Advanced Uveal Melanoma MedDRA version: 20.0 Level: PT Classification code 10061252 Term: Intraocular melanoma System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Interventions
Product Code: IMCgp100
Pharmaceutical Form: Concentrate for solution for infusion
Current Sponsor code: IMCgp100
Other descriptive name: IMCGP100
Concentration unit: mg/ml milligram(s)/millilitre
Conc
Sponsors
Immunocore Limited
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 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
Exclusion criteria
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 comple
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Phase 1 Dose Escalation: The primary objective is to identify the MTD and/or the RP2D of IMCgp100 in the intra-patient dose escalation 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 Criteria in Solid Tumors version 1.1 RECISTv1.1) in patients with advanced UM who are treated with the RP2D-IE of IMCgp100.;Secondary Objective: • 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 [AUC]);Primary end point(s): Phase 1 dose escalation: The primary endpoint is incidence of DLT. Phase 2 dose expansion: The primary endpoint is ORR by RECISTv.1.1 assessed by ICR.;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. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): - Tolerability: Dose interruptions, reductions, and dose intensity of all administered agents - Serum PK parameters (e.g., 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 responses (as assessed by AUC);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 | — |
Countries
Canada, Germany, Spain, United Kingdom, United States
Contacts
Public ContactLisa Cooper
Immunocore Ltd.
Outcome results
None listed