to 30 days post last dose, approximately 6 years
Secondary	Titer of ADA to cemiplimab over time		Up to 30 days post last dose, approximately 6 years
Secondary	Incidence of neutralizing antibodies (NAb) to fianlimab over time		Up to 30 days post last dose, approximately 6 years
Secondary	Incidence of NAb to cemiplimab over time		Up to 30 days post last dose, approximately 6 years
Secondary	Patient-reported outcomes (PROs) as measured by European Organization for Research and Treatment of Cancer Quality of Life Questionnaire C30 (EORTC QLQ-C30)	EORTC-QLQ-C30 is a 30-item participant self-report questionnaire composed of both multi-item and single scales, including a global health status/quality of life (GHS/QoL) scale. Participants rate items on a four-point scale, with 1 as "not at all" and 4 as "very much." A change of 5 - 10 points is considered a small change. A change of 10 - 20 points is considered a moderate change.	Up to 90 days post last dose, approximately 6 years
Secondary	PROs as measured by EQ-5D-5L	The EQ-5D-5L consists of EQ-5D descriptive system comprises five dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each dimension has 5 levels: no problems, slight problems, moderate problems, severe problems and extreme problems. Overall scores range from 0 to 1, with low scores representing a higher level of dysfunction.	Up to 90 days post last dose, approximately 6 years
Secondary	PROs as measured by Functional Assessment of Cancer Therapy melanoma (FACTM) (melanoma subscale only)	The FACTM is a melanoma-specific quality of life questionnaire that is composed of items from the Functional Assessment of Cancer Therapy-General (FACT-G). The FACTM is scored on a 5 point Likert-scale: "Not at all", "A little bit", "Somewhat", "Quite a bit", and "Very much.". A Higher score represents higher Health Related Quality of Life (HRQoL).	Up to 90 days post last dose, approximately 6 years
Secondary	PROs as measured by Patient Global Impression of Severity (PGIS)	The PGIS is a single 1-item questionnaire designed to assess participant's overall impression of disease severity at a given point in time by using a 4-point Likert scale that ranges from (1) = "none (no symptoms)" to (4) = "severe".	Up to 21 days post last dose, approximately 6 years
Secondary	PROs as measured by Patient Global Impression of Change (PGIC)	The PGIC is a single-item questionnaire designed to assess the participant's overall sense of whether there has been a change since starting treatment as rated on a 5-point Likert scale anchored by (1) "much better" to (5) "much worse", with (4) = "no change"	Up to 21 days post last dose, approximately 6 years
Secondary	Change in physical functioning per EORTC QLQ-C30	EORTC-QLQ-C30 is a 30-item subject self-report questionnaire composed of both multi-item and single scales, including a global health status/quality of life (GHS/QoL) scale. Participants rate items on a four-point scale, with 1 as "not at all" and 4 as "very much." A change of 5 - 10 points is considered a small change. A change of 10 - 20 points is considered a moderate change.	Baseline to Week 25
Secondary	Change in role functioning per EORTC QLQ-C30	EORTC-QLQ-C30 is a 30-item subject self-report questionnaire composed of both multi-item and single scales, including a global health status/quality of life (GHS/QoL) scale. Participants rate items on a four-point scale, with 1 as "not at all" and 4 as "very much." A change of 5 - 10 points is considered a small change. A change of 10 - 20 points is considered a moderate change.	Baseline to Week 25
Secondary	Change in global health status/quality of life (GHS/QoL) per EORTC QLQ-C30	Global Health Status/Quality of Life (GHS/Qol) Score (Items 29 and 30) using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30). Participants rate items on a four-point scale, with 1 as "not at all" and 4 as "very much." A change of 5 - 10 points is considered a small change. A change of 10 - 20 points is considered a moderate change.	Baseline to Week 25
Secondary	Change in physical functioning per EORTC QLQ-C30	EORTC-QLQ-C30 is a 30-item subject self-report questionnaire composed of both multi-item and single scales, including a global health status/quality of life (GHS/QoL) scale. Participants rate items on a four-point scale, with 1 as "not at all" and 4 as "very much." A change of 5 - 10 points is considered a small change. A change of 10 - 20 points is considered a moderate change.	Baseline to end of study, approximately 6 years
Secondary	Change in role functioning per EORTC QLQ-C30	EORTC-QLQ-C30 is a 30-item subject self-report questionnaire composed of both multi-item and single scales, including a global health status/quality of life (GHS/QoL) scale. Participants rate items on a four-point scale, with 1 as "not at all" and 4 as "very much." A change of 5 - 10 points is considered a small change. A change of 10 - 20 points is considered a moderate change.	Baseline to end of study, approximately 6 years
Secondary	Change in GHS/QoL per EORTC QLQ-C30	EORTC-QLQ-C30 is a 30-item subject self-report questionnaire composed of both multi-item and single scales, including a global health status/quality of life (GHS/QoL) scale. Participants rate items on a four-point scale, with 1 as "not at all" and 4 as "very much." A change of 5 - 10 points is considered a small change. A change of 10 - 20 points is considered a moderate change.	Baseline to end of study, approximately 6 years

External Links

•   A clinical study for adults and adolescents with advanced melanoma skin cancer.