Clinical trial NCT05155254: IO102-IO103 in Combination With Pembrolizumab Versus Pembrolizumab Alone in Advanced Melanoma (IOB-013 / KN-D18)
Official title: An Open-label, Randomized, Phase 3 Clinical Trial of IO102-IO103 in Combination With Pembrolizumab Versus Pembrolizumab Alone in Patients With Previously Untreated, Unresectable, or Metastatic (Advanced) Melanoma (IO102-IO103-013 / MK3475-D18)
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE3
Conditions: Metastatic Melanoma
Unresectable Melanoma
Keywords: Metastatic melanoma
Unresectable melanoma
Immunotherapy
Progression free survival
IO102-IO103
Pembrolizumab
Lead sponsor: IO Biotech
Sponsor class: INDUSTRY
Collaborators: name: Syneos Health
name: Merck Sharp & Dohme LLC
First posted: 2021-12-13
Enrollment: 407
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Patients will be randomised 1:1 to receive either dual-antigen IO102-IO103 in combination with pembrolizumab versus pembrolizumab alone
Primary purpose: TREATMENT

Brief summary: Phase 3, multicenter, international, open-label, randomized, 2-arm trial investigating the safety and efficacy of IO102-IO103 in combination with pembrolizumab as first-line treatment for patients with previously untreated unresectable or metastatic (advanced) melanoma.

Patients will be stratified on the basis of the following factors; Disease stage: Stage III (unresectable) and IV M1a-b versus stage IV M1c-d and BRAFV600 mutation status: mutated vs wild type.

All patients will receive pembrolizumab 200 mg intravenously every 3 weeks for a maximum of 35 cycles (up to 2 years treatment). Patients randomized to IO102-IO103 dual-antigen, immunotherapeutic arm will also be given IO102-IO103 Q3W with an additional dose given during the induction period on Day 8 of cycles 1 and 2. IO102 IO103 will thereafter be administered subcutaneous every 3 weeks during the maintenance period. Each patient can be treated for a maximum of 37 administrations in total (up to 2 years of treatment).

The primary objective is to investigate the efficacy of IO102-IO103 in combination with pembrolizumab (compared with pembrolizumab alone) in terms of progression free survival.


Eligibility criteria: Inclusion Criteria:

1. Histologically or cytologically confirmed stage III (unresectable) or stage IV melanoma, as per American Joint Committee on Cancer 8th edition guidelines not amenable to local therapy
2. Patients are treatment naive, that is, no previous systemic anticancer therapy for unresectable or metastatic melanoma. For clarification, the following patients are eligible:

   1. Patients with BRAFV600 mutation-positive melanoma are eligible if treatment naive and without rapidly progressive disease as per investigators assessment. Documented BRAF V600 mutation status must be available from all patients prior to trial entry.
   2. Patients who have received previous adjuvant and/or neoadjuvant therapy with targeted therapy or immune therapy are eligible if administered the last dose at least 6 months before inclusion in this trial (randomization), and if relapse did not occur during active treatment or within 6 months of treatment discontinuation.
3. At least 1 measurable lesion according to response evaluation criteria for solid tumors (RECIST v1.1) and confirmed by IRC.
4. Provision of archival (obtained within 3 months), or newly acquired biopsy tissue not previously irradiated, and blood at screening for biomarker assessments. Formalin-fixed, paraffin embedded (FFPE) tissue blocks are preferred to slides. Newly obtained biopsies are preferred to archived tissue.

Exclusion Criteria:

1. Patients with known or suspected central nervous system (CNS) metastases or with the CNS as the only site of active disease are excluded with the following exception:

   • Patients with controlled (stable) brain metastases will be allowed to enroll (subject to baseline magnetic resonance imaging (MRI) confirmation). Controlled (stable) brain metastases are defined as those with no radiographic progression for at least 4 weeks after radiation and/or surgical treatment at the time of signed informed consent. Patients must have been off steroids for at least 2 weeks before signed informed consent and have no new or progressive neurological signs and symptoms.
2. Patient has received previous radiotherapy within 2 weeks of start of trial treatment (visit 2). Patients must have recovered from all radiation-related toxicities, not require corticosteroids, and not have had radiation pneumonitis. A 1-week washout is permitted for palliative radiation (≤2 weeks of radiotherapy) to non-CNS disease.
3. Patients with BRAFV600-positive disease who are experiencing rapidly progressing disease and/or have received standard first-line therapy with BRAF and/or MEK inhibitor for unresectable or metastatic disease.

Other protocol defined inclusion/exclusion criteria may apply.

Primary outcomes:
measure: Progression Free Survival (PFS)
timeFrame: Approximately 3.5 years
Secondary outcomes:
measure: Overall Response Rate (ORR)
timeFrame: Approximately 2.5 years
measure: Overall survival (OS)
timeFrame: Approximately 5.5 years
measure: Durable Objective response rate (DRR)
timeFrame: Approximately 3.5 years
measure: Complete response rate (CRR)
timeFrame: Approximately 3.5 years
measure: Duration of response (DoR)
timeFrame: Approximately 3.5 years
measure: Time to response (TTR)
timeFrame: Approximately 3.5 years
measure: Time to complete response (TTCR)
timeFrame: Approximately 3.5 years
measure: Disease control rate (DCR)
timeFrame: Approximately 3.5 years
measure: Incidence of e.g. AEs and SAEs (Safety and Tolerability)
timeFrame: Approximately 3.5 years
Other outcomes:
Locations:
city: Orange City
country: United States
facility: Mid Florida Hematology and Oncology Center
state: Florida
city: Orlando
country: United States
facility: Orlando Health Cancer Institute
state: Florida
city: Buffalo
country: United States
facility: Roswell Park Cancer Institute
state: New York
city: Richmond
country: United States
facility: VCU Massey Cancer Center
state: Virginia
city: Albury
country: Australia
facility: Border Medical Oncology Research Unit
state: New South Wales
city: Westmead
country: Australia
facility: Westmead Hospital
state: New South Wales
city: Wollongong
country: Australia
facility: Southern Medical Day Care Centre
state: New South Wales
city: Cairns
country: Australia
facility: Cairns Hospital
state: Queensland
city: Bedford Park
country: Australia
facility: Flinders Medical Centre
state: South Australia
city: Woodville South
country: Australia
facility: The Queen Elizabeth Hospital
state: South Australia
city: Birtinya
country: Australia
facility: Sunshine Coast University Hospital
city: Melbourne
country: Australia
facility: Peter MacCallum Cancer Centre PMCC - East Melbourne
city: Gent
country: Belgium
facility: Universitair Ziekenhuis Gent UZ Gent
state: Oost-Vlaanderen
city: Sint-Niklaas
country: Belgium
facility: AZ Nikolaas
city: Hradec Králové
country: Czechia
facility: FNHK Klinika onkologie a radioterapie
city: Olomouc
country: Czechia
facility: Fakultni Nemocnice Olomouc
city: Ostrava
country: Czechia
facility: FN Ostrava
city: Praha
country: Czechia
facility: FNKV Department of Dermatology
city: Aalborg
country: Denmark
facility: Aalborg University Hospital
city: Aarhus
country: Denmark
facility: Aarhus University Hospital
city: Herlev
country: Denmark
facility: Herlev og Gentofte Hospital
city: Odense
country: Denmark
facility: Odense University Hospital
city: Besancon
country: France
facility: Centre Hospitalier Universitaire de Besançon Jean Minjoz
city: Bordeaux
country: France
facility: Centre Hospitalier Universitaire de Bordeaux Hospital Saint Andre
city: Boulogne Billancourt
country: France
facility: Hopital Ambroise
city: Dijon
country: France
facility: Centre Georges Francois Leclerc
city: La Tronche
country: France
facility: Chu Grenoble - Hopital Albert Michallon
city: Lille
country: France
facility: Centre Hospitalier Universitaire de Lille
city: Marseille cedex 05
country: France
facility: Hôpital de La Timone
city: Nice
country: France
facility: CHU de Nice Hpital de lArchet 2
city: Pierre Benite
country: France
facility: Centre Hospitalier Lyon Sud
city: Rennes Cedex
country: France
facility: Centre Eugene Marquis
city: Saint Herblain
country: France
facility: Institut de Cancérologie de L'Ouest
city: Valence
country: France
facility: Centre Hospitalier de Valence (CHV)
city: Villejuif Cedex
country: France
facility: Gustave Roussy
city: Augsburg
country: Germany
facility: Universitatsklinikum Augsburg Medizincampus Sued
city: Berlin
country: Germany
facility: Charite Universitaetsmedizin Berlin
city: Bochum
country: Germany
facility: St. Josef Hospital - Ruhr-Universitt Bochum
city: Erlangen
country: Germany
facility: University Hospital Erlangen
city: Essen
country: Germany
facility: Universitaetsklinikum Essen
city: Frankfurt
country: Germany
facility: University Hospital Frankfurt Theodor-Stern-Kai
city: Halle (Saale)
country: Germany
facility: Universitatsklinik fur Dermatologie und Venerologie der MLU Halle-Wittenberg
city: Hamburg
country: Germany
facility: Elbe Klinikum Buxtehude
city: Heidelberg
country: Germany
facility: Nationales Centrum fr Tumorerkrankungen NCT
city: Heilbronn
country: Germany
facility: SLK-Kliniken Heilbronn GmbH
city: Kiel
country: Germany
facility: Universitaetsklinikum Schleswig-Holstein
city: Mainz
country: Germany
facility: Department of Dermatology University of Mainz
city: Mannheim
country: Germany
facility: Universitatsmedizin Mannheim Dermatologie
city: Minden
country: Germany
facility: Mühlenkreiskliniken AöR, University Hospital Ruhr University Bochum Campus Minden
city: Muenchen
country: Germany
facility: LMU Muenchen
city: Münster
country: Germany
facility: Universitaetsklinikum Muenster
city: Tubingen
country: Germany
facility: Hospital Tubingen
city: Wuerzburg
country: Germany
facility: Universittsklinikum Wuerzburg
city: Budapest
country: Hungary
facility: Orszagos Onkologiai Intezet
city: Pecs
country: Hungary
facility: Bor, -Nemikortani es Onkodermatologiai Klinika
city: Szolnok
country: Hungary
facility: Hetenyi G Korhaz, Onkologiai Kozpont
city: Afula
country: Israel
facility: Emek Medical Center
city: Beer Sheva
country: Israel
facility: Ben-Gurion University of the Negev - Soroka University Medical Center - Soroka Clinical Research Center
city: Jerusalem
country: Israel
facility: Hadassah University Hospital
city: Petah Tikva
country: Israel
facility: Rabin Medical Center
city: Tel Aviv-Yafo
country: Israel
facility: Tel Aviv Sourasky Medical Center
city: Tel Hashomer
country: Israel
facility: The Chaim Sheba Medical Center - The Ella Lemelbaum Institute for Immuno-Oncology
city: Ancona
country: Italy
facility: Clinica Oncologica, AOU Riuniti ancona
city: Aviano
country: Italy
facility: Centro di Riferimento Oncologico
city: Bari
country: Italy
facility: Istituto Tumori Giovanni Paolo II IRCCS Ospedale Oncologico Bari
city: Candiolo
country: Italy
facility: IRCCS Ospedale San Raffaele
city: Genova
country: Italy
facility: IRCCS Ospedale Policlinico San Martino
city: Meldola
country: Italy
facility: Istituto Romagnolo per lo Studio dei Tumori " DINO AMADORI"
city: Milano
country: Italy
facility: Fondazione IRCCS Istituto Nazionale dei Tumori
city: Napoli
country: Italy
facility: Istituto Nazionale Tumori IRCCS Fondazione Pascale
city: Padova
country: Italy
facility: Veneto Oncology Institute
city: Perugia
country: Italy
facility: Ospedale S. Maria della Misericordia
city: Roma
country: Italy
facility: IRCCS Istituti Fisioterapici Ospitalieri
city: Rome
country: Italy
facility: Idi-Irccs
city: Siena
country: Italy
facility: Azienda Ospedaliera Universitaria Senese Policlinico Le Scotte
city: Amsterdam
country: Netherlands
facility: The Netherlands Cancer Institute
city: Amsterdam
country: Netherlands
facility: AMC Amsterdam, locatie VUMC
city: Leiden
country: Netherlands
facility: LUMC
city: Maastricht
country: Netherlands
facility: UMC Maastricht
city: Rotterdam
country: Netherlands
facility: Erasmus MC
city: Utrecht
country: Netherlands
facility: University Medical Center Utrecht
city: Warsaw
country: Poland
facility: Maria Sklodowska-Curie National Research Institute of Oncology
state: Masovian
city: Poznan
country: Poland
facility: Szpital Kliniczny im. Heliodora Święcickiego UM w Poznaniu
city: Cape Town
country: South Africa
facility: Cape Town Oncology Trials (Pty) Ltd.
city: Pretoria
country: South Africa
facility: Mary Potter Oncology Centre Groenkloof
city: Seville
country: Spain
facility: Hospital Universitario Virgen Macarena
state: Andalusia
city: A Coruña
country: Spain
facility: CH Universitario de A Coruña (CHUAC)
city: Barcelona
country: Spain
facility: Hospital Clinic i Provincial
city: Barcelona
country: Spain
facility: Instituto Oncologico Dr. Rosell IOR - Hospital Universitari Quiron Dexeus
city: Barcelona
country: Spain
facility: Hospital Universitari Germans Trias i Pujol HUGTP, ICO-Badalona
city: Barcelona
country: Spain
facility: Hospital Vall d'hebron
city: Madrid
country: Spain
facility: Hospital General Universitario Gregorio MaraÃ±on
city: Madrid
country: Spain
facility: Clinica Universidad de Navarra
city: Madrid
country: Spain
facility: Hospital Universitario Ramon y Cajal
city: Madrid
country: Spain
facility: Hospital Universitario HM Sanchinarro
city: Malaga
country: Spain
facility: Hospital Regional Universitario de Malaga
city: Oviedo
country: Spain
facility: Hospital Universitario Central de Asturias (HUCA)
city: Pamplona
country: Spain
facility: Clinica Universidad de Navarra
city: Valencia
country: Spain
facility: Hospital General Universitario de Valencia
city: Valencia
country: Spain
facility: Hospital Universitari i Politecnic La Fe
city: Zaragoza
country: Spain
facility: Miguel Servet University Hospital
city: Adana
country: Turkey
facility: Adana City Education and Research Hospital
city: Ankara
country: Turkey
facility: Gulhane School of Medicine
city: Ankara
country: Turkey
facility: Memorial Ankara Hospital
city: Antalya
country: Turkey
facility: Akdeniz University Medical Faculty
city: Bornova
country: Turkey
facility: Ege university Faculty of Medicine, T. Aktas Oncology Hospital, Bornova
city: Istanbul
country: Turkey
facility: Istanbul University-Cerrahpasa, Cerrahpasa Medical Faculty
city: Istanbul
country: Turkey
facility: Goztepe Prof. Dr. Suleyman Yalcin Sehir Hastanesi
city: London
country: United Kingdom
facility: Guy's Hospital
city: Manchester
country: United Kingdom
facility: Christie Hospital NHS Trust
city: Manchester
country: United Kingdom
facility: Christie Hospital NHS Trust
city: Oxford
country: United Kingdom
facility: Oxford University Hospitals NHS Foundation Trust
Study officials:
affiliation: Institut for Klinisk Medicin, Herlev-Gentofte Hospital; Denmark
name: Inge Marie Svane, MD, Prof
role: PRINCIPAL_INVESTIGATOR
References: