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

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

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.

Study Overview

• Status: Completed
• Conditions: Uveal Melanoma
• Intervention / Treatment: Drug: IMCgp100

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.

• Study Type: Interventional
• Enrollment (Actual): 146
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• Canada
  • Ontario
    • Toronto, Ontario, Canada, M5G2M9
      • Princess Margaret Cancer Center
• Germany
  • Berlin, Germany, 12200
    • Charite Universitaetsmedizin Berlin - Campus Benjamin Franklin
  • Baden Wuerttemberg
    • Heidelberg, Baden Wuerttemberg, Germany, 69120
      • Universitaetsklinikum Heidelberg
• Spain
  • Madrid, Spain, 28046
    • Hospital Universitario La Paz
  • Sevilla, Spain, 41009
    • Hospital Universitario Virgen Macarena
  • Valencia, Spain, 46014
    • Hospital General Universitario de Valencia
  • Barcelona
    • L'Hospitalet De Llobregat, Barcelona, Spain, 08908
      • ICO l'Hospitalet - Hospital Duran i Reynals
• United Kingdom
  • Merseyside
    • Wirral, Merseyside, United Kingdom, CH63 4JY
      • The Clatterbridge Cancer Centre
  • Middlesex
    • Northwood, Middlesex, United Kingdom, HA6 2RN
      • Mount Vernon Cancer Centre
• United States
  • California
    • La Jolla, California, United States, 92093
      • University California, San Diego Moores Cancer Center
    • Los Angeles, California, United States, 90025
      • The Angeles Clinic and Research Institute - W LA Office
    • San Francisco, California, United States, 94115
      • California Pacific Medical Center
  • Colorado
    • Aurora, Colorado, United States, 80045
      • University of Colorado Denver Anschutz Medical Campus
  • District of Columbia
    • Washington, District of Columbia, United States, 20007
      • Georgetown University - Lombardi Comprehensive Cancer Center
  • Florida
    • Miami, Florida, United States, 33136
      • University of Miami Hospital Clinics/Sylvester Comprehensive Cancer Center
    • Tampa, Florida, United States, 33612-9497
      • H. Lee Moffitt Cancer Center and Research Institute, Inc
  • Illinois
    • Chicago, Illinois, United States, 60637
      • The University of Chicago Medical Center
  • Missouri
    • Saint Louis, Missouri, United States, 63110
      • Washington University, School of Medicine
  • New York
    • Buffalo, New York, United States, 14263
      • Roswell Park Cancer Institute
    • New York, New York, United States, 10032
      • Columbia University Medical Center - The New York Presbyterian Hospital
    • New York, New York, United States, 10065
      • Memorial Sloan Kettering Hospital
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73104
      • Dean A. McGee Eye Institute
  • Oregon
    • Portland, Oregon, United States, 97213
      • Providence Portland Medical Center
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19107
      • Thomas Jefferson University Medical Oncology Clinic
  • Tennessee
    • Nashville, Tennessee, United States, 37232
      • Vanderbilt University Medical Center
  • Texas
    • Temple, Texas, United States, 76508
      • Baylor Scott & White Health

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Dose escalation; Dose escalation cohorts of the intra-patient escalation regimen.	Drug: IMCgp100; Bispecific soluble HLA-A2 restricted gp100-specific T-cell receptor fused to anti-CD3; Other Names: Tebentafusp; Kimmtrak
Experimental: Dose expansion; Dose expansion cohort with the recommended phase 2 dose of the intra-patient dose escalation regimen.	Drug: IMCgp100; Bispecific soluble HLA-A2 restricted gp100-specific T-cell receptor fused to anti-CD3; Other Names: Tebentafusp; Kimmtrak

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
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
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
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
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
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
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
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
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
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
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
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
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

Collaborators and Investigators

• Sponsor: Immunocore Ltd

Study record dates

Study Major Dates

• Study Start (Actual): February 29, 2016
• Primary Completion (Actual): March 20, 2020
• Study Completion (Actual): October 17, 2022

Study Registration Dates

• First Submitted: October 6, 2015
• First Submitted That Met QC Criteria: October 6, 2015
• First Posted (Estimate): October 7, 2015

Study Record Updates

• Last Update Posted (Actual): March 21, 2023
• Last Update Submitted That Met QC Criteria: February 21, 2023
• Last Verified: February 1, 2023

More Information

Terms related to this study

• Keywords: Immunotherapy; ImmTAC; Bispecific T cell receptor fusion protein; metastatic melanoma; IMCgp100; Tebentafusp; gp100; Immune mobilizing monoclonal T cell receptor; against cancer; UM; mUM; Kimmtrak
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Eye Diseases; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Uveal Diseases; Neuroendocrine Tumors; Nevi and Melanomas; Eye Neoplasms; Melanoma; Uveal Neoplasms
• Other Study ID Numbers: IMCgp100-102

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes