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

Metastatic Melanoma Clinical Trial

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)

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT05155254
• Other study ID #: IO102-IO103-013 / KEYNOTE-D18
• Secondary ID: 2021-004594-32
• Status: Active, not recruiting
• Phase: Phase 3
• Start date: May 17, 2022
• Est. completion date: September 2027

Study information

• Verified date: January 2024
• Source: IO Biotech
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 407
• Est. completion date: September 2027
• Est. primary completion date: July 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Melanoma
• Metastatic Melanoma
• Unresectable Melanoma

Intervention

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
• Pembrolizumab
Pembrolizumab administered intravenously

Locations

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

Sponsors (3)

Lead Sponsor	Collaborator
IO Biotech	Merck Sharp & Dohme LLC, Syneos Health

Countries where clinical trial is conducted

United States,  Australia,  Belgium,  Czechia,  Denmark,  France,  Germany,  Hungary,  Israel,  Italy,  Netherlands,  Poland,  South Africa,  Spain,  Turkey,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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