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

Phase 3

Active, not recruiting

• Conditions: Metastatic Melanoma; Unresectable Melanoma
• Interventions: Drug: IO102-IO103; Drug: Pembrolizumab

• Registration Number: NCT05155254
• Lead Sponsor: IO Biotech

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.

Detailed Description

Not available

Basic Information
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Recruitment & Eligibility
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Study & Design
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Trial Locations
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Related News

Study Timeline

• Study First Submitted: 2021-11-30
• Study First Submitted QC: 2021-11-30
• Study First Posted: 2021-12-13
• Study Start: 2022-05-17
• Status Verified: 2024-01
• Last Update Submitted: 2024-01-08
• Last Update Posted: 2024-01-09
• Primary Completion: 2025-07
• Study Completion: 2027-09

Recruitment & Eligibility

• Status: ACTIVE_NOT_RECRUITING
• Sex: All
• Target Recruitment: 407

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.

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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.

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
IO102-IO103 + pembrolizumab	IO102-IO103	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.
IO102-IO103 + pembrolizumab	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.
pembrolizumab	Pembrolizumab	Pembrolizumab 200 mg intravenously every 3 weeks for a maximum of 35 cycles (up to 2 years treatment).

Primary Outcome Measures

Name	Time	Method
Progression Free Survival (PFS)	Approximately 3.5 years	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.

Secondary Outcome Measures

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

Trial Locations

Locations (110)

Erasmus MC; 🇳🇱 Rotterdam, Netherlands

Flinders Medical Centre; 🇦🇺 Bedford Park, South Australia, Australia

Herlev og Gentofte Hospital; 🇩🇰 Herlev, Denmark

Mid Florida Hematology and Oncology Center; 🇺🇸 Orange City, Florida, United States

Chu Grenoble - Hopital Albert Michallon; 🇫🇷 La Tronche, France

AZ Nikolaas; 🇧🇪 Sint-Niklaas, Belgium

Peter MacCallum Cancer Centre PMCC - East Melbourne; 🇦🇺 Melbourne, Australia

Centre Hospitalier Lyon Sud; 🇫🇷 Pierre Benite, France

Szpital Kliniczny im. Heliodora Święcickiego UM w Poznaniu; 🇵🇱 Poznan, Poland

Aarhus University Hospital; 🇩🇰 Aarhus, Denmark

Istituto Tumori Giovanni Paolo II IRCCS Ospedale Oncologico Bari; 🇮🇹 Bari, Italy

Centre Hospitalier Universitaire de Besançon Jean Minjoz; 🇫🇷 Besancon, France

Hopital Ambroise; 🇫🇷 Boulogne Billancourt, France

Centre Georges Francois Leclerc; 🇫🇷 Dijon, France

Elbe Klinikum Buxtehude; 🇩🇪 Hamburg, Germany

Nationales Centrum fr Tumorerkrankungen NCT; 🇩🇪 Heidelberg, Germany

Department of Dermatology University of Mainz; 🇩🇪 Mainz, Germany

Rabin Medical Center; 🇮🇱 Petah Tikva, Israel

Hetenyi G Korhaz, Onkologiai Kozpont; 🇭🇺 Szolnok, Hungary

VCU Massey Cancer Center; 🇺🇸 Richmond, Virginia, United States

Cairns Hospital; 🇦🇺 Cairns, Queensland, Australia

Roswell Park Cancer Institute; 🇺🇸 Buffalo, New York, United States

Westmead Hospital; 🇦🇺 Westmead, New South Wales, Australia

Southern Medical Day Care Centre; 🇦🇺 Wollongong, New South Wales, Australia

Border Medical Oncology Research Unit; 🇦🇺 Albury, New South Wales, Australia

Sunshine Coast University Hospital; 🇦🇺 Birtinya, Australia

The Queen Elizabeth Hospital; 🇦🇺 Woodville South, South Australia, Australia

Universitair Ziekenhuis Gent UZ Gent; 🇧🇪 Gent, Oost-Vlaanderen, Belgium

FNHK Klinika onkologie a radioterapie; 🇨🇿 Hradec Králové, Czechia

Fakultni Nemocnice Olomouc; 🇨🇿 Olomouc, Czechia

FN Ostrava; 🇨🇿 Ostrava, Czechia

Universitaetsklinikum Schleswig-Holstein; 🇩🇪 Kiel, Germany

Aalborg University Hospital; 🇩🇰 Aalborg, Denmark

FNKV Department of Dermatology; 🇨🇿 Praha, Czechia

Odense University Hospital; 🇩🇰 Odense, Denmark

Hôpital de La Timone; 🇫🇷 Marseille cedex 05, France

Centre Hospitalier Universitaire de Bordeaux Hospital Saint Andre; 🇫🇷 Bordeaux, France

CHU de Nice Hpital de lArchet 2; 🇫🇷 Nice, France

Centre Hospitalier Universitaire de Lille; 🇫🇷 Lille, France

Centre Eugene Marquis; 🇫🇷 Rennes Cedex, France

Institut de Cancérologie de L'Ouest; 🇫🇷 Saint Herblain, France

Centre Hospitalier de Valence (CHV); 🇫🇷 Valence, France

Gustave Roussy; 🇫🇷 Villejuif Cedex, France

Charite Universitaetsmedizin Berlin; 🇩🇪 Berlin, Germany

Universitatsklinikum Augsburg Medizincampus Sued; 🇩🇪 Augsburg, Germany

St. Josef Hospital - Ruhr-Universitt Bochum; 🇩🇪 Bochum, Germany

Universitaetsklinikum Essen; 🇩🇪 Essen, Germany

University Hospital Erlangen; 🇩🇪 Erlangen, Germany

SLK-Kliniken Heilbronn GmbH; 🇩🇪 Heilbronn, Germany

University Hospital Frankfurt Theodor-Stern-Kai; 🇩🇪 Frankfurt, Germany

Universitatsklinik fur Dermatologie und Venerologie der MLU Halle-Wittenberg; 🇩🇪 Halle (Saale), Germany

Universitatsmedizin Mannheim Dermatologie; 🇩🇪 Mannheim, Germany

Mühlenkreiskliniken AöR, University Hospital Ruhr University Bochum Campus Minden; 🇩🇪 Minden, Germany

LMU Muenchen; 🇩🇪 Muenchen, Germany

Hospital Tubingen; 🇩🇪 Tubingen, Germany

Universitaetsklinikum Muenster; 🇩🇪 Münster, Germany

Universittsklinikum Wuerzburg; 🇩🇪 Wuerzburg, Germany

Orszagos Onkologiai Intezet; 🇭🇺 Budapest, Hungary

Bor, -Nemikortani es Onkodermatologiai Klinika; 🇭🇺 Pecs, Hungary

Ben-Gurion University of the Negev - Soroka University Medical Center - Soroka Clinical Research Center; 🇮🇱 Beer Sheva, Israel

Emek Medical Center; 🇮🇱 Afula, Israel

Hadassah University Hospital; 🇮🇱 Jerusalem, Israel

The Chaim Sheba Medical Center - The Ella Lemelbaum Institute for Immuno-Oncology; 🇮🇱 Tel Hashomer, Israel

Tel Aviv Sourasky Medical Center; 🇮🇱 Tel Aviv-Yafo, Israel

Clinica Oncologica, AOU Riuniti ancona; 🇮🇹 Ancona, Italy

Centro di Riferimento Oncologico; 🇮🇹 Aviano, Italy

IRCCS Ospedale San Raffaele; 🇮🇹 Candiolo, Italy

Istituto Romagnolo per lo Studio dei Tumori " DINO AMADORI"; 🇮🇹 Meldola, Italy

IRCCS Ospedale Policlinico San Martino; 🇮🇹 Genova, Italy

Fondazione IRCCS Istituto Nazionale dei Tumori; 🇮🇹 Milano, Italy

Istituto Nazionale Tumori IRCCS Fondazione Pascale; 🇮🇹 Napoli, Italy

Veneto Oncology Institute; 🇮🇹 Padova, Italy

IRCCS Istituti Fisioterapici Ospitalieri; 🇮🇹 Roma, Italy

Ospedale S. Maria della Misericordia; 🇮🇹 Perugia, Italy

Idi-Irccs; 🇮🇹 Rome, Italy

LUMC; 🇳🇱 Leiden, Netherlands

The Netherlands Cancer Institute; 🇳🇱 Amsterdam, Netherlands

UMC Maastricht; 🇳🇱 Maastricht, Netherlands

Azienda Ospedaliera Universitaria Senese Policlinico Le Scotte; 🇮🇹 Siena, Italy

AMC Amsterdam, locatie VUMC; 🇳🇱 Amsterdam, Netherlands

Mary Potter Oncology Centre Groenkloof; 🇿🇦 Pretoria, South Africa

Cape Town Oncology Trials (Pty) Ltd.; 🇿🇦 Cape Town, South Africa

Hospital Universitario Virgen Macarena; 🇪🇸 Seville, Andalusia, Spain

Instituto Oncologico Dr. Rosell IOR - Hospital Universitari Quiron Dexeus; 🇪🇸 Barcelona, Spain

CH Universitario de A Coruña (CHUAC); 🇪🇸 A Coruña, Spain

Hospital Clinic i Provincial; 🇪🇸 Barcelona, Spain

Hospital General Universitario Gregorio Marañon; 🇪🇸 Madrid, Spain

Hospital Vall d'hebron; 🇪🇸 Barcelona, Spain

Hospital Universitari Germans Trias i Pujol HUGTP, ICO-Badalona; 🇪🇸 Barcelona, Spain

Hospital Regional Universitario de Malaga; 🇪🇸 Malaga, Spain

Clinica Universidad de Navarra; 🇪🇸 Pamplona, Spain

Hospital Universitario HM Sanchinarro; 🇪🇸 Madrid, Spain

Hospital Universitario Ramon y Cajal; 🇪🇸 Madrid, Spain

Istanbul University-Cerrahpasa, Cerrahpasa Medical Faculty; 🇹🇷 Istanbul, Turkey

Hospital Universitario Central de Asturias (HUCA); 🇪🇸 Oviedo, Spain

Adana City Education and Research Hospital; 🇹🇷 Adana, Turkey

Miguel Servet University Hospital; 🇪🇸 Zaragoza, Spain

Hospital General Universitario de Valencia; 🇪🇸 Valencia, Spain

Memorial Ankara Hospital; 🇹🇷 Ankara, Turkey

Hospital Universitari i Politecnic La Fe; 🇪🇸 Valencia, Spain

Akdeniz University Medical Faculty; 🇹🇷 Antalya, Turkey

Gulhane School of Medicine; 🇹🇷 Ankara, Turkey

Ege university Faculty of Medicine, T. Aktas Oncology Hospital, Bornova; 🇹🇷 Bornova, Turkey

Goztepe Prof. Dr. Suleyman Yalcin Sehir Hastanesi; 🇹🇷 Istanbul, Turkey

Oxford University Hospitals NHS Foundation Trust; 🇬🇧 Oxford, United Kingdom

Christie Hospital NHS Trust; 🇬🇧 Manchester, United Kingdom

Maria Sklodowska-Curie National Research Institute of Oncology; 🇵🇱 Warsaw, Masovian, Poland

Orlando Health Cancer Institute; 🇺🇸 Orlando, Florida, United States

Guy's Hospital; 🇬🇧 London, United Kingdom

University Medical Center Utrecht; 🇳🇱 Utrecht, Netherlands