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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT03070392




Registration number
NCT03070392
Ethics application status
Date submitted
14/02/2017
Date registered
3/03/2017
Date last updated
21/04/2020

Titles & IDs
Public title
Safety and Efficacy of IMCgp100 Versus Investigator Choice in Advanced Uveal Melanoma
Scientific title
A Phase II Randomized, Open-label, Multi-center Study of the Safety and Efficacy of IMCgp100 Compared With Investigator Choice in HLA-A*0201 Positive Patients With Previously Untreated Advanced Uveal Melanoma
Secondary ID [1] 0 0
IMCgp100-202
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Uveal Melanoma 0 0
Condition category
Condition code
Cancer 0 0 0 0
Malignant melanoma
Cancer 0 0 0 0
Other cancer types
Eye 0 0 0 0
Diseases / disorders of the eye

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Other interventions - IMCgp100
Treatment: Drugs - Dacarbazine
Other interventions - Ipilimumab
Other interventions - Pembrolizumab

Experimental: IMCgp100 - Biologic:IMCgp100 (Soluble gp 100-specific T cell receptor with anti - CD3 scFV: IMCgp100)

Active Comparator: Investigator's Choice - 1 of 3 Investigator's Choice options: Systemic Dacarbazine
1 of 3 Investigator's Choice options: Systemic Ipilimumab
1 of 3 Investigator's Choice options: Systemic Pembrolizumab


Other interventions: IMCgp100
IMCgp100 is to be administered at 20 mcg cycle 1 day1, then 30 mcg cycle 1 day 8, then 68 mcg cycle 1 day 15 and weekly thereafter by IV infusion over 15 minutes until confirmed disease progression or unacceptable toxicity

Treatment: Drugs: Dacarbazine
Dacarbazine is to be administered at 1,000 mg/m2 of body surface area IV infusion every 3 weeks until disease progression or unacceptable toxicity

Other interventions: Ipilimumab
Ipilimumab is to be administered at 3 mg/kg IV infusion over 90 minutes every 3 weeks for a total of 4 treatments

Other interventions: Pembrolizumab
Pembrolizumab is to be administered at 2 mg/kg IV infusion over 30 minutes every 3 weeks until confirmed disease progression or unacceptable toxicity

Intervention code [1] 0 0
Other interventions
Intervention code [2] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Overall survival defined as the time from patient inclusion to date of death due to any cause
Timepoint [1] 0 0
Survival status will be assessed every 3 months from randomization until death, assessed up to 40 months.
Secondary outcome [1] 0 0
Safety defined as the number of patients with treatment emergent adverse events, laboratory abnormalities, ECG changes, and/or physical examination findings
Timepoint [1] 0 0
Safety will be assessed from informed consent through 90 days after end of treatment
Secondary outcome [2] 0 0
Efficacy: Objective response rate (ORR) defined as the proportion of patients achieving an objective response (RECIST v1.1) by Independent Central Review
Timepoint [2] 0 0
ORR will be assessed every 3 months from randomization until disease progression, assessed up to 40 months
Secondary outcome [3] 0 0
Efficacy: Duration of response (DOR) defined as the time from first documented objective response (RECIST v1.1) by Independent Central Review until the date of documented disease progression
Timepoint [3] 0 0
DOR will be assessed every 3 months from randomization until disease progression, assessed up to 40 months
Secondary outcome [4] 0 0
Efficacy: Progression free survival (PFS) defined as the time from randomization to the date of progression (RECIST v1.1) by Independent Central Review or death due to any cause
Timepoint [4] 0 0
PFS will be assessed every 3 months from randomization until disease progression or death, assessed up to 40 months
Secondary outcome [5] 0 0
Efficacy: Disease control rate (DCR) defined as the proportion of patients with either an objective response or stable disease (RECIST v1.1) by Independent Central Review.
Timepoint [5] 0 0
DCR will be assessed every 3 months from randomization until disease progression, assessed up to 40 months
Secondary outcome [6] 0 0
Quality-of-Life: General health status will be assessed using the EQ-5D,5L questionnaire
Timepoint [6] 0 0
: EQ-5D,5L will be assessed every 6 weeks from randomization for 24 weeks and approximately every 3 months thereafter until death, assessed up to 40 months
Secondary outcome [7] 0 0
Quality-of-Life: Health related quality of life will be assessed using EORTC QLQ-C30 questionnaire
Timepoint [7] 0 0
EORTC QLQ-C30 will be assessed every 6 weeks from randomization for 24 weeks and approximately every 3 months thereafter until disease progression, assessed up to 40 months
Secondary outcome [8] 0 0
Pharmacokinetics (IMCgp100 Arm only): Area under the plasma concentration-time curve (AUC)
Timepoint [8] 0 0
AUC will be assessed weekly for 3 weeks and every 6 weeks thereafter until end of treatment, assessed up to 40 months
Secondary outcome [9] 0 0
Pharmacokinetics (IMCgp100 Arm only): The maximum observed plasma drug concentration after single dose administration (Cmax)
Timepoint [9] 0 0
Cmax will be assessed weekly for 3 weeks and every 6 weeks thereafter until end of treatment, assessed up to 40 months
Secondary outcome [10] 0 0
Pharmacokinetics (IMCgp100 Arm only): The time to reach maximum plasma concentration (Tmax)
Timepoint [10] 0 0
Tmax will be assessed prior to and after the first three doses of IMCgp100, an average of 3 weeks
Secondary outcome [11] 0 0
Pharmacokinetics (IMCgp100 Arm only): The elimination half-life (t1/2)
Timepoint [11] 0 0
t1/2 will be assessed prior to and after the first three doses of IMCgp100, an average of 3 weeks
Secondary outcome [12] 0 0
Pharmacokinetics (IMCgp100 Arm only): To assess the frequency of anti-IMCgp100 antibody formation
Timepoint [12] 0 0
Approximately 5 assessments will be performed between first dose of IMCgp100 and end of treatment, assessed up to 40 months

Eligibility
Key inclusion criteria
1. Male or female patients age = 18 years of age at the time of informed consent

2. Ability to provide and understand written informed consent prior to any study
procedures

3. Histologically or cytologically confirmed metastatic UM

4. No prior systemic therapy in the metastatic or advanced setting

5. No prior local, liver-directed therapy; prior surgical resection of oligometastatic
liver disease is allowed

6. Prior neoadjuvant or adjuvant therapy is allowed provided administered in the curative
setting in patients with localized disease
Minimum age
18 Years
Maximum age
99 Years
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Impaired baseline organ function as evaluated by out-of-range laboratory values

2. History of severe hypersensitivity reactions (eg, anaphylaxis) to other biologic drugs
or monoclonal antibodies

3. Clinically significant cardiac disease or impaired cardiac function

4. Presence of symptomatic or untreated central nervous system (CNS) metastases

5. Active infection requiring systemic antibiotic therapy

6. Known history of human immunodeficiency virus infection (HIV)

7. Active hepatitis B virus (HBV) or hepatitis C virus (HCV) infection

8. Malignant disease, other than that being treated in this study

9. Patients receiving systemic steroid therapy or any other systemic immunosuppressive
medication. Local steroid therapies are acceptable

10. History of adrenal insufficiency, pneumonitis, interstitial lung disease, or
inflammatory bowel disease

11. Major surgery within 2 weeks of the first dose of study drug

12. Radiotherapy within 2 weeks of the first dose of study drug, with the exception of
palliative radiotherapy to a limited field

13. Use of hematopoietic colony-stimulating growth factors (eg, G-CSF, GM-CSF, M-CSF) = 2
weeks prior to start of study drug

14. Pregnant, likely to become pregnant, or lactating women

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 2
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,SA,VIC
Recruitment hospital [1] 0 0
Saint Vincents Hospital - Darlinghurst
Recruitment hospital [2] 0 0
Melanoma Institute of Australia - Wollstonecraft
Recruitment hospital [3] 0 0
Central Adelaide Local Health Network, Royal Adelaide Hospital Cancer Center - Adelaide
Recruitment hospital [4] 0 0
Peter MacCallum Cancer Center - Melbourne
Recruitment postcode(s) [1] 0 0
2010 - Darlinghurst
Recruitment postcode(s) [2] 0 0
2065 - Wollstonecraft
Recruitment postcode(s) [3] 0 0
5000 - Adelaide
Recruitment postcode(s) [4] 0 0
3000 - Melbourne
Recruitment outside Australia
Country [1] 0 0
United States of America
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California
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Colorado
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Florida
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Georgia
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Illinois
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Iowa
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Massachusetts
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United States of America
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Missouri
Country [9] 0 0
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New York
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United States of America
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North Carolina
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Ohio
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Oklahoma
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Oregon
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Pennsylvania
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United States of America
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Texas
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Belgium
State/province [16] 0 0
Bruxelles
Country [17] 0 0
Canada
State/province [17] 0 0
Alberta
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Canada
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Toronto
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France
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Nice
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France
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Paris
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Germany
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Nordrhein Westfalen
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Germany
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Berlin
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Germany
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Dresden
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Germany
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Essen
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Germany
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Hamburg
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Germany
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Heidelberg
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Germany
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Munich
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Italy
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Milan
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Italy
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Napoli
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Netherlands
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Leiden
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Poland
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Warsaw
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Russian Federation
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Moscow
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Russian Federation
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Saint Petersburg
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Russian Federation
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Tomsk
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Russian Federation
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Volgograd
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Spain
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ES-Spain
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Spain
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Sevilla
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Switzerland
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Zürich
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Ukraine
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Dnipropetrovs'k
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Ukraine
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Kyiv
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Ukraine
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Uzhhorod
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Ukraine
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Zaporizhzhia
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United Kingdom
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Middlesex
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United Kingdom
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Wirral
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United Kingdom
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Glasgow

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Immunocore Ltd
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
To evaluate the overall survival of HLA-A*0201 positive adult patients with previously
untreated advanced UM receiving IMCgp100 compared to Investigator's Choice of dacarbazine,
ipilimumab, or pembrolizumab.
Trial website
https://clinicaltrials.gov/show/NCT03070392
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Mohammed Dar
Address 0 0
Immunocore Ltd
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Shaad Abdullah, MD
Address 0 0
Country 0 0
Phone 0 0
484-534-5261
Fax 0 0
Email 0 0
clinicaltrials@immunocore.com
Contact person for scientific queries

Summary results
For IPD and results data, please see https://clinicaltrials.gov/show/NCT03070392