Back to resultsA Study of the Intra-Patient Escalation Dosing Regimen With IMCgp100 in Patients With Advanced Uveal Melanoma
Primary Purpose
Uveal Melanoma
Status
Completed
Phase
Phase 1
Locations
International
Study Type
Interventional
Intervention
IMCgp100
Sponsored by
About this trial
This is an interventional treatment trial for Uveal Melanoma focused on measuring Tebentafusp, IMCgp100, gp100, metastatic melanoma, ImmTAC, Immunotherapy, Bispecific T cell receptor fusion protein, Immune mobilizing monoclonal T cell receptor, against cancer, UM, mUM, Kimmtrak
Eligibility Criteria
Inclusion Criteria:
- Male or female participants 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 participants or participants 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.
- Human leukocyte antigen (HLA)-A*0201 positive.
- ECOG Performance Status of 0 or 1 at Screening.
- Phase 2 will include participants with previously treated uveal melanoma in the metastatic setting.
Exclusion Criteria:
- Presence of symptomatic or untreated central nervous system (CNS) metastases, or CNS metastases that require doses of corticosteroids.
- History of severe hypersensitivity reactions to other biologic drugs or monoclonal antibodies.
- Participants with any out-of-range laboratory values.
- Clinically significant cardiac disease or impaired cardiac function.
- Active infection requiring systemic antibiotic therapy.
- Known history of HIV infection.
- Active hepatitis B virus (HBV) or hepatitis C virus (HCV) infection per institutional protocol.
- Participants 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.
- Any medical condition that would, in the investigator's judgment, prevent participation in the clinical study due to safety concerns, compliance with clinical study procedures or interpretation of study results.
- 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.
- Pregnant, likely to become pregnant, or lactating women.
Sites / Locations
- University California, San Diego Moores Cancer Center
- The Angeles Clinic and Research Institute - W LA Office
- California Pacific Medical Center
- University of Colorado Denver Anschutz Medical Campus
- Georgetown University - Lombardi Comprehensive Cancer Center
- University of Miami Hospital Clinics/Sylvester Comprehensive Cancer Center
- H. Lee Moffitt Cancer Center and Research Institute, Inc
- The University of Chicago Medical Center
- Washington University, School of Medicine
- Roswell Park Cancer Institute
- Columbia University Medical Center - The New York Presbyterian Hospital
- Memorial Sloan Kettering Hospital
- Dean A. Mcgee Eye Institute
- Providence Portland Medical Center
- Thomas Jefferson University Medical Oncology Clinic
- Vanderbilt University Medical Center
- Baylor Scott & White Health
- Princess Margaret Cancer Center
- Universitaetsklinikum Heidelberg
- Charite Universitaetsmedizin Berlin - Campus Benjamin Franklin
- ICO l'Hospitalet - Hospital Duran i Reynals
- Hospital Universitario La Paz
- Hospital Universitario Virgen Macarena
- Hospital General Universitario de Valencia
- The Clatterbridge Cancer Centre
- Mount Vernon Cancer Centre
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Experimental
Arm Label
Dose escalation
Dose expansion
Arm Description
Dose escalation cohorts of the intra-patient escalation regimen.
Dose expansion cohort with the recommended phase 2 dose of the intra-patient dose escalation regimen.
Outcomes
Primary Outcome Measures
Number of Participants With a Dose Limiting Toxicity (DLT) in Phase 1
Number of participants with a dose limiting toxicity, defined as an adverse event (AE) or abnormal laboratory value assessed as having a suspected relationship to study drug, and unrelated to disease, disease progression, inter-current illness, or concomitant medications that occurs within the first cycle of treatment and meets any of the pre-specified criteria.
Objective Response Rate in Phase 2
Objective response rate (ORR) is defined as the percentage of participants with measurable disease with at least 1 visit response of complete response (CR) or partial response (PR) that is confirmed at least 4 weeks later, as defined in RECIST v.1.1 and assessed by an independent central review (ICR). The denominator in the calculation of the ORR is the number of participants in the full analysis set with measurable disease at baseline.
Secondary Outcome Measures
Objective Response Rate in Phase 1
ORR is defined as the percentage of participants 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 and assessed by an investigator. The denominator in the calculation of the ORR is the number of participants in the full analysis set with measurable disease at baseline.
Progression-free Survival
Progression-free survival is defined as the time in months from first dose of study drug until the date of disease progression or death (by any cause in the absence of disease progression) as assessed by RECIST v1.1 by the investigator for Phase 1 and ICR for Phase 2.
Disease Control Rate
Disease control rate (DCR) is defined as the percentage of participants with a best overall response of CR or PR or stable disease (SD) recorded at least 24 weeks (± 1 week) after commencement of study drug and prior to any progressive disease (PD) event, as assessed by RECIST v1.1 by the investigator for Phase 1 and ICR for Phase 2.
Duration of Response
Duration of response (DOR) is defined as the time in months from the date of first documented objective response (CR or PR) until the date of documented disease progression or death by any cause in the absence of disease progression as assessed by RECIST v1.1 by the investigator for Phase 1 and ICR for Phase 2.
Time to Response
Time to response (TTR) is defined as the time in months from the date of first dose of study drug until the date of first documented objective response as assessed by RECIST v1.1 by the investigator for Phase 1 and ICR for Phase 2.
Overall Survival
Overall survival (OS) is defined as the time in months from the date of first dose of study drug until death due to any cause in general.
Minor Response Rate
Rate of minor response (or better) is defined as the proportion of participants with a confirmed CR, PR, or minor response (MinR) as assessed by RECIST v1.1 by the investigator for Phase 1 or ICR for Phase 2, where MinR is a reduction from baseline in sum of diameters between 10%-29%. The sum of diameters is defined as per RECIST v1.1 as the sum of longest diameters or short axis of target lesions (mm).
Number of Participants With Treatment Dose Interruptions or Reductions
Tolerability of study treatment was assessed by summarizing the number of participants with dose interruptions or reductions that occurred during the treatment period.
Area Under the Plasma Concentration-Time Curve (AUC) of Tebentafusp
The AUC was determined in in dose escalation cohorts.
Maximum Plasma Concentration (Cmax) of Tebentafusp
The Cmax is determined in dose escalation cohorts.
Time to Maximum Plasma Concentration (Tmax) of Tebentafusp
The Tmax of tebentafusp is determined in dose escalation cohorts.
Apparent Terminal Plasma Half-life (t½) of Tebentafusp
The t½ of tebentafusp is reported in dose escalation cohorts.
Percentage of Participants With Anti-IMCgp100 Antibody Formation
Overall antidrug antibody (ADA) is presented as number of ADA-positive participants relative to total number of participants with evaluable ADA results in each cohort
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT02570308
Brief Title
A Study of the Intra-Patient Escalation Dosing Regimen With IMCgp100 in Patients With Advanced Uveal Melanoma
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 Type
Interventional
2. Study Status
Record Verification Date
February 2023
Overall Recruitment Status
Completed
Study Start Date
February 29, 2016 (Actual)
Primary Completion Date
March 20, 2020 (Actual)
Study Completion Date
October 17, 2022 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Immunocore Ltd
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Data Monitoring Committee
No
5. Study Description
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 participants with metastatic uveal melanoma (mUM). According to this regimen, all participants in the trial received 2 weekly doses of IMCgp100 at a dose level below the identified weekly recommended Phase II dose (RP2D-QW) and then a dose escalation commenced 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.
Detailed Description
This is a Phase I/II clinical study of IMCgp100 in participants 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 occurred at the third weekly dose on Cycle 1 Day 15 (C1D15). According to this regimen, all participants in the trial received 2 weekly doses of IMCgp100 at a dose level below the identified weekly recommended Phase II dose (RP2D-QW), and then a dose escalation commenced 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 weekly dosing regimen (RP2D-QW). The dose escalation identified the intra-patient escalation regimen (RP2D-IE).
The Phase I portion of the study was a standard 3+3 dose escalation design.The recommended Phase II dose of the intra-patient escalation dose regimen (RP2D-IE) was identified and expansion cohorts in metastatic uveal melanoma was accrued based on prior therapy.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Uveal Melanoma
Keywords
Tebentafusp, IMCgp100, gp100, metastatic melanoma, ImmTAC, Immunotherapy, Bispecific T cell receptor fusion protein, Immune mobilizing monoclonal T cell receptor, against cancer, UM, mUM, Kimmtrak
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
146 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Dose escalation
Arm Type
Experimental
Arm Description
Dose escalation cohorts of the intra-patient escalation regimen.
Arm Title
Dose expansion
Arm Type
Experimental
Arm Description
Dose expansion cohort with the recommended phase 2 dose of the intra-patient dose escalation regimen.
Intervention Type
Drug
Intervention Name(s)
IMCgp100
Other Intervention Name(s)
Tebentafusp, Kimmtrak
Intervention Description
Bispecific soluble HLA-A2 restricted gp100-specific T-cell receptor fused to anti-CD3
Primary Outcome Measure Information:
Title
Number of Participants With a Dose Limiting Toxicity (DLT) in Phase 1
Description
Number of participants with a dose limiting toxicity, defined as an adverse event (AE) or abnormal laboratory value assessed as having a suspected relationship to study drug, and unrelated to disease, disease progression, inter-current illness, or concomitant medications that occurs within the first cycle of treatment and meets any of the pre-specified criteria.
Time Frame
Up to 49 months
Title
Objective Response Rate in Phase 2
Description
Objective response rate (ORR) is defined as the percentage of participants with measurable disease with at least 1 visit response of complete response (CR) or partial response (PR) that is confirmed at least 4 weeks later, as defined in RECIST v.1.1 and assessed by an independent central review (ICR). The denominator in the calculation of the ORR is the number of participants in the full analysis set with measurable disease at baseline.
Time Frame
Up to 38 months
Secondary Outcome Measure Information:
Title
Objective Response Rate in Phase 1
Description
ORR is defined as the percentage of participants 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 and assessed by an investigator. The denominator in the calculation of the ORR is the number of participants in the full analysis set with measurable disease at baseline.
Time Frame
Up to 49 months
Title
Progression-free Survival
Description
Progression-free survival is defined as the time in months from first dose of study drug until the date of disease progression or death (by any cause in the absence of disease progression) as assessed by RECIST v1.1 by the investigator for Phase 1 and ICR for Phase 2.
Time Frame
Up to 49 months
Title
Disease Control Rate
Description
Disease control rate (DCR) is defined as the percentage of participants with a best overall response of CR or PR or stable disease (SD) recorded at least 24 weeks (± 1 week) after commencement of study drug and prior to any progressive disease (PD) event, as assessed by RECIST v1.1 by the investigator for Phase 1 and ICR for Phase 2.
Time Frame
24 weeks
Title
Duration of Response
Description
Duration of response (DOR) is defined as the time in months from the date of first documented objective response (CR or PR) until the date of documented disease progression or death by any cause in the absence of disease progression as assessed by RECIST v1.1 by the investigator for Phase 1 and ICR for Phase 2.
Time Frame
Up to 49 months
Title
Time to Response
Description
Time to response (TTR) is defined as the time in months from the date of first dose of study drug until the date of first documented objective response as assessed by RECIST v1.1 by the investigator for Phase 1 and ICR for Phase 2.
Time Frame
Up to 49 months
Title
Overall Survival
Description
Overall survival (OS) is defined as the time in months from the date of first dose of study drug until death due to any cause in general.
Time Frame
Up to 49 months
Title
Minor Response Rate
Description
Rate of minor response (or better) is defined as the proportion of participants with a confirmed CR, PR, or minor response (MinR) as assessed by RECIST v1.1 by the investigator for Phase 1 or ICR for Phase 2, where MinR is a reduction from baseline in sum of diameters between 10%-29%. The sum of diameters is defined as per RECIST v1.1 as the sum of longest diameters or short axis of target lesions (mm).
Time Frame
Up to 49 months
Title
Number of Participants With Treatment Dose Interruptions or Reductions
Description
Tolerability of study treatment was assessed by summarizing the number of participants with dose interruptions or reductions that occurred during the treatment period.
Time Frame
Up to 49 months
Title
Area Under the Plasma Concentration-Time Curve (AUC) of Tebentafusp
Description
The AUC was determined in in dose escalation cohorts.
Time Frame
Cycle 1 Day 1 and Cycle 1 Day 15: predose, end of infusion, and 4 and 8 hours postdose
Title
Maximum Plasma Concentration (Cmax) of Tebentafusp
Description
The Cmax is determined in dose escalation cohorts.
Time Frame
Cycle 1 Day 1 and Cycle 1 Day 15: predose, end of infusion, and 4 and 8 hours postdose
Title
Time to Maximum Plasma Concentration (Tmax) of Tebentafusp
Description
The Tmax of tebentafusp is determined in dose escalation cohorts.
Time Frame
Cycle 1 Day 1 and Cycle 1 Day 15: predose, end of infusion, and 4 and 8 hours postdose
Title
Apparent Terminal Plasma Half-life (t½) of Tebentafusp
Description
The t½ of tebentafusp is reported in dose escalation cohorts.
Time Frame
Cycle 1 Day 1 and Cycle 1 Day 15: predose, end of infusion, and 4 and 8 hours postdose
Title
Percentage of Participants With Anti-IMCgp100 Antibody Formation
Description
Overall antidrug antibody (ADA) is presented as number of ADA-positive participants relative to total number of participants with evaluable ADA results in each cohort
Time Frame
Up to 49 months
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Male or female participants 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 participants or participants 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.
Human leukocyte antigen (HLA)-A*0201 positive.
ECOG Performance Status of 0 or 1 at Screening.
Phase 2 will include participants with previously treated uveal melanoma in the metastatic setting.
Exclusion Criteria:
Presence of symptomatic or untreated central nervous system (CNS) metastases, or CNS metastases that require doses of corticosteroids.
History of severe hypersensitivity reactions to other biologic drugs or monoclonal antibodies.
Participants with any out-of-range laboratory values.
Clinically significant cardiac disease or impaired cardiac function.
Active infection requiring systemic antibiotic therapy.
Known history of HIV infection.
Active hepatitis B virus (HBV) or hepatitis C virus (HCV) infection per institutional protocol.
Participants 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.
Any medical condition that would, in the investigator's judgment, prevent participation in the clinical study due to safety concerns, compliance with clinical study procedures or interpretation of study results.
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.
Pregnant, likely to become pregnant, or lactating women.
Facility Information:
Facility Name
University California, San Diego Moores Cancer Center
City
La Jolla
State/Province
California
ZIP/Postal Code
92093
Country
United States
Facility Name
The Angeles Clinic and Research Institute - W LA Office
City
Los Angeles
State/Province
California
ZIP/Postal Code
90025
Country
United States
Facility Name
California Pacific Medical Center
City
San Francisco
State/Province
California
ZIP/Postal Code
94115
Country
United States
Facility Name
University of Colorado Denver Anschutz Medical Campus
City
Aurora
State/Province
Colorado
ZIP/Postal Code
80045
Country
United States
Facility Name
Georgetown University - Lombardi Comprehensive Cancer Center
City
Washington
State/Province
District of Columbia
ZIP/Postal Code
20007
Country
United States
Facility Name
University of Miami Hospital Clinics/Sylvester Comprehensive Cancer Center
City
Miami
State/Province
Florida
ZIP/Postal Code
33136
Country
United States
Facility Name
H. Lee Moffitt Cancer Center and Research Institute, Inc
City
Tampa
State/Province
Florida
ZIP/Postal Code
33612-9497
Country
United States
Facility Name
The University of Chicago Medical Center
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60637
Country
United States
Facility Name
Washington University, School of Medicine
City
Saint Louis
State/Province
Missouri
ZIP/Postal Code
63110
Country
United States
Facility Name
Roswell Park Cancer Institute
City
Buffalo
State/Province
New York
ZIP/Postal Code
14263
Country
United States
Facility Name
Columbia University Medical Center - The New York Presbyterian Hospital
City
New York
State/Province
New York
ZIP/Postal Code
10032
Country
United States
Facility Name
Memorial Sloan Kettering Hospital
City
New York
State/Province
New York
ZIP/Postal Code
10065
Country
United States
Facility Name
Dean A. Mcgee Eye Institute
City
Oklahoma City
State/Province
Oklahoma
ZIP/Postal Code
73104
Country
United States
Facility Name
Providence Portland Medical Center
City
Portland
State/Province
Oregon
ZIP/Postal Code
97213
Country
United States
Facility Name
Thomas Jefferson University Medical Oncology Clinic
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19107
Country
United States
Facility Name
Vanderbilt University Medical Center
City
Nashville
State/Province
Tennessee
ZIP/Postal Code
37232
Country
United States
Facility Name
Baylor Scott & White Health
City
Temple
State/Province
Texas
ZIP/Postal Code
76508
Country
United States
Facility Name
Princess Margaret Cancer Center
City
Toronto
State/Province
Ontario
ZIP/Postal Code
M5G2M9
Country
Canada
Facility Name
Universitaetsklinikum Heidelberg
City
Heidelberg
State/Province
Baden Wuerttemberg
ZIP/Postal Code
69120
Country
Germany
Facility Name
Charite Universitaetsmedizin Berlin - Campus Benjamin Franklin
City
Berlin
ZIP/Postal Code
12200
Country
Germany
Facility Name
ICO l'Hospitalet - Hospital Duran i Reynals
City
L'Hospitalet De Llobregat
State/Province
Barcelona
ZIP/Postal Code
08908
Country
Spain
Facility Name
Hospital Universitario La Paz
City
Madrid
ZIP/Postal Code
28046
Country
Spain
Facility Name
Hospital Universitario Virgen Macarena
City
Sevilla
ZIP/Postal Code
41009
Country
Spain
Facility Name
Hospital General Universitario de Valencia
City
Valencia
ZIP/Postal Code
46014
Country
Spain
Facility Name
The Clatterbridge Cancer Centre
City
Wirral
State/Province
Merseyside
ZIP/Postal Code
CH63 4JY
Country
United Kingdom
Facility Name
Mount Vernon Cancer Centre
City
Northwood
State/Province
Middlesex
ZIP/Postal Code
HA6 2RN
Country
United Kingdom
12. IPD Sharing Statement
Learn more about this trial
A Study of the Intra-Patient Escalation Dosing Regimen With IMCgp100 in Patients With Advanced Uveal Melanoma
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