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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT05155254




Registration number
NCT05155254
Ethics application status
Date submitted
30/11/2021
Date registered
13/12/2021
Date last updated
9/01/2024

Titles & IDs
Public title
IO102-IO103 in Combination With Pembrolizumab Versus Pembrolizumab Alone in Advanced Melanoma (IOB-013 / KN-D18)
Scientific 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)
Secondary ID [1] 0 0
2021-004594-32
Secondary ID [2] 0 0
IO102-IO103-013 / KEYNOTE-D18
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Condition category
Condition code
Cancer 0 0 0 0
Malignant melanoma

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - IO102-IO103
Treatment: Drugs - Pembrolizumab

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.

Active Comparator: pembrolizumab - Pembrolizumab 200 mg intravenously every 3 weeks for a maximum of 35 cycles (up to 2 years treatment).


Treatment: Drugs: IO102-IO103
IO102-IO103 comprises IDO peptide antigen (IO102) and PD-L1 peptide antigen (IO103) emulsified with adjuvant (Montanide ISA 51 VG) administered subcutaneously

Treatment: Drugs: Pembrolizumab
Pembrolizumab administered intravenously
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Progression Free Survival (PFS)
Timepoint [1] 0 0
Approximately 3.5 years
Secondary outcome [1] 0 0
Overall Response Rate (ORR)
Timepoint [1] 0 0
Approximately 2.5 years
Secondary outcome [2] 0 0
Overall survival (OS)
Timepoint [2] 0 0
Approximately 5.5 years
Secondary outcome [3] 0 0
Durable Objective response rate (DRR)
Timepoint [3] 0 0
Approximately 3.5 years
Secondary outcome [4] 0 0
Complete response rate (CRR)
Timepoint [4] 0 0
Approximately 3.5 years
Secondary outcome [5] 0 0
Duration of response (DoR)
Timepoint [5] 0 0
Approximately 3.5 years
Secondary outcome [6] 0 0
Time to response (TTR)
Timepoint [6] 0 0
Approximately 3.5 years
Secondary outcome [7] 0 0
Time to complete response (TTCR)
Timepoint [7] 0 0
Approximately 3.5 years
Secondary outcome [8] 0 0
Disease control rate (DCR)
Timepoint [8] 0 0
Approximately 3.5 years
Secondary outcome [9] 0 0
Incidence of e.g. AEs and SAEs (Safety and Tolerability)
Timepoint [9] 0 0
Approximately 3.5 years

Eligibility
Key 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.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key 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 design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Active, not recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
17/05/2022
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
1/09/2027
Actual
Sample size
Target
Accrual to date
Final
407
Recruitment in Australia
Recruitment state(s)
NSW,QLD,SA
Recruitment hospital [1] 0 0
Border Medical Oncology Research Unit - Albury
Recruitment hospital [2] 0 0
Westmead Hospital - Westmead
Recruitment hospital [3] 0 0
Southern Medical Day Care Centre - Wollongong
Recruitment hospital [4] 0 0
Cairns Hospital - Cairns
Recruitment hospital [5] 0 0
Flinders Medical Centre - Bedford Park
Recruitment hospital [6] 0 0
The Queen Elizabeth Hospital - Woodville South
Recruitment hospital [7] 0 0
Sunshine Coast University Hospital - Birtinya
Recruitment hospital [8] 0 0
Peter MacCallum Cancer Centre PMCC - East Melbourne - Melbourne
Recruitment postcode(s) [1] 0 0
2640 - Albury
Recruitment postcode(s) [2] 0 0
2145 - Westmead
Recruitment postcode(s) [3] 0 0
2500 - Wollongong
Recruitment postcode(s) [4] 0 0
4870 - Cairns
Recruitment postcode(s) [5] 0 0
5042 - Bedford Park
Recruitment postcode(s) [6] 0 0
5011 - Woodville South
Recruitment postcode(s) [7] 0 0
4575 - Birtinya
Recruitment postcode(s) [8] 0 0
3052 - Melbourne
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Florida
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United States of America
State/province [2] 0 0
New York
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United States of America
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Virginia
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Belgium
State/province [4] 0 0
Oost-Vlaanderen
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Belgium
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Sint-Niklaas
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Czechia
State/province [6] 0 0
Hradec Králové
Country [7] 0 0
Czechia
State/province [7] 0 0
Olomouc
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Czechia
State/province [8] 0 0
Ostrava
Country [9] 0 0
Czechia
State/province [9] 0 0
Praha
Country [10] 0 0
Denmark
State/province [10] 0 0
Aalborg
Country [11] 0 0
Denmark
State/province [11] 0 0
Aarhus
Country [12] 0 0
Denmark
State/province [12] 0 0
Herlev
Country [13] 0 0
Denmark
State/province [13] 0 0
Odense
Country [14] 0 0
France
State/province [14] 0 0
Besancon
Country [15] 0 0
France
State/province [15] 0 0
Bordeaux
Country [16] 0 0
France
State/province [16] 0 0
Boulogne Billancourt
Country [17] 0 0
France
State/province [17] 0 0
Dijon
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France
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La Tronche
Country [19] 0 0
France
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Lille
Country [20] 0 0
France
State/province [20] 0 0
Marseille cedex 05
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France
State/province [21] 0 0
Nice
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France
State/province [22] 0 0
Pierre Benite
Country [23] 0 0
France
State/province [23] 0 0
Rennes Cedex
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France
State/province [24] 0 0
Saint Herblain
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France
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Valence
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France
State/province [26] 0 0
Villejuif Cedex
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Germany
State/province [27] 0 0
Augsburg
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Germany
State/province [28] 0 0
Berlin
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Germany
State/province [29] 0 0
Bochum
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Germany
State/province [30] 0 0
Erlangen
Country [31] 0 0
Germany
State/province [31] 0 0
Essen
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Germany
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Frankfurt
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Germany
State/province [33] 0 0
Halle (Saale)
Country [34] 0 0
Germany
State/province [34] 0 0
Hamburg
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Germany
State/province [35] 0 0
Heidelberg
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Germany
State/province [36] 0 0
Heilbronn
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Germany
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Kiel
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Germany
State/province [38] 0 0
Mainz
Country [39] 0 0
Germany
State/province [39] 0 0
Mannheim
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Germany
State/province [40] 0 0
Minden
Country [41] 0 0
Germany
State/province [41] 0 0
Muenchen
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Germany
State/province [42] 0 0
Münster
Country [43] 0 0
Germany
State/province [43] 0 0
Tubingen
Country [44] 0 0
Germany
State/province [44] 0 0
Wuerzburg
Country [45] 0 0
Hungary
State/province [45] 0 0
Budapest
Country [46] 0 0
Hungary
State/province [46] 0 0
Pecs
Country [47] 0 0
Hungary
State/province [47] 0 0
Szolnok
Country [48] 0 0
Israel
State/province [48] 0 0
Afula
Country [49] 0 0
Israel
State/province [49] 0 0
Beer Sheva
Country [50] 0 0
Israel
State/province [50] 0 0
Jerusalem
Country [51] 0 0
Israel
State/province [51] 0 0
Petah Tikva
Country [52] 0 0
Israel
State/province [52] 0 0
Tel Aviv-Yafo
Country [53] 0 0
Israel
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Tel Hashomer
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Italy
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Ancona
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Italy
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Aviano
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Italy
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Bari
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Italy
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Candiolo
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Italy
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Genova
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Italy
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Meldola
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Italy
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Milano
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Italy
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Napoli
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Italy
State/province [62] 0 0
Padova
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Italy
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Perugia
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Italy
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Roma
Country [65] 0 0
Italy
State/province [65] 0 0
Rome
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Italy
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Siena
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Netherlands
State/province [67] 0 0
Amsterdam
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Netherlands
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Leiden
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Netherlands
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Maastricht
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Netherlands
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Rotterdam
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Netherlands
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Utrecht
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Poland
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Masovian
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Poland
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Poznan
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South Africa
State/province [74] 0 0
Cape Town
Country [75] 0 0
South Africa
State/province [75] 0 0
Pretoria
Country [76] 0 0
Spain
State/province [76] 0 0
Andalusia
Country [77] 0 0
Spain
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A Coruña
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Spain
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Barcelona
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Spain
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Madrid
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Spain
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Malaga
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Spain
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Oviedo
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Spain
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Pamplona
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Spain
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Valencia
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Spain
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Zaragoza
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Turkey
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Adana
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Turkey
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Ankara
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Turkey
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Antalya
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Turkey
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Bornova
Country [89] 0 0
Turkey
State/province [89] 0 0
Istanbul
Country [90] 0 0
United Kingdom
State/province [90] 0 0
London
Country [91] 0 0
United Kingdom
State/province [91] 0 0
Manchester
Country [92] 0 0
United Kingdom
State/province [92] 0 0
Oxford

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
IO Biotech
Address
Country

Ethics approval
Ethics application status

Summary
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.
Trial website
https://clinicaltrials.gov/study/NCT05155254
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Inge Marie Svane, MD, Prof
Address 0 0
Institut for Klinisk Medicin, Herlev-Gentofte Hospital; Denmark
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/study/NCT05155254