A Study of the Intra-Patient Escalation Dosing Regimen With IMCgp100 in Patients With Advanced Uveal Melanoma
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| ClinicalTrials.gov Identifier: NCT02570308 |
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Recruitment Status :
Active, not recruiting
First Posted : October 7, 2015
Last Update Posted : April 21, 2020
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Sponsor:
Immunocore Ltd
Information provided by (Responsible Party):
Immunocore Ltd
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Brief Summary:
IMCgp100-102 is a Phase I/II study of the weekly intra-patient escalation dose regimen with IMCgp100 as a single agent in patients with metastatic uveal melanoma (mUM). According to this regimen, all patients in the trial will receive 2 weekly doses of IMCgp100 at a dose level below the identified weekly recommended Phase II dose (RP2D-QW) and then a dose escalation will commence at the third weekly dose at C1D15. The Phase I testing of the intra-patient escalation dosing regimen is designed to achieve a higher exposure and maximal plasma concentration of IMCgp100 after doses at Cycle 1 Day 15 (C1D15) and thereafter .
| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Uveal Melanoma | Drug: IMCgp100 | Phase 1 Phase 2 |
This is a Phase I/II clinical study of IMCgp100 in patients with advanced uveal melanoma.
This is a Phase I/II study of IMCgp100 administered on a weekly basis with an intra-patient escalation dosing regimen. The intra-patient escalation occurs at the third weekly dose on Cycle 1 Day 15 (C1D15). According to this regimen, all patients in the trial will receive 2 weekly doses of IMCgp100 at a dose level below the identified weekly recommended Phase II dose (RP2D-QW) and then a dose escalation will commence at the third weekly dose at C1D15 with the goal to achieve a long-term dosing regimen at a dose higher than that identified for the straight weekly dosing regimen (RP2D-QW). The dose escalation will identify the intra-patient escalation regimen (RP2D-IE).
The Phase I portion of the study was a standard 3+3 dose escalation design. The Phase 1 portion of the study is now complete. The recommended Phase II dose of the intra-patient escalation dose regimen (RP2D-IE) was identified and the 2 expansion cohorts in metastatic uveal melanoma will be completed. The cohorts will enroll patients with metastatic uveal melanoma and are defined based on prior therapy The expansion portion will enroll approximately 150 patients.
| Study Type : | Interventional (Clinical Trial) |
| Estimated Enrollment : | 150 participants |
| Allocation: | Non-Randomized |
| Intervention Model: | Single Group Assignment |
| Masking: | None (Open Label) |
| Primary Purpose: | Treatment |
| Official Title: | A Phase I/II Open-label, Multi-center Study of the Safety and Efficacy of IMCgp100 Using the Intra-patient Escalation Dosing Regimen in Patients With Advanced Uveal Melanoma |
| Study Start Date : | February 2016 |
| Estimated Primary Completion Date : | October 30, 2020 |
| Estimated Study Completion Date : | January 29, 2021 |
Resource links provided by the National Library of Medicine
Genetics Home Reference related topics:
Melanoma
MedlinePlus related topics:
Melanoma
| Arm | Intervention/treatment |
|---|---|
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Experimental: Dose escalation
Dose escalation cohorts of the intra-patient escalation regimen. This arm is closed
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Drug: IMCgp100
Bispecific soluble HLA-A2 restricted gp100-specific TCR fused to anti-CD3 |
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Experimental: Dose expansion
Dose expansion cohort with the recommended phase 2 dose of the intra-patient dose escalation regimen
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Drug: IMCgp100
Bispecific soluble HLA-A2 restricted gp100-specific TCR fused to anti-CD3 |
Primary Outcome Measures :
- Phase 1 Recommended phase 2 dose of the intra-patient escalation regimen (RP2D-IE) [ Time Frame: 1 years ]
- 2. Phase 2: Objective response rate by RECIST 1.1 assessed by independent central review [ Time Frame: 2 years ]
Secondary Outcome Measures :
- Objective response rate (Phase 1) [ Time Frame: 2 years ]
- Progression free survival [ Time Frame: 2 years ]
- Overall survival [ Time Frame: 2 years ]
- Duration of response [ Time Frame: 2 years ]
- Time to response [ Time Frame: 2 years ]
- Minor response rate [ Time Frame: 2 years ]
- Number of treatment dose interruptions and reductions [ Time Frame: 2 years ]
- Area under the plasma concentration-time curve (AUC) [ Time Frame: 2 years ]
- Area under the plasma concentration-time curve (AUC) [ Time Frame: 3 weeks ]
- The maximum observed plasma drug concentration after single dose administration (Cmax) [ Time Frame: 2 years ]
- The time to reach maximum plasma concentration (Tmax) [ Time Frame: 3 weeks ]
- The elimination half-life (t1/2) [ Time Frame: 3 weeks ]
- Incidence of anti-IMCgp100 antibody formation [ Time Frame: 2 years ]
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| Ages Eligible for Study: | 18 Years and older (Adult, Older Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
Criteria
Inclusion Criteria:
- Male or female patients age ≥ 18 years of age at the time of informed consent
- Ability to provide and understand written informed consent prior to any study procedures
- Histologically or cytologically confirmed diagnosis of metastatic uveal melanoma (mUM)
- 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
- Life expectancy of >3 months as estimated by the investigator
- Human leukocyte antigen (HLA)-A*0201 positive
- ECOG Performance Status of 0 or 1 at Screening
- Patients in Phase 1 must have disease (measurable or non-measurable acceptable) according to Response Evaluation Criteria In Solid Tumors (RECIST) v.1.1 criteria
- Patients in Phase 2 must have measurable disease according to Response Evaluation Criteria In Solid Tumors (RECIST) v.1.1 criteria
- Patients in Phase 2 expansion cohort A will have experienced disease progression with 1 systemic treatment containing a checkpoint inhibitor. Any prior liver directed therapy is acceptable.
- Patients in Phase 2 expansion cohort B will have experienced disease progression with 1 or 2 prior lines of therapy, including up to 1 prior line of liver-directed therapy
Exclusion Criteria:
- 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
- History of severe hypersensitivity reactions to other biologic drugs or monoclonal antibodies
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Patient with any out-of-range laboratory values defined as:
- Serum creatinine > 1.5 x upper limit of normal (ULN) and/or creatinine clearance (calculated using Cockcroft-Gault formula, or measured) < 50 mL/min
- Total bilirubin > 1.5 x ULN, except for patients with Gilbert's syndrome who are excluded if total bilirubin > 3.0 x ULN or direct bilirubin > 1.5 x ULN
- ALT > 3 x ULN
- AST > 3 x ULN
- Absolute neutrophil count < 1.0 x 10^9/L
- Absolute lymphocyte count < 0.5 x 10^9/L (Phase 1 and Phase 2 Cohort A); absolute lymphocyte count < 1.0 x 10^9/L (Phase 2 Cohort B)
- Platelet count < 75 x 10^9/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
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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
- QTcF >470 msec on screening ECG or congenital long QT syndrome
- Acute myocardial infarction or unstable angina pectoris < 6 months prior to Screening
- Active infection requiring systemic antibiotic therapy. Patients requiring systemic antibiotics for infection must have completed therapy before Screening
- Known history of HIV infection. Testing for HIV status is not necessary unless clinically indicated or if required by local regulations
- 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
- 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
- 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
- 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
- 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 (eg, anti-CTLA-4), 4 weeks is indicated as washout period
- Presence of NCI CTCAE ≥ grade 2 toxicity (except alopecia, peripheral neuropathy and ototoxicity, which are excluded if ≥ NCI CTCAE grade 3) due to prior cancer therapy
- Chronic systemic corticosteroid use (ie, prednisone > 10 mg QD or the equivalent); treatment for well-controlled and asymptomatic adrenal insufficiency is permitted, but replacement dosing is limited to prednisone ≤ 10 mg QD or the equivalent, and patients must have no history of adrenal crisis. Local steroid therapies (eg, otic, ophthalmic, intra-articular or inhaled medications) are acceptable
- 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)
- 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
- Use of hematopoietic colony-stimulating growth factors (eg, G-CSF, GMCSF, M-CSF) ≤ 2 weeks prior to start of study drug. Patients must have completed therapy with any hematopoietic colony-stimulating factor at least 2 weeks before the first dose of study drug is given. 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
- 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)
- Patients with adrenal insufficiency or patients currently requiring chronic, systemic corticosteroid therapy at any dose for longer than 2 weeks. Local steroid therapies (eg, otic, ophthalmic, intraarticular, or inhaled medications) are acceptable
- Patients may not have been included in any prior IMCgp100 trial, regardless of treatment cohort
Information from the National Library of Medicine
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02570308
Locations
Show 26 study locations
Sponsors and Collaborators
Immunocore Ltd
| Responsible Party: | Immunocore Ltd |
| ClinicalTrials.gov Identifier: | NCT02570308 |
| Other Study ID Numbers: |
IMCgp100-102 |
| First Posted: | October 7, 2015 Key Record Dates |
| Last Update Posted: | April 21, 2020 |
| Last Verified: | April 2020 |
Additional relevant MeSH terms:
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Melanoma Uveal Neoplasms Neuroendocrine Tumors Neuroectodermal Tumors Neoplasms, Germ Cell and Embryonal Neoplasms by Histologic Type Neoplasms |
Neoplasms, Nerve Tissue Nevi and Melanomas Eye Neoplasms Neoplasms by Site Eye Diseases Uveal Diseases |