A Study of the Intra-Patient Escalation Dosing Regimen With IMCgp100 in Patients With Advanced Uveal Melanoma

Uveal Melanoma Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02570308
• Other study ID #: IMCgp100-102
• Status: Completed
• Phase: Phase 1/Phase 2
• Start date: February 29, 2016
• Est. completion date: October 17, 2022

Study information

• Verified date: February 2023
• Source: Immunocore Ltd
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 146
• Est. completion date: October 17, 2022
• Est. primary completion date: March 20, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Melanoma
• Uveal Melanoma
• Uveal Neoplasms

Intervention

Drug:
• IMCgp100
Bispecific soluble HLA-A2 restricted gp100-specific T-cell receptor fused to anti-CD3

Locations

Country	Name	City	State
Canada	Princess Margaret Cancer Center	Toronto	Ontario
Germany	Charite Universitaetsmedizin Berlin - Campus Benjamin Franklin	Berlin
Germany	Universitaetsklinikum Heidelberg	Heidelberg	Baden Wuerttemberg
Spain	ICO l'Hospitalet - Hospital Duran i Reynals	L'Hospitalet De Llobregat	Barcelona
Spain	Hospital Universitario La Paz	Madrid
Spain	Hospital Universitario Virgen Macarena	Sevilla
Spain	Hospital General Universitario de Valencia	Valencia
United Kingdom	Mount Vernon Cancer Centre	Northwood	Middlesex
United Kingdom	The Clatterbridge Cancer Centre	Wirral	Merseyside
United States	University of Colorado Denver Anschutz Medical Campus	Aurora	Colorado
United States	Roswell Park Cancer Institute	Buffalo	New York
United States	The University of Chicago Medical Center	Chicago	Illinois
United States	University California, San Diego Moores Cancer Center	La Jolla	California
United States	The Angeles Clinic and Research Institute - W LA Office	Los Angeles	California
United States	University of Miami Hospital Clinics/Sylvester Comprehensive Cancer Center	Miami	Florida
United States	Vanderbilt University Medical Center	Nashville	Tennessee
United States	Columbia University Medical Center - The New York Presbyterian Hospital	New York	New York
United States	Memorial Sloan Kettering Hospital	New York	New York
United States	Dean A. Mcgee Eye Institute	Oklahoma City	Oklahoma
United States	Thomas Jefferson University Medical Oncology Clinic	Philadelphia	Pennsylvania
United States	Providence Portland Medical Center	Portland	Oregon
United States	Washington University, School of Medicine	Saint Louis	Missouri
United States	California Pacific Medical Center	San Francisco	California
United States	H. Lee Moffitt Cancer Center and Research Institute, Inc	Tampa	Florida
United States	Baylor Scott & White Health	Temple	Texas
United States	Georgetown University - Lombardi Comprehensive Cancer Center	Washington	District of Columbia

Sponsors (1)

Lead Sponsor	Collaborator
Immunocore Ltd

Countries where clinical trial is conducted

United States,  Canada,  Germany,  Spain,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	Up to 49 months
Primary	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.	Up to 38 months
Secondary	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.	Up to 49 months
Secondary	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.	Up to 49 months
Secondary	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.	24 weeks
Secondary	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.	Up to 49 months
Secondary	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.	Up to 49 months
Secondary	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.	Up to 49 months
Secondary	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).	Up to 49 months
Secondary	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.	Up to 49 months
Secondary	Area Under the Plasma Concentration-Time Curve (AUC) of Tebentafusp	The AUC was determined in in dose escalation cohorts.	Cycle 1 Day 1 and Cycle 1 Day 15: predose, end of infusion, and 4 and 8 hours postdose
Secondary	Maximum Plasma Concentration (Cmax) of Tebentafusp	The Cmax is determined in dose escalation cohorts.	Cycle 1 Day 1 and Cycle 1 Day 15: predose, end of infusion, and 4 and 8 hours postdose
Secondary	Time to Maximum Plasma Concentration (Tmax) of Tebentafusp	The Tmax of tebentafusp is determined in dose escalation cohorts.	Cycle 1 Day 1 and Cycle 1 Day 15: predose, end of infusion, and 4 and 8 hours postdose
Secondary	Apparent Terminal Plasma Half-life (t½) of Tebentafusp	The t½ of tebentafusp is reported in dose escalation cohorts.	Cycle 1 Day 1 and Cycle 1 Day 15: predose, end of infusion, and 4 and 8 hours postdose
Secondary	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	Up to 49 months