IO102-IO103 in Combination With Pembrolizumab Versus Pembrolizumab Alone in Advanced Melanoma (IOB-013 / KN-D18)

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)

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.

Study Overview

• Status: Active, not recruiting
• Conditions: Metastatic Melanoma; Unresectable Melanoma
• Intervention / Treatment: Drug: IO102-IO103; Drug: Pembrolizumab

• Study Type: Interventional
• Enrollment (Actual): 407
• Phase: Phase 3

Contacts and Locations

Study Locations

• Australia
  • Birtinya, Australia, 4575
    • Sunshine Coast University Hospital
  • Melbourne, Australia, 3052
    • Peter MacCallum Cancer Centre PMCC - East Melbourne
  • New South Wales
    • Albury, New South Wales, Australia, 2640
      • Border Medical Oncology Research Unit
    • Westmead, New South Wales, Australia, 2145
      • Westmead Hospital
    • Wollongong, New South Wales, Australia, 2500
      • Southern Medical Day Care Centre
  • Queensland
    • Cairns, Queensland, Australia, 4870
      • Cairns Hospital
  • South Australia
    • Bedford Park, South Australia, Australia, 5042
      • Flinders Medical Centre
    • Woodville South, South Australia, Australia, 5011
      • The Queen Elizabeth Hospital
• Belgium
  • Sint-Niklaas, Belgium, 9100
    • AZ Nikolaas
  • Oost-Vlaanderen
    • Ghent, Oost-Vlaanderen, Belgium, 9000
      • Universitair Ziekenhuis Gent UZ Gent
• Czechia
  • Hradec Králové, Czechia, 500 05
    • FNHK Klinika onkologie a radioterapie
  • Olomouc, Czechia, 779 00
    • Fakultni nemocnice Olomouc
  • Ostrava, Czechia, 708 52
    • FN Ostrava
  • Prague, Czechia, 10034
    • FNKV Department of Dermatology
• Denmark
  • Aalborg, Denmark, 9000
    • Aalborg University Hospital
  • Aarhus, Denmark, 8200
    • Aarhus University Hospital
  • Herlev, Denmark, 2730
    • Herlev og Gentofte Hospital
  • Odense, Denmark, 5000
    • Odense University Hospital
• France
  • Besançon, France, 25000
    • Centre Hospitalier Universitaire de Besançon Jean Minjoz
  • Bordeaux, France, 33075
    • Centre Hospitalier Universitaire de Bordeaux Hospital Saint Andre
  • Boulogne-Billancourt, France, 92100
    • Hopital Ambroise
  • Dijon, France, 21079
    • Centre Georges Francois Leclerc
  • La Tronche, France, 38700
    • Chu Grenoble - Hopital Albert Michallon
  • Lille, France, 59000
    • Centre Hospitalier Universitaire De Lille
  • Marseille, France, 13385
    • Hopital de la Timone
  • Nice, France, 6200
    • CHU de Nice Hpital de lArchet 2
  • Pierre-Bénite, France, 69495
    • Centre Hospitalier Lyon Sud
  • Rennes, France, 35042
    • Centre Eugene Marquis
  • Saint-Herblain, France, 44805
    • Institut de cancerologie de l'ouest
  • Valence, France, 26 953
    • Centre Hospitalier de Valence (CHV)
  • Villejuif, France, 94805
    • Gustave Roussy
• Germany
  • Augsburg, Germany, 86179
    • Universitatsklinikum Augsburg Medizincampus Sued
  • Berlin, Germany, 13353
    • Charite Universitaetsmedizin Berlin
  • Bochum, Germany, 44791
    • St. Josef Hospital - Ruhr-Universitt Bochum
  • Erlangen, Germany, 90054
    • University Hospital Erlangen
  • Essen, Germany, 45147
    • Universitaetsklinikum Essen
  • Frankfurt, Germany, 60590
    • University Hospital Frankfurt Theodor-Stern-Kai
  • Halle, Germany, 6120
    • Universitatsklinik fur Dermatologie und Venerologie der MLU Halle-Wittenberg
  • Hamburg, Germany, 22045
    • Elbe Klinikum Buxtehude
  • Heidelberg, Germany, 69120
    • Nationales Centrum fr Tumorerkrankungen NCT
  • Heilbronn, Germany, 74078
    • SLK-Kliniken Heilbronn GmbH
  • Kiel, Germany, 24105
    • Universitaetsklinikum Schleswig-Holstein
  • Mainz, Germany, 55131
    • Department of Dermatology University of Mainz
  • Mannheim, Germany, 68167
    • Universitatsmedizin Mannheim Dermatologie
  • Minden, Germany, 32429
    • Mühlenkreiskliniken AöR, University Hospital Ruhr University Bochum Campus Minden
  • München, Germany, 80337
    • LMU Muenchen
  • Münster, Germany, 48149
    • Universitaetsklinikum Muenster
  • Tübingen, Germany, 72076
    • Hospital Tubingen
  • Würzburg, Germany, 97080
    • Universittsklinikum Wuerzburg
• Hungary
  • Budapest, Hungary, 1122
    • Orszagos Onkologiai Intezet
  • Pécs, Hungary, 7632
    • Bor, -Nemikortani es Onkodermatologiai Klinika
  • Szolnok, Hungary, 5000
    • Hetenyi G Korhaz, Onkologiai Kozpont
• Israel
  • Afula, Israel
    • Emek Medical Center
  • Beersheba, Israel, 84101
    • Ben-Gurion University of the Negev - Soroka University Medical Center - Soroka Clinical Research Center
  • Jerusalem, Israel, 91120
    • Hadassah University Hospital
  • Petah Tikva, Israel, 4941492
    • Rabin Medical Center
  • Tel Aviv, Israel
    • Tel Aviv Sourasky Medical Center
  • Tel Litwinsky, Israel, 5262100
    • The Chaim Sheba Medical Center - The Ella Lemelbaum Institute for Immuno-Oncology
• Italy
  • Ancona, Italy, 60126
    • Clinica Oncologica, AOU Riuniti ancona
  • Aviano, Italy, 33081
    • Centro Di Riferimento Oncologico
  • Bari, Italy, 70124
    • Istituto Tumori Giovanni Paolo Ii Irccs Ospedale Oncologico Bari
  • Candiolo, Italy, 10060
    • IRCCS Ospedale San Raffaele
  • Genova, Italy, 16132
    • IRCCS Ospedale Policlinico San Martino
  • Meldola, Italy, 47014
    • Istituto Romagnolo per lo Studio dei Tumori " DINO AMADORI"
  • Milan, Italy, 20133
    • Fondazione IRCCS Istituto Nazionale dei Tumori
  • Napoli, Italy, 80131
    • Istituto Nazionale Tumori IRCCS Fondazione Pascale
  • Padua, Italy, 35128
    • Veneto Oncology Institute
  • Perugia, Italy, 6156
    • Ospedale S. Maria Della Misericordia
  • Roma, Italy, 144
    • IRCCS Istituti Fisioterapici Ospitalieri
  • Rome, Italy, 00167
    • Idi-Irccs
  • Siena, Italy, 53100
    • Azienda Ospedaliera Universitaria Senese Policlinico Le Scotte
• Netherlands
  • Amsterdam, Netherlands, 1066
    • The Netherlands Cancer Institute
  • Amsterdam, Netherlands, 1081
    • AMC Amsterdam, locatie VUMC
  • Leiden, Netherlands, 2300 RC
    • LUMC
  • Maastricht, Netherlands, 6229HX
    • UMC Maastricht
  • Rotterdam, Netherlands, 1054 ZG
    • Erasmus MC
  • Utrecht, Netherlands, 3584
    • University Medical Center Utrecht
• Poland
  • Poznan, Poland, 60-780
    • Szpital Kliniczny im. Heliodora Święcickiego UM w Poznaniu
  • Masovian Voivodeship
    • Warsaw, Masovian Voivodeship, Poland, 02-781
      • Maria Sklodowska-Curie National Research Institute of Oncology
• South Africa
  • Cape Town, South Africa, 7570
    • Cape Town Oncology Trials (Pty) Ltd.
  • Pretoria, South Africa, 0181
    • Mary Potter Oncology Centre Groenkloof
• Spain
  • A Coruña, Spain, 15006
    • CH Universitario de A Coruña (CHUAC)
  • Barcelona, Spain, 08036
    • Hospital Clínic i Provincial
  • Barcelona, Spain
    • Hospital Vall d'Hebron
  • Barcelona, Spain, 8028
    • Instituto Oncologico Dr. Rosell IOR - Hospital Universitari Quiron Dexeus
  • Barcelona, Spain, 8916
    • Hospital Universitari Germans Trias i Pujol HUGTP, ICO-Badalona
  • Madrid, Spain, 28034
    • Hospital Universitario Ramon y Cajal
  • Madrid, Spain, 28027
    • Clinica Universidad de Navarra
  • Madrid, Spain, 28050
    • Hospital Universitario HM Sanchinarro
  • Madrid, Spain, 28007
    • Hospital General Universitario Gregorio Marañon
  • Málaga, Spain, 29010
    • Hospital Regional Universitario de Malaga
  • Oviedo, Spain, 33011
    • Hospital Universitario Central de Asturias (HUCA)
  • Pamplona, Spain, 31008
    • Clinica Universidad de Navarra
  • Valencia, Spain, 46026
    • Hospital Universitari i Politecnic La Fe
  • Valencia, Spain, 46014
    • Hospital General Universitario de Valencia
  • Zaragoza, Spain, 50009
    • Miguel Servet University Hospital
  • Andalusia
    • Seville, Andalusia, Spain, 41009
      • Hospital Universitario Virgen Macarena
• Turkey (Türkiye)
  • Adana, Turkey (Türkiye), 1060
    • Adana City Education and Research Hospital
  • Ankara, Turkey (Türkiye), 6010
    • Gulhane School of Medicine
  • Ankara, Turkey (Türkiye), 6520
    • Memorial Ankara Hospital
  • Antalya, Turkey (Türkiye), 7059
    • Akdeniz University Medical Faculty
  • Bornova, Turkey (Türkiye), 35100
    • Ege university Faculty of Medicine, T. Aktas Oncology Hospital, Bornova
  • Istanbul, Turkey (Türkiye), 34098
    • Istanbul University-Cerrahpasa, Cerrahpasa Medical Faculty
  • Istanbul, Turkey (Türkiye), 34722
    • Goztepe Prof. Dr. Suleyman Yalcin Sehir Hastanesi
• United Kingdom
  • London, United Kingdom, SE1 9RT
    • Guy's Hospital
  • Manchester, United Kingdom, M20 4BX
    • Christie Hospital NHS Trust
  • Manchester, United Kingdom, M20 4XB
    • Christie Hospital NHS Trust
  • Oxford, United Kingdom, OX3 7LE
    • Oxford University Hospitals NHS Foundation Trust
• United States
  • Florida
    • Orange City, Florida, United States, 32763
      • Mid Florida Hematology and Oncology Center
    • Orlando, Florida, United States, 32806
      • Orlando Health Cancer Institute
  • New York
    • Buffalo, New York, United States, 14221
      • Roswell Park Cancer Institute
  • Virginia
    • Richmond, Virginia, United States, 23219
      • Vcu Massey Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: IO102-IO103 + pembrolizumab; IO102-IO103 subcutaneous injections (85µg) every 3 weeks for a maximum 35 cycles (up to 2 years treatment). Additional dose given during the induction period on Day 8 of cycles 1 and 2. Each patient can be treated for a maximum of 37 administrations in total (up to 2 years treatment). Pembrolizumab 200 mg intravenously every 3 weeks for a maximum of 35 cycles.	Drug: IO102-IO103; IO102-IO103 comprises IDO peptide antigen (IO102) and PD-L1 peptide antigen (IO103) emulsified with adjuvant (Montanide ISA 51 VG) administered subcutaneously; Drug: Pembrolizumab; Pembrolizumab administered intravenously
Active Comparator: pembrolizumab; Pembrolizumab 200 mg intravenously every 3 weeks for a maximum of 35 cycles (up to 2 years treatment).	Drug: Pembrolizumab; Pembrolizumab administered intravenously

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression Free Survival (PFS)	PFS defined as the time from randomization to the first documented disease progression ((based on Independent Review Committee in accordance with RECIST v1.1) or death from any cause.	Approximately 3.5 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Complete response rate (CRR)	Percentage of patients with a visit response of CR, which will be determined by the IRC in accordance with RECIST v1.1.	Approximately 3.5 years
Duration of response (DoR)	DoR will be measured from the date of first observed objective response until disease progression or death (whichever is earlier) (based on IRC).	Approximately 3.5 years
Time to response (TTR)	TTR is defined as the time from the date of randomization to the date of first observed PR or CR (based on IRC).	Approximately 3.5 years
Time to complete response (TTCR)	TTCR is defined as the time from the date of randomization to the date of first observed CR (based on IRC).	Approximately 3.5 years
Disease control rate (DCR)	DCR is defined as the percentage of patients achieving a PR or CR or SD (based on IRC).	Approximately 3.5 years
Incidence of e.g. AEs and SAEs (Safety and Tolerability)	Incidence of AEs and SAEs, and treatment related AEs and SAEs. Incidence of AEs causing discontinuation of trial treatment.	Approximately 3.5 years
Overall Response Rate (ORR)	ORR defined as the percentage of patients achieving a confirmed PR or CR. ORR will be determined by an IRC in accordance with RECIST v1.1.	Approximately 2.5 years
Overall survival (OS)	OS defined as the time from randomisation until death from any cause. months. This will be determined by an IRC in accordance with RECIST v1.1.	Approximately 5.5 years
Durable Objective response rate (DRR)	DRR is defined as the percentage of patients achieving a PR or CR > 6 months. This will be determined by an IRC in accordance with RECIST v1.1.	Approximately 3.5 years

Collaborators and Investigators

• Sponsor: IO Biotech
• Collaborators: Merck Sharp & Dohme LLC; Syneos Health
• Investigators: Principal Investigator: Inge Marie Svane, MD, Prof, Institut for Klinisk Medicin, Herlev-Gentofte Hospital; Denmark

Study record dates

Study Major Dates

• Study Start (Actual): May 17, 2022
• Primary Completion (Actual): May 30, 2025
• Study Completion (Estimated): September 1, 2027

Study Registration Dates

• First Submitted: November 30, 2021
• First Submitted That Met QC Criteria: November 30, 2021
• First Posted (Actual): December 13, 2021

Study Record Updates

• Last Update Posted (Estimated): August 28, 2025
• Last Update Submitted That Met QC Criteria: August 21, 2025
• Last Verified: May 1, 2025

More Information

Terms related to this study

• Keywords: Immunotherapy; Pembrolizumab; Metastatic melanoma; Unresectable melanoma; Progression free survival; IO102-IO103
• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Neoplasms by Histologic Type; Skin Diseases; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Neuroendocrine Tumors; Nevi and Melanomas; Skin Neoplasms; Skin and Connective Tissue Diseases; Melanoma; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Antineoplastic Agents, Immunological; Immune Checkpoint Inhibitors; pembrolizumab
• Other Study ID Numbers: IO102-IO103-013 / KEYNOTE-D18; 2021-004594-32 (EudraCT Number)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No