Safety and Efficacy of IMCgp100 Versus Investigator Choice in Advanced Uveal Melanoma

Uveal Melanoma Clinical Trial

Official 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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT03070392
• Other study ID #: IMCgp100-202
• Status: Active, not recruiting
• Phase: Phase 2
• Start date: October 16, 2017
• Est. completion date: June 2025

Study information

• Verified date: March 2024
• Source: Immunocore Ltd
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Description:

This Phase II study is designed to evaluate the safety and efficacy of IMCgp100 compared with Investigator's Choice (dacarbazine, ipilimumab or pembrolizumab) in HLA-A*0201 positive adult patients with advanced UM treated in the first line setting with no prior systemic or liver-directed chemo-, radio- or immune-therapy administered in the advanced setting (prior surgical resection of liver metastases and adjuvant systemic therapy are acceptable). Comparison of the IMCgp100 efficacy results in this Phase II study will be made with the concurrently randomized arm (Investigator's Choice) with a primary endpoint of overall survival (OS) and secondary efficacy endpoints of progression-free survival (PFS), objective response rate (ORR), duration of response (DOR), and disease control rate (DCR).

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 378
• Est. completion date: June 2025
• Est. primary completion date: October 13, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 99 Years

Eligibility

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

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.

Related Conditions & MeSH terms

• Melanoma
• Uveal Melanoma
• Uveal Neoplasms

Intervention

Biological:
• 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

Drug:
• 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

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

Locations

Country	Name	City	State
Australia	Central Adelaide Local Health Network, Royal Adelaide Hospital Cancer Center	Adelaide	South Australia
Australia	Saint Vincents Hospital	Darlinghurst	New South Wales
Australia	Peter MacCallum Cancer Center	Melbourne	Victoria
Belgium	Institut Roi Albert II Cliniques Universitaires St-Luc	Bruxelles
Canada	Cross Cancer Institute	Edmonton	Alberta
Canada	Princess Margaret Cancer Centre	Toronto
France	Centre Atoine Lacassagne	Nice
France	Institut Curie	Paris
Germany	Charite - Campus Benjamin Franklin	Berlin
Germany	Universitätsklinikum Carl Gustav Carus	Dresden
Germany	University Hospital Essen	Essen
Germany	University of Hamburg	Hamburg
Germany	Nationales Centrum für Tumorerkrankungen	Heidelberg
Germany	Universitaetsklinikum Koeln Dermatologie und Venerologie	Koeln	Nordrhein Westfalen
Germany	Klinik und Poliklinik für Dermatologie und Allergologie	Munich
Italy	Fondazione ICCRS	Milan
Italy	Istituto Nazionale Tumori - IRCCS Fondazione "G. Pascale" - UOC Melanoma, Immunoterapia Oncologica e Terapie Innovative	Napoli
Netherlands	LUMC Medical Oncology	Leiden
Poland	Centrum Onkologii - Instytut im. Marii Sklodowskiej-Curie	Warsaw
Russian Federation	Federal State Budgetary Institution N.N. Blokhin National Medical Research Center of Oncology	Moscow
Russian Federation	Federal State Budget Institution National Medical Research Center of Oncology	Saint Petersburg
Spain	Institut Catala d'Oncologia (ICO) - L'Hospitalet	L'Hospitalet De Llobregat	ES-Spain
Spain	Hospital Universitario La Paz	Madrid	ES-Spain
Spain	Hospital Clínico Universitario de Santiago de Compostela	Santiago De Compostela	ES-Spain
Spain	Hospital Universitario Virgen Macarena	Sevilla
Spain	Hospital Universitario General de Valencia	Valencia	ES-Spain
Switzerland	University of Zurich Hospital	Zürich
Ukraine	Dnipropetrovsk State Medical Academy	Dnipropetrovs'k
Ukraine	Kyiv Munitipal Hospital	Kyiv
Ukraine	Uzhhorod Central City Clinical Hospital	Uzhhorod
United Kingdom	The Clatterbridge Cancer Centre	Bebington	Wirral
United Kingdom	Beatson West of Scotland Cancer Centre	Glasgow
United Kingdom	Mount Vernon Cancer Centre	Northwood	Middlesex
United States	Winship Cancer Institute of Emory University	Atlanta	Georgia
United States	University of Colorado	Aurora	Colorado
United States	Dana Farber Cancer Institute	Boston	Massachusetts
United States	Massachusetts General Hospital	Boston	Massachusetts
United States	Roswell Park Cancer Institute	Buffalo	New York
United States	Northwestern University	Chicago	Illinois
United States	The University of Chicago Medicine	Chicago	Illinois
United States	The Ohio State University	Columbus	Ohio
United States	Duke University Health System	Durham	North Carolina
United States	Houston Methodist Cancer Center	Houston	Texas
United States	University of Iowa	Iowa City	Iowa
United States	The Angeles Clinic and Research Institute	Los Angeles	California
United States	UCLA Medical Center	Los Angeles	California
United States	University of Miami - Sylvester Comprehensive Cancer Center	Miami	Florida
United States	Columbia University Medical Center	New York	New York
United States	Memorial Sloan Kettering Cancer Center	New York	New York
United States	University of Oklahoma	Oklahoma City	Oklahoma
United States	Byers Eye Institute, Stanford University	Palo Alto	California
United States	Thomas Jefferson University Hospital	Philadelphia	Pennsylvania
United States	University of Pittsburgh Medical Center	Pittsburgh	Pennsylvania
United States	Portland Providence Medial Center	Portland	Oregon
United States	Washington University School of Medicine	Saint Louis	Missouri
United States	California Pacific Medical Center	San Francisco	California

Sponsors (1)

Lead Sponsor	Collaborator
Immunocore Ltd

Countries where clinical trial is conducted

United States,  Australia,  Belgium,  Canada,  France,  Germany,  Italy,  Netherlands,  Poland,  Russian Federation,  Spain,  Switzerland,  Ukraine,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Efficacy: Overall Survival	Overall survival is defined as the time from randomization to date of death due to any cause.	From randomization to the data cut off date of 13-Oct-2020; median follow-up duration was 14.1 months.
Secondary	Safety: Number of Participants With Treatment Emergent Adverse Events	Safety was defined as the number of participants with treatment emergent adverse events, including laboratory abnormalities, ECG changes, and/or physical examination findings.	Safety was assessed from informed consent through 90 days after end of treatment, up to 36 months.
Secondary	Efficacy: Progression Free Survival (PFS)	Progression free survival (PFS) is defined as the time from randomization to the date of progression (RECIST v1.1) or death due to any cause.	PFS was assessed every 3 months from randomization until disease progression or death, up to 36 months.
Secondary	Quality-of-Life: Change From Baseline in EQ-5D,5L Domain Scores	General health status was assessed using the EQ-5D,5L questionnaire, which includes five dimensions (5D): mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. Each dimension has 3 scoring levels, where 1 indicates a better health state (no problems) and 3 indicates a worse health state. A positive change indicates improvement.	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	Quality-of-life: Change From Baseline in EQ-5D Visual Analogue Score (VAS)	The EQ-5D VAS score records the participant's self-rated health on a vertical visual analogue scale, with 0 being the worst imaginable health state and 100 being the best imaginable health state. A positive change indicates improvement.	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	Quality-of-Life: Change From Baseline in EORTC QLQ-C30 Global Health Status	Global health status and quality of life was assessed using the EORTC QLQ-C30 questionnaire. The score range for the EORTC QLQ-C30 is from 0 to 100, with higher scores indicating better functioning and better global health status and health-related quality of life. A positive change indicates improvement.	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	Pharmacokinetics (PK): Tebentafusp Concentration	Serum PK concentrations of tebentafusp were collected over time.	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	Efficacy: Objective Response Rate (ORR)	Objective response rate (ORR) is defined as the proportion of patients achieving an objective response (RECIST v1.1).	ORR will be assessed after every participant has had at least 3 assessments, conducted every 3 months, up to 5.5 years.
Secondary	Efficacy: Duration of Response (DOR)	Duration of response (DOR) is defined as the time from first documented objective response (RECIST v1.1) until the date of documented disease progression.	DOR will be assessed every 3 months from randomization until disease progression, assessed up to 5.5 years.
Secondary	Efficacy: Disease Control Rate (DCR)	Disease control rate (DCR) is defined as the proportion of patients with either an objective response or stable disease (RECIST v1.1)	DCR will be assessed every 3 months from randomization until disease progression, up to 5.5 years.
Secondary	Pharmacokinetics: Frequency of Anti-IMCgp100 Antibody Formation		Approximately 5 assessments will be performed between first dose of IMCgp100 and end of treatment, assessed up to 5.5 years.