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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/ct2/show/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:
Metastatic Melanoma 0 0
Unresectable Melanoma 0 0
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
Country [3] 0 0
United States of America
State/province [3] 0 0
Virginia
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Belgium
State/province [4] 0 0
Oost-Vlaanderen
Country [5] 0 0
Belgium
State/province [5] 0 0
Sint-Niklaas
Country [6] 0 0
Czechia
State/province [6] 0 0
Hradec Králové
Country [7] 0 0
Czechia
State/province [7] 0 0
Olomouc
Country [8] 0 0
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
Country [18] 0 0
France
State/province [18] 0 0
La Tronche
Country [19] 0 0
France
State/province [19] 0 0
Lille
Country [20] 0 0
France
State/province [20] 0 0
Marseille cedex 05
Country [21] 0 0
France
State/province [21] 0 0
Nice
Country [22] 0 0
France
State/province [22] 0 0
Pierre Benite
Country [23] 0 0
France
State/province [23] 0 0
Rennes Cedex
Country [24] 0 0
France
State/province [24] 0 0
Saint Herblain
Country [25] 0 0
France
State/province [25] 0 0
Valence
Country [26] 0 0
France
State/province [26] 0 0
Villejuif Cedex
Country [27] 0 0
Germany
State/province [27] 0 0
Augsburg
Country [28] 0 0
Germany
State/province [28] 0 0
Berlin
Country [29] 0 0
Germany
State/province [29] 0 0
Bochum
Country [30] 0 0
Germany
State/province [30] 0 0
Erlangen
Country [31] 0 0
Germany
State/province [31] 0 0
Essen
Country [32] 0 0
Germany
State/province [32] 0 0
Frankfurt
Country [33] 0 0
Germany
State/province [33] 0 0
Halle (Saale)
Country [34] 0 0
Germany
State/province [34] 0 0
Hamburg
Country [35] 0 0
Germany
State/province [35] 0 0
Heidelberg
Country [36] 0 0
Germany
State/province [36] 0 0
Heilbronn
Country [37] 0 0
Germany
State/province [37] 0 0
Kiel
Country [38] 0 0
Germany
State/province [38] 0 0
Mainz
Country [39] 0 0
Germany
State/province [39] 0 0
Mannheim
Country [40] 0 0
Germany
State/province [40] 0 0
Minden
Country [41] 0 0
Germany
State/province [41] 0 0
Muenchen
Country [42] 0 0
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
State/province [53] 0 0
Tel Hashomer
Country [54] 0 0
Italy
State/province [54] 0 0
Ancona
Country [55] 0 0
Italy
State/province [55] 0 0
Aviano
Country [56] 0 0
Italy
State/province [56] 0 0
Bari
Country [57] 0 0
Italy
State/province [57] 0 0
Candiolo
Country [58] 0 0
Italy
State/province [58] 0 0
Genova
Country [59] 0 0
Italy
State/province [59] 0 0
Meldola
Country [60] 0 0
Italy
State/province [60] 0 0
Milano
Country [61] 0 0
Italy
State/province [61] 0 0
Napoli
Country [62] 0 0
Italy
State/province [62] 0 0
Padova
Country [63] 0 0
Italy
State/province [63] 0 0
Perugia
Country [64] 0 0
Italy
State/province [64] 0 0
Roma
Country [65] 0 0
Italy
State/province [65] 0 0
Rome
Country [66] 0 0
Italy
State/province [66] 0 0
Siena
Country [67] 0 0
Netherlands
State/province [67] 0 0
Amsterdam
Country [68] 0 0
Netherlands
State/province [68] 0 0
Leiden
Country [69] 0 0
Netherlands
State/province [69] 0 0
Maastricht
Country [70] 0 0
Netherlands
State/province [70] 0 0
Rotterdam
Country [71] 0 0
Netherlands
State/province [71] 0 0
Utrecht
Country [72] 0 0
Poland
State/province [72] 0 0
Masovian
Country [73] 0 0
Poland
State/province [73] 0 0
Poznan
Country [74] 0 0
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
State/province [77] 0 0
A Coruña
Country [78] 0 0
Spain
State/province [78] 0 0
Barcelona
Country [79] 0 0
Spain
State/province [79] 0 0
Madrid
Country [80] 0 0
Spain
State/province [80] 0 0
Malaga
Country [81] 0 0
Spain
State/province [81] 0 0
Oviedo
Country [82] 0 0
Spain
State/province [82] 0 0
Pamplona
Country [83] 0 0
Spain
State/province [83] 0 0
Valencia
Country [84] 0 0
Spain
State/province [84] 0 0
Zaragoza
Country [85] 0 0
Turkey
State/province [85] 0 0
Adana
Country [86] 0 0
Turkey
State/province [86] 0 0
Ankara
Country [87] 0 0
Turkey
State/province [87] 0 0
Antalya
Country [88] 0 0
Turkey
State/province [88] 0 0
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
Other collaborator category [1] 0 0
Other
Name [1] 0 0
Syneos Health
Address [1] 0 0
Country [1] 0 0
Other collaborator category [2] 0 0
Commercial sector/Industry
Name [2] 0 0
Merck Sharp & Dohme LLC
Address [2] 0 0
Country [2] 0 0

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/ct2/show/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