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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/NCT03070392




Registration number
NCT03070392
Ethics application status
Date submitted
14/02/2017
Date registered
3/03/2017
Date last updated
8/03/2024

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(has expanded access)
Description of intervention(s) / exposure
Other interventions - IMCgp100
Treatment: Drugs - Dacarbazine
Other interventions - Ipilimumab
Other interventions - Pembrolizumab

Experimental: IMCgp100 (tebentafusp, Kimmtrak) - 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 up to a maximum of 200 mg administered Intravenously over 30 minutes every 3 weeks or 200 mg fixed dose administered intravenously every 3 weeks where approved locally 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
Efficacy: Overall Survival
Timepoint [1] 0 0
From randomization to the data cut off date of 13-Oct-2020; median follow-up duration was 14.1 months.
Secondary outcome [1] 0 0
Safety: Number of Participants With Treatment Emergent Adverse Events
Timepoint [1] 0 0
Safety was assessed from informed consent through 90 days after end of treatment, up to 36 months.
Secondary outcome [2] 0 0
Efficacy: Progression Free Survival (PFS)
Timepoint [2] 0 0
PFS was assessed every 3 months from randomization until disease progression or death, up to 36 months.
Secondary outcome [3] 0 0
Quality-of-Life: Change From Baseline in EQ-5D,5L Domain Scores
Timepoint [3] 0 0
EQ-5D,5L was assessed at baseline (Cycle 1 Day 1) and on Day 1 of every other cycle to Cycle 5 Day 1, every fourth cycle thereafter, beginning with Cycle 9 Day 1 and End of Treatment (EOT), up to 36 months. Each cycle is 21 days.
Secondary outcome [4] 0 0
Quality-of-life: Change From Baseline in EQ-5D Visual Analogue Score (VAS)
Timepoint [4] 0 0
EQ-5D,5L VAS was assessed at baseline (Cycle 1 Day 1) and on Day 1 of every other cycle to Cycle 5 Day 1, every fourth cycle thereafter, beginning with Cycle 9 Day 1 and End of Treatment (EOT), up to 36 months. Each cycle is 21 days.
Secondary outcome [5] 0 0
Quality-of-Life: Change From Baseline in EORTC QLQ-C30 Global Health Status
Timepoint [5] 0 0
EORTC QLQ-C30 was assessed at baseline (Cycle 1 Day 1) and on Day 1 of every other cycle to Cycle 5 Day 1, every fourth cycle thereafter, beginning with Cycle 9 Day 1 and End of Treatment (EOT), up to 36 months. Each cycle is 21 days.
Secondary outcome [6] 0 0
Pharmacokinetics (PK): Tebentafusp Concentration
Timepoint [6] 0 0
PK concentrations were assessed at pre-dose, end of infusion and anytime in the 12 to 24 hour window after completion of the infusion in Cycle 1 on Days 1, 8 and 15.
Secondary outcome [7] 0 0
Efficacy: Objective Response Rate (ORR)
Timepoint [7] 0 0
ORR will be assessed after every participant has had at least 3 assessments, conducted every 3 months, up to 5.5 years.
Secondary outcome [8] 0 0
Efficacy: Duration of Response (DOR)
Timepoint [8] 0 0
DOR will be assessed every 3 months from randomization until disease progression, assessed up to 5.5 years.
Secondary outcome [9] 0 0
Efficacy: Disease Control Rate (DCR)
Timepoint [9] 0 0
DCR will be assessed every 3 months from randomization until disease progression, up to 5.5 years.
Secondary outcome [10] 0 0
Pharmacokinetics: Frequency of Anti-IMCgp100 Antibody Formation
Timepoint [10] 0 0
Approximately 5 assessments will be performed between first dose of IMCgp100 and end of treatment, assessed up to 5.5 years.

Eligibility
Key inclusion criteria
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. Must meet the following criteria related to prior treatment:

- No prior systemic therapy in the metastatic or advanced setting including
chemotherapy, immunotherapy, or targeted therapy

- No prior regional, liver-directed therapy including chemotherapy, radiotherapy,
or embolization

- Prior surgical resection of oligometastatic disease is allowed

- Prior neoadjuvant or adjuvant therapy is allowed provided administered in the
curative setting in patients with localized disease. Patients may not be
re-treated with an Investigator's Choice therapy that was administered as
adjuvant or neoadjuvant treatment. Additionally, patients who have received
nivolumab as prior adjuvant/neoadjuvant treatment should not receive
pembrolizumab as Investigator's Choice therapy.

5. HLA A*0201 positive by central assay

6. Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1 at Screening

7. Patients have measurable disease or non-measurable disease according to RECIST v1.1

8. All other relevant medical conditions must be well-managed and stable, in the opinion
of the investigator, for at least 28 days prior to first administration of study drug
Minimum age
18 Years
Maximum age
99 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Exclusion Criteria

1. 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, or CNS
metastases that require doses of corticosteroids within the prior 3 weeks to study Day
1. Patients with brain metastases are eligible if lesions have been treated with
localized therapy and there is no evidence of PD for at least 4 weeks by magnetic
resonance imaging (MRI) prior to the first dose of study drug

5. Active infection requiring systemic antibiotic therapy. Patients requiring systemic
antibiotics for infection must have completed therapy at least 1 week prior to the
first dose of study drug

6. Known history of human immunodeficiency virus infection (HIV). Testing for HIV status
is not necessary unless clinically indicated

7. Active hepatitis B virus (HBV) or hepatitis C virus (HCV) infection per institutional
protocol. Testing for HBV or HCV status is not necessary unless clinically indicated
or the patient has a history of HBV or HCV infection

8. Malignant disease, other than that being treated in this study. Exceptions to this
exclusion include the following: malignancies that were treated curatively and have
not recurred within 2 years prior to study treatment; completely resected basal cell
and squamous cell skin cancers; any malignancy considered to be indolent and that has
never required therapy; and completely resected carcinoma in situ of any type

9. Any medical condition that would, in the investigator's or Sponsor's judgment, prevent
the patient's participation in the clinical study due to safety concerns, compliance
with clinical study procedures or interpretation of study results

10. Patients receiving systemic steroid therapy or any other systemic immunosuppressive
medication at any dose level, as these may interfere with the mechanism of action of
study treatment. Local steroid therapies (eg, otic, ophthalmic, intra-articular, or
inhaled medications) are acceptable

11. History of adrenal insufficiency

12. History of interstitial lung disease

13. History of pneumonitis that required corticosteroid treatment or current pneumonitis

14. History of colitis or inflammatory bowel disease

15. Major surgery within 2 weeks of the first dose of study drug (minimally invasive
procedures such as bronchoscopy, tumor biopsy, insertion of a central venous access
device, and insertion of a feeding tube are not considered major surgery and are not
exclusionary)

16. Radiotherapy within 2 weeks of the first dose of study drug, with the exception of
palliative radiotherapy to a limited field, such as for the treatment of bone pain or
a focally painful tumor mass

17. Use of hematopoietic colony-stimulating growth factors (eg, G-CSF, GM-CSF, M-CSF) = 2
weeks prior to start of study drug. An erythroid-stimulating agent is allowed as long
as it was initiated at least 2 weeks prior to the first dose of study treatment and
the patient is not red blood cell transfusion dependent

18. Pregnant, likely to become pregnant, or lactating women (where pregnancy is defined as
the state of a female after conception and until the termination of gestation)

19. Women of childbearing potential who are sexually active with a non-sterilized male
partner, defined as all women physiologically capable of becoming pregnant, unless
they are using highly effective contraception during study treatment (defined in
Section 6.7), and must agree to continue using such precautions for 6 months after the
final dose of investigational product; cessation of birth control after this point
should be discussed with a responsible physician. Highly effective methods of
contraception are described in Section 6.7

20. Male patients must be surgically sterile or use double barrier contraception methods
from enrollment through treatment and for 6 months following administration of the
last dose of study drug

21. Patients who are in an institution due to official or judicial order.

22. Patients who are the investigator or any subinvestigator, research assistant,
pharmacist, study coordinator, or other staff thereof, directly involved in the
conduct of the study.

23. Contraindication for treatment with Investigator's Choice alternatives (dacarbazine,
ipilimumab and pembrolizumab) as per applicable labelling. Patient may have a
contraindication to 1 or 2 of the choices if he/she is a candidate for dosing with at
least 1 Investigator's Choice and meets all other study eligibility criteria.

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
Active, not recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
16/10/2017
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
1/06/2025
Actual
Sample size
Target
Accrual to date
Final
378
Recruitment in Australia
Recruitment state(s)
NSW,SA,VIC
Recruitment hospital [1] 0 0
Saint Vincents Hospital - Darlinghurst
Recruitment hospital [2] 0 0
Central Adelaide Local Health Network, Royal Adelaide Hospital Cancer Center - Adelaide
Recruitment hospital [3] 0 0
Peter MacCallum Cancer Center - Melbourne
Recruitment postcode(s) [1] 0 0
2010 - Darlinghurst
Recruitment postcode(s) [2] 0 0
5000 - Adelaide
Recruitment postcode(s) [3] 0 0
3000 - Melbourne
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
California
Country [2] 0 0
United States of America
State/province [2] 0 0
Colorado
Country [3] 0 0
United States of America
State/province [3] 0 0
Florida
Country [4] 0 0
United States of America
State/province [4] 0 0
Georgia
Country [5] 0 0
United States of America
State/province [5] 0 0
Illinois
Country [6] 0 0
United States of America
State/province [6] 0 0
Iowa
Country [7] 0 0
United States of America
State/province [7] 0 0
Massachusetts
Country [8] 0 0
United States of America
State/province [8] 0 0
Missouri
Country [9] 0 0
United States of America
State/province [9] 0 0
New York
Country [10] 0 0
United States of America
State/province [10] 0 0
North Carolina
Country [11] 0 0
United States of America
State/province [11] 0 0
Ohio
Country [12] 0 0
United States of America
State/province [12] 0 0
Oklahoma
Country [13] 0 0
United States of America
State/province [13] 0 0
Oregon
Country [14] 0 0
United States of America
State/province [14] 0 0
Pennsylvania
Country [15] 0 0
United States of America
State/province [15] 0 0
Texas
Country [16] 0 0
Belgium
State/province [16] 0 0
Bruxelles
Country [17] 0 0
Canada
State/province [17] 0 0
Alberta
Country [18] 0 0
Canada
State/province [18] 0 0
Toronto
Country [19] 0 0
France
State/province [19] 0 0
Nice
Country [20] 0 0
France
State/province [20] 0 0
Paris
Country [21] 0 0
Germany
State/province [21] 0 0
Nordrhein Westfalen
Country [22] 0 0
Germany
State/province [22] 0 0
Berlin
Country [23] 0 0
Germany
State/province [23] 0 0
Dresden
Country [24] 0 0
Germany
State/province [24] 0 0
Essen
Country [25] 0 0
Germany
State/province [25] 0 0
Hamburg
Country [26] 0 0
Germany
State/province [26] 0 0
Heidelberg
Country [27] 0 0
Germany
State/province [27] 0 0
Munich
Country [28] 0 0
Italy
State/province [28] 0 0
Milan
Country [29] 0 0
Italy
State/province [29] 0 0
Napoli
Country [30] 0 0
Netherlands
State/province [30] 0 0
Leiden
Country [31] 0 0
Poland
State/province [31] 0 0
Warsaw
Country [32] 0 0
Russian Federation
State/province [32] 0 0
Moscow
Country [33] 0 0
Russian Federation
State/province [33] 0 0
Saint Petersburg
Country [34] 0 0
Spain
State/province [34] 0 0
ES-Spain
Country [35] 0 0
Spain
State/province [35] 0 0
Sevilla
Country [36] 0 0
Switzerland
State/province [36] 0 0
Zürich
Country [37] 0 0
Ukraine
State/province [37] 0 0
Dnipropetrovs'k
Country [38] 0 0
Ukraine
State/province [38] 0 0
Kyiv
Country [39] 0 0
Ukraine
State/province [39] 0 0
Uzhhorod
Country [40] 0 0
United Kingdom
State/province [40] 0 0
Middlesex
Country [41] 0 0
United Kingdom
State/province [41] 0 0
Wirral
Country [42] 0 0
United Kingdom
State/province [42] 0 0
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/ct2/show/NCT03070392
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Immunocore Medical Information
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
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/ct2/show/NCT03070392