A Phase 1/2 Open-label, Multi-center Study of the Safety and Effectiveness of Increasing Doses of IMCgp100 in Patients with Advanced Uveal Melanoma
- Conditions
- Advanced Uveal MelanomaMedDRA version: 20.0Level: PTClassification code 10061252Term: Intraocular melanomaSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2015-004222-34-GB
- Lead Sponsor
- Immunocore Limited
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Authorised-recruitment may be ongoing or finished
- Sex
- All
- Target Recruitment
- 150
Patients eligible for inclusion in this study must meet all of the following 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
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 75
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 75
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 comple
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method