A Phase II Randomized, Open-label, Multi-center Study of the Safety and Efficacy of IMCgp100 Compared with Investigator*s Choice in HLA-A*0201 Positive Patients with Previously Untreated Advanced Uveal Melanoma
- Conditions
- eye melanoma and eye cancer10030054
- Registration Number
- NL-OMON48897
- Lead Sponsor
- Immunocore Limited
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Completed
- Sex
- Not specified
- Target Recruitment
- 5
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 local, liver-directed therapy including chemotherapy, radiotherapy, radiofrequency ablation (RFA), or embolization
• Prior surgical resection of oligometastatic liver 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
5. HLA-A*0201 positive by central assay
6. Life expectancy of > 3 months as estimated by the investigator
7. Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1 at Screening
8. Patients must have measurable disease according to RECIST v.1.1
9. 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
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 < 1.0 × 109/L
• Platelet count < 75 × 109/L
• Hemoglobin < 8 g/dL
• Potassium, magnesium, corrected calcium or phosphate abnormality of National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) grade > 1
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 (New York Heart Association grade >= 2), uncontrolled hypertension or clinically significant arrhythmia
currently requiring medical treatment
• QT interval corrected by Friderica's formula > 470 msec on screening electrocardiogram (ECG) or congenital long QT syndrome
• Acute myocardial infarction or unstable angina pectoris < 6 months prior to Screening
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 disease progression 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. His
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method <p>Efficacy assessments:<br /><br>Radiologic assessments should be performed as scheduled every 12 weeks (Section<br /><br>7.3.1), using a reference to C1D1 and should NOT follow delays incurred in the<br /><br>treatment period.<br /><br>Tumor response will be determined locally according to 2 sets of criteria:<br /><br>1. RECIST v.1.1<br /><br>2. Modified irRECIST<br /><br>The blinded independent central review (BICR) assessment will be used for the<br /><br>analysis of response according to RECIST v.1.1 and irRECIST for efficacy<br /><br>endpoints of the study. Local investigator*s review of the imaging studies<br /><br>will be used for treatment decision making (study discontinuation due to<br /><br>progressive disease as per irRECIST or RECIST v1.1).</p><br>
- Secondary Outcome Measures
Name Time Method <p>Safety assessments:<br /><br>Safety will be monitored by assessing physical examination, vital signs, body<br /><br>height and weight, performance status, hematology, chemistry,<br /><br>coagulation, urinalysis, thyroid function, pregnancy, ECG, cytokine testing, as<br /><br>well as collecting of the AEs at every visit. All data (including efficacy and<br /><br>safety data) will be reviewed centrally by the independent data monitoring<br /><br>committee.<br /><br><br /><br>Other assessments:<br /><br>- Patient reported outcomes will be assessed using, (1) the generalhealth<br /><br>status EQ-5D questionnaires and (2) the HRQoL instrumentEORTC QLQ-C30<br /><br>- Serum PK parameters and immunogenicity in IMCgp100 Arm 1 only<br /><br>- Pharmacodynamic assessment on pre- and post-treatment newly obtained tumor<br /><br>samples<br /><br>- Treatment and health-related medical resource utilization </p><br>