Clinical Trials Register

Summary
EudraCT Number:	2015-004222-34
Sponsor's Protocol Code Number:	IMCgp100-102
National Competent Authority:	Germany - PEI
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2018-01-29
Trial results	View results

Index
A. PROTOCOL INFORMATION
B. SPONSOR INFORMATION
C. APPLICANT IDENTIFICATION
D. IMP IDENTIFICATION
D.8 INFORMATION ON PLACEBO
E. GENERAL INFORMATION ON THE TRIAL
F. POPULATION OF TRIAL SUBJECTS
G. INVESTIGATOR NETWORKS TO BE INVOLVED IN THE TRIAL
N. REVIEW BY THE COMPETENT AUTHORITY OR ETHICS COMMITTEE IN THE COUNTRY CONCERNED
P. END OF TRIAL

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A. Protocol Information

A.1

Member State Concerned

Germany - PEI

A.2

EudraCT number

2015-004222-34

A.3

Full title of the trial

A Phase 1/2 Open-label, Multi-center Study of the Safety and Efficacy of IMCgp100 using the Intra-patient Escalation Dosing Regimen in Patients with Advanced Uveal Melanoma

A.3.1

Title of the trial for lay people, in easily understood, i.e. non-technical, language

A Phase I/II Open-label, Multi-center Study of the Safety and Effectiveness of Increasing Doses of IMCgp100 in Patients with Advanced Uveal Melanoma

A.4.1

Sponsor's protocol code number

IMCgp100-102

A.7

Trial is part of a Paediatric Investigation Plan

A.8

EMA Decision number of Paediatric Investigation Plan

B. Sponsor Information
B.Sponsor: 1
B.1.1	Name of Sponsor	Immunocore Limited
B.1.3.4	Country	United Kingdom
B.3.1 and B.3.2	Status of the sponsor	Commercial
B.4 Source(s) of Monetary or Material Support for the clinical trial:
B.4.1	Name of organisation providing support	Immunocore Limited
B.4.2	Country	United Kingdom
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Immunocore, Ltd.
B.5.2	Functional name of contact point	Mark Moyer
B.5.3	Address:
B.5.3.1	Street Address	92 Park Drive, Milton Park
B.5.3.2	Town/ city	Abingdon, Oxon
B.5.3.3	Post code	OX14 4RY
B.5.3.4	Country	United Kingdom
B.5.4	Telephone number	+441235438600
B.5.6	E-mail	mark.moyer@immunocore.com

D. IMP Identification
D.IMP: 1
D.1.2 and D.1.3	IMP Role	Test
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	No
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.2	Product code	IMCgp100
D.3.4	Pharmaceutical form	Concentrate for solution for infusion
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Intravenous use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.9.2	Current sponsor code	IMCgp100
D.3.9.3	Other descriptive name	IMCGP100
D.3.9.4	EV Substance Code	SUB66733
D.3.10	Strength
D.3.10.1	Concentration unit	mg/ml milligram(s)/millilitre
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	0.5
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	No
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	Yes
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	Yes
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	Yes
D.3.11.13.1	Other medicinal product type	Fusion protein

D.8 Information on Placebo

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

Advanced Uveal Melanoma

E.1.1.1

Medical condition in easily understood language

Cancer of the eye

E.1.1.2

Therapeutic area

Diseases [C] - Cancer [C04]

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	21.0
E.1.2	Level	PT
E.1.2	Classification code	10061252
E.1.2	Term	Intraocular melanoma
E.1.2	System Organ Class	10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)

E.1.3

Condition being studied is a rare disease

E.2 Objective of the trial

E.2.1

Main objective of the trial

Phase 1 dose escalation:
The primary objective is to identify the MTD and/or the RP2D of IMCgp100 in the intra-patient escalation dosing regimen (RP2D-IE).

Phase 2 dose expansion:
The primary objective is to estimate the objective response rate by independent central review (ICR) based on Response Evaluation Crtieria in Solid Tumors version 1.1 (RECISTv1.1) in patients with advanced UM who are treated with the RP2D-IE of IMCgp100.

E.2.2

Secondary objectives of the trial

• To characterize the safety and tolerability of IMCgp100 in the intra-patient dose escalation regimen
• To characterize the PK profile of single-agent IMCgp100 in the intra-patient dose escalation regimen
• To assess the anti-tumor efficacy of IMCgp100 with the parameters of objective response rate (Phase 1), overall survival, progression free survival (PFS), disease control rate (DCR), time to response, and the duration of response (DOR)
• To evaluate the incidence of anti-IMCgp100 antibody formation following multiple infusions of IMCgp100 in the intra-patient dose escalation regimen
• To determine the rate and duration of minor responses (defined as tumor response with a reduction in the sum of longest diameters of 10%–29%) and immune responses (as assessed by area under the tumor response curves [AUR])

E.2.3

Trial contains a sub-study

E.3

Principal 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 diagnosis of metastatic UM
4. Surgically sterile patients or patients of child-bearing potential who agree to use highly effective
methods of contraception during study dosing and for 6 months after last dose of study drug
5. Life expectancy of > 3 months as estimated by the investigator
6. HLA-A*0201 positive by central assay
7. ECOG Performance Status of 0 or 1 at Screening
8. Patients must have disease (measurable or non-measurable acceptable) according to RECIST v.1.1
criteria in Phase 1 dose escalation cohorts. Patients must have measurable disease in the Phase 2
dose expansion cohorts
9. Phase 1 dose escalation cohorts only: any prior therapy is acceptable
Prior therapy in Phase 2 expansion cohorts:
 Cohort A: Patients will have experienced disease progression with 1 systemic treatment
regimen containing a checkpoint inhibitor, including either a CTLA4 inhibitor (ipilimumab or
tremelimumab) and/or a PD-1/PD-L1 inhibitor. Any prior LDT is acceptable in this cohort
 Cohort B: Patients will have experienced disease progression with 1 or 2 prior lines of therapy in the metastatic or advanced setting including chemotherapy, immunotherapy or targeted therapy. Only a single line of local, LDT including chemotherapy, radiotherapy, radiofrequency ablation or embolization is allowed. A line of LDT is defined as one modality of treatment that is administered until completion of treatment or disease progression. For patients who have received prior LDT, this will count as a line of therapy. Prior surgical resection of oligometastatic liver disease is allowed and is not counted as a line of LDT. A patient may have discontinued systemic therapy prior to disease progression if the patient experienced an adverse reaction that required treatment discontinuation, as per Investigator’s judgment and applicable labelling. Prior checkpoint inhibitor therapy is acceptable but not required in this cohort.
a. This means patients with the following treatments are eligible under Cohort B:
o 1 systemic therapy and 1 LDT
o 1 – 2 systemic therapies and 0 LDT
o 0 systemic therapy and 1 LDT
b. Adjuvant therapies and local therapies for treatment of disease outside of the liver do not count towards the lines of prior therapy.
10. 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

E.4

Principal exclusion criteria

Patients eligible for this study must not meet any of the following criteria:
1. 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. Asymptomatic and adequately treated CNS metastases are not exclusionary
2. History of severe hypersensitivity reactions to other biologic drugs or monoclonal antibodies
3. Patient with any out-of-range laboratory values 
4. Dose escalation only: Presence of high tumor burden, defined as liver replacement of > 60% hepatic organ volume with tumor
5. Clinically significant cardiac disease or impaired cardiac function, including any of the following:
 Clinically significant and/or uncontrolled heart disease such as congestive heart failure (New York Heart Association grade ≥ 2), uncontrolled hypertension, or clinically significant arrhythmia currently requiring medical treatment
 QTc > 470 msec on screening electrocardiogram (ECG) or congenital long QT syndrome
 Acute myocardial infarction or unstable angina pectoris < 6 months prior to Screening
6. Active infection requiring systemic antibiotic therapy. Patients requiring systemic antibiotics for infection must have completed therapy before Screening
7. Known history of human immunodeficiency virus (HIV) infection. Testing for HIV status is not necessary unless clinically indicated or if required by local regulations
8. 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 or if required by local regulations
9. Patients receiving systemic treatment with systemic steroid therapy or any other immunosuppressive medication at any dose level that would interfere with the action of the study drugs in the opinion of the investigator
10. 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
11. Any medical condition that would, in the investigator’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
12. Systemic anti-cancer therapy within 2 weeks of the first dose of study treatment. For cytotoxic or immunotherapy agents that can present with major delayed toxicity, 4 weeks is indicated as washout period
13. Presence of NCI CTCAE ≥ grade 2 toxicity due to prior cancer therapy
14. Patients with adrenal insufficiency or patients currently requiring chronic, systemic corticosteroid therapy at any dose for longer than 2 weeks. Local steroid therapies are acceptable
15. Major surgery within 2 weeks of the first dose of study drug 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 (e.g., G-CSF, GMCSF, M-CSF) ≤ 2 weeks prior to start of study drug. Patients must have completed therapy with hematopoietic colonystimulating factor at least 2 weeks before the first dose of study drug is given. An erythroidstimulating 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 child-bearing 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, 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. 20. Male patients must be surgically sterile or use double barrier contraception method from enrollment through treatment and for 6 months following administration of the last dose of study drug
21. Patients may not have been included in any prior IMCgp100 trial, regardless of assigned treatment cohort

E.5 End points

E.5.1

Primary end point(s)

Phase 1 dose escalation: The primary endpoint is incidence of DLT

Phase 2 dose escalation: The primary endpoint is ORR by RECISTv1.1 assessed by ICR.

E.5.1.1

Timepoint(s) of evaluation of this end point

The DLT observation period for the Phase I cohorts will be the first cycle during IMCgp100 dosing (C1D1 until C1D28).

ORR is defined as the proportion of patients with measurable disease with at least 1 visit response of CR or PR that is confirmed at least 4 weeks later, as defined in RECIST v.1.1.

E.5.2

Secondary end point(s)

• Tolerability: Dose interruptions, reductions, and dose intensity of all administered agents
• Serum PK parameters (eg, AUC, Cmax, T, t1/2)
• Tumor response endpoints (ORR [Phase 1], PFS, DCR, DOR, time to response) as determined by RECIST v.1.1
o Note: For the Phase 2 expansion cohorts, primary assessment of tumor-based endpoints will be provided by an ICR. Investigator assessment data will also be collected for both Phase 1 dose escalation cohort (primary assessment) and Phase 2 expansion cohorts (secondary assessment)
• OS
• Assessments of anti-IMCgp100 antibody formation
• Minor tumor responses (10% to 29% reduction in the SLD) and immune responsed (as assessed by AUC)

E.5.2.1

Timepoint(s) of evaluation of this end point

AEs/SAEs, tolerability: From baseline at each study visit until follow-up.

PK: samples taken pre- and post- dose. Extended PK sampling will be done at C1D1 and C1D15 dosing.

Tumor assessments will be performed at the following time points:
• Screening
• Every 8 weeks ± 1 week from C3D1 to C11D1, then every 3 cycles until PD per irRC or patient withdrawal. After EOT, during PD follow up, every 8 weeks until 40 weeks, then every 12 weeks until PD per irRC, or lost to follow-up
• Partial response (PR) or complete response (CR), per both RECIST v.1.1 and irRC, will be confirmed by a new assessment after at least 4 weeks. Also PD, as per irRC, needs to be confirmed after at least 4 weeks
• At EOT, if a scan was not conducted within 30 days prior to EOT

E.6 and E.7 Scope of the trial

E.6

Scope of the trial

E.6.1

Diagnosis

E.6.2

Prophylaxis

E.6.3

Therapy

E.6.4

Safety

Yes

E.6.5

Efficacy

Yes

E.6.6

Pharmacokinetic

Yes

E.6.7

Pharmacodynamic

Yes

E.6.8

Bioequivalence

E.6.9

Dose response

E.6.10

Pharmacogenetic

E.6.11

Pharmacogenomic

E.6.12

Pharmacoeconomic

E.6.13

Others

E.7

Trial type and phase

E.7.1

Human pharmacology (Phase I)

Yes

E.7.1.1

First administration to humans

E.7.1.2

Bioequivalence study

E.7.1.3

Other

Yes

E.7.1.3.1

Other trial type description

MTD

E.7.2

Therapeutic exploratory (Phase II)

Yes

E.7.3

Therapeutic confirmatory (Phase III)

E.7.4

Therapeutic use (Phase IV)

E.8 Design of the trial

E.8.1

Controlled

E.8.1.1

Randomised

E.8.1.2

Open

Yes

E.8.1.3

Single blind