Safety and efficacy of IMCgp100 versus Investigator’s Choice in advanced uveal melanoma

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Immunocore Limited

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

19 Dec 2017 → 18 Sep 2025

Decision date (initial)

2024-11-07

Transition trial

Yes

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

Yes

External identifiers

EU CT number

2024-517290-24-00

EudraCT number

2015-003153-18

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Pharmacodynamic, Efficacy, Safety, Pharmacokinetic, Therapy

The dual primary objectives are:

1. To compare the OS in all patients randomized to the tebentafusp monotherapy versus all patients randomized to the Investigator’s Choice monotherapy

2. To compare the OS in all patients randomized to the tebentafusp monotherapy who develop a rash within the first week of treatment versus all patients randomized to the Investigator’s Choice monotherapy

Both objectives relate to HLA-A*0201 positive patients with
advanced UM with no prior treatment in the metastatic setting.

Secondary objectives 5

1. To characterize the safety and tolerability of single-agent tebentafusp in the intra-patient dose escalation regimen relative to Investigator’s Choice
2. To characterize the PK profile of single-agent tebentafusp in the intra-patient dose escalation regimen Serum PK parameters (eg, Cmax, Cmin, Ctrough)
3. To assess the anti-tumor efficacy of tebentafusp versus Investigator’s Choice with the parameters of PFS, BOR, DOR, time to response, and DCR using RECIST v1.1
4. To evaluate the treatment and disease impact to HRQoL in patients treated with tebentafusp versus patients treated with Investigator’s Choice. HRQoL will be assessed by the EQ-5D,5L and the EORTC QLQ-C30
5. To evaluate the incidence of anti-tebentafusp antibody formation following multiple infusions of tebentafusp in the intra-patient dose escalation regimen

Conditions and MedDRA coding

Previously untreated advanced uveal melanoma (UM)

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 9

1. Patients 18 years of age or older
2. Ability to provide and understand written informed consent
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.
5. HLA-A*0201 positive
6. Life expectancy of > 3 months
7. ECOG Performance Status of 0 or 1
8. Patients have measurable disease or non-measurable disease according to RECIST v1.1
9. All other relevant medical conditions must be well-managed and stable

Exclusion criteria 23

1. Patient with any out-of-range laboratory values defined as: • Serum creatinine > 1.5 × upper limit of normal (ULN) and/or creatinine clearance (calculated using Cockcroft-Gault formula, or measured) < 50 mL/minute • Total bilirubin > 1.5 × ULN, except for patients with Gilbert’s syndrome who are excluded if total bilirubin > 3.0 × ULN or direct bilirubin > 1.5 × ULN • Alanine aminotransferase > 3 × ULN • Aspartate aminotransferase > 3 × ULN • Absolute neutrophil count < 1.0 × 109/L • Absolute lymphocyte count < 0.5 × 109/L • Platelet count < 75 × 109/L • Hemoglobin < 8 g/dL
2. History of severe hypersensitivity reactions (eg, anaphylaxis) to other biologic drugs or monoclonal antibodies
3. 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, uncontrolled hypertension, or clinically significant arrhythmia currently requiring medical treatment • QTcF > 470 msec on screening electrocardiogram (ECG) or congenital long QT syndrome. • Acute myocardial infarction or unstable angina pectoris
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 per institutional protocol.
8. Malignant disease, other than that being treated in this study.
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.
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
16. Radiotherapy within 2 weeks of the first dose of study drug
17. Use of hematopoietic colony-stimulating growth factors (eg, G-CSF, GM-CSF, M-CSF) ≤ 2 weeks prior to start of study drug.
18. Pregnant, or lactating
19. Women of childbearing potential, unless they are using highly effective contraception during study treatment.
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 related to the investigator or any sub-investigator, 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.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Overall survival, date of death in relation to study randomization

Secondary endpoints 5

1. Safety and tolerability: Incidence and severity of AEs and SAEs; changes in safety laboratory parameters, vital signs, and electrocardiogram (QTcF); dose interruptions, reductions, discontinuations, and dose intensity of all administered agents
2. Serum PK parameters (eg, Cmax, Cmin, Ctrough)
3. • PFS • BOR • DOR • Time to response DCR (defined as CR or PR, or SD ≥ 24 weeks)
4. EQ-5D,5L and EORTC QLQ-C30 change from Baseline over time and between treatment strategies
5. Assessments of anti-tebentafusp antibody formation

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Comparator 3

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Immunocore Limited

Sponsor organisation

Immunocore Limited

Address

92 Park Drive, Milton Milton

City

Abingdon

Postcode

OX14 4RY

Country

United Kingdom

Scientific contact point

Organisation

Immunocore Limited

Contact name

Regulatory Affairs

Public contact point

Organisation

Immunocore Limited

Contact name

Information Desk

Third parties 19

Locations

5 EU/EEA countries · 6 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 44 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

3 submissions — initial application plus substantial / non-substantial modifications