Clinical trial NCT02570308: 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
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: 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
Lead sponsor: Immunocore Ltd
Sponsor class: INDUSTRY
First posted: 2015-10-07
Enrollment: 146
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Eligibility criteria: Inclusion Criteria:

1. Male or female participants 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 uveal melanoma (mUM).
4. 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.
5. Human leukocyte antigen (HLA)-A\*0201 positive.
6. ECOG Performance Status of 0 or 1 at Screening.
7. Phase 2 will include participants with previously treated uveal melanoma in the metastatic setting.

Exclusion Criteria:

1. Presence of symptomatic or untreated central nervous system (CNS) metastases, or CNS metastases that require doses of corticosteroids.
2. History of severe hypersensitivity reactions to other biologic drugs or monoclonal antibodies.
3. Participants with any out-of-range laboratory values.
4. Clinically significant cardiac disease or impaired cardiac function.
5. Active infection requiring systemic antibiotic therapy.
6. Known history of HIV infection.
7. Active hepatitis B virus (HBV) or hepatitis C virus (HCV) infection per institutional protocol.
8. 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.
9. Malignant disease, other than that being treated in this study.
10. 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.
11. 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.
12. Pregnant, likely to become pregnant, or lactating women.

Primary outcomes:
measure: Number of Participants With a Dose Limiting Toxicity (DLT) in Phase 1
timeFrame: Up to 49 months
measure: Objective Response Rate in Phase 2
timeFrame: Up to 38 months
Secondary outcomes:
measure: Objective Response Rate in Phase 1
timeFrame: Up to 49 months
measure: Progression-free Survival
timeFrame: Up to 49 months
measure: Disease Control Rate
timeFrame: 24 weeks
measure: Duration of Response
timeFrame: Up to 49 months
measure: Time to Response
timeFrame: Up to 49 months
measure: Overall Survival
timeFrame: Up to 49 months
measure: Minor Response Rate
timeFrame: Up to 49 months
measure: Number of Participants With Treatment Dose Interruptions or Reductions
timeFrame: Up to 49 months
measure: Area Under the Plasma Concentration-Time Curve (AUC) of Tebentafusp
timeFrame: Cycle 1 Day 1 and Cycle 1 Day 15: predose, end of infusion, and 4 and 8 hours postdose
measure: Maximum Plasma Concentration (Cmax) of Tebentafusp
timeFrame: Cycle 1 Day 1 and Cycle 1 Day 15: predose, end of infusion, and 4 and 8 hours postdose
measure: Time to Maximum Plasma Concentration (Tmax) of Tebentafusp
timeFrame: Cycle 1 Day 1 and Cycle 1 Day 15: predose, end of infusion, and 4 and 8 hours postdose
measure: Apparent Terminal Plasma Half-life (t½) of Tebentafusp
timeFrame: Cycle 1 Day 1 and Cycle 1 Day 15: predose, end of infusion, and 4 and 8 hours postdose
measure: Percentage of Participants With Anti-IMCgp100 Antibody Formation
timeFrame: Up to 49 months
Other outcomes:
Locations:
city: La Jolla
country: United States
facility: University California, San Diego Moores Cancer Center
state: California
city: Los Angeles
country: United States
facility: The Angeles Clinic and Research Institute - W LA Office
state: California
city: San Francisco
country: United States
facility: California Pacific Medical Center
state: California
city: Aurora
country: United States
facility: University of Colorado Denver Anschutz Medical Campus
state: Colorado
city: Washington
country: United States
facility: Georgetown University - Lombardi Comprehensive Cancer Center
state: District of Columbia
city: Miami
country: United States
facility: University of Miami Hospital Clinics/Sylvester Comprehensive Cancer Center
state: Florida
city: Tampa
country: United States
facility: H. Lee Moffitt Cancer Center and Research Institute, Inc
state: Florida
city: Chicago
country: United States
facility: The University of Chicago Medical Center
state: Illinois
city: Saint Louis
country: United States
facility: Washington University, School of Medicine
state: Missouri
city: Buffalo
country: United States
facility: Roswell Park Cancer Institute
state: New York
city: New York
country: United States
facility: Columbia University Medical Center - The New York Presbyterian Hospital
state: New York
city: New York
country: United States
facility: Memorial Sloan Kettering Hospital
state: New York
city: Oklahoma City
country: United States
facility: Dean A. Mcgee Eye Institute
state: Oklahoma
city: Portland
country: United States
facility: Providence Portland Medical Center
state: Oregon
city: Philadelphia
country: United States
facility: Thomas Jefferson University Medical Oncology Clinic
state: Pennsylvania
city: Nashville
country: United States
facility: Vanderbilt University Medical Center
state: Tennessee
city: Temple
country: United States
facility: Baylor Scott & White Health
state: Texas
city: Toronto
country: Canada
facility: Princess Margaret Cancer Center
state: Ontario
city: Heidelberg
country: Germany
facility: Universitaetsklinikum Heidelberg
state: Baden Wuerttemberg
city: Berlin
country: Germany
facility: Charite Universitaetsmedizin Berlin - Campus Benjamin Franklin
city: L'Hospitalet De Llobregat
country: Spain
facility: ICO l'Hospitalet - Hospital Duran i Reynals
state: Barcelona
city: Madrid
country: Spain
facility: Hospital Universitario La Paz
city: Sevilla
country: Spain
facility: Hospital Universitario Virgen Macarena
city: Valencia
country: Spain
facility: Hospital General Universitario de Valencia
city: Wirral
country: United Kingdom
facility: The Clatterbridge Cancer Centre
state: Merseyside
city: Northwood
country: United Kingdom
facility: Mount Vernon Cancer Centre
state: Middlesex
Study officials:
References: