Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02570308
Recruitment Status : Active, not recruiting
First Posted : October 7, 2015
Last Update Posted : April 9, 2021
Sponsor:
Information provided by (Responsible Party):
Immunocore Ltd

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

Detailed Description:

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.

Layout table for study information
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
Actual Primary Completion Date : June 30, 2020
Estimated Study Completion Date : September 20, 2021


Arm Intervention/treatment
Experimental: Dose escalation
Dose escalation cohorts of the intra-patient escalation regimen. This arm is closed
Drug: IMCgp100
Bispecific soluble HLA-A2 restricted gp100-specific TCR fused to anti-CD3

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 TCR fused to anti-CD3




Primary Outcome Measures :
  1. Phase 1 Recommended phase 2 dose of the intra-patient escalation regimen (RP2D-IE) [ Time Frame: 1 years ]
  2. 2. Phase 2: Objective response rate by RECIST 1.1 assessed by independent central review [ Time Frame: 2 years ]

Secondary Outcome Measures :
  1. Objective response rate (Phase 1) [ Time Frame: 2 years ]
  2. Progression free survival [ Time Frame: 2 years ]
  3. Overall survival [ Time Frame: 2 years ]
  4. Duration of response [ Time Frame: 2 years ]
  5. Time to response [ Time Frame: 2 years ]
  6. Minor response rate [ Time Frame: 2 years ]
  7. Number of treatment dose interruptions and reductions [ Time Frame: 2 years ]
  8. Area under the plasma concentration-time curve (AUC) [ Time Frame: 2 years ]
  9. Area under the plasma concentration-time curve (AUC) [ Time Frame: 3 weeks ]
  10. The maximum observed plasma drug concentration after single dose administration (Cmax) [ Time Frame: 2 years ]
  11. The time to reach maximum plasma concentration (Tmax) [ Time Frame: 3 weeks ]
  12. The elimination half-life (t1/2) [ Time Frame: 3 weeks ]
  13. Incidence of anti-IMCgp100 antibody formation [ Time Frame: 2 years ]


Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Male or female patients 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 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
  5. Human leukocyte antigen (HLA)-A*0201 positive
  6. ECOG Performance Status of 0 or 1 at Screening
  7. Patients in Phase 2 will include patients 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. Patient 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. 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
  9. Malignant disease, other than that being treated in this study.
  10. 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
  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.

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 Show 26 study locations
Sponsors and Collaborators
Immunocore Ltd
Layout table for additonal information
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 9, 2021
Last Verified: April 2021
Keywords provided by Immunocore Ltd:
Tebentafusp
IMCgp100
gp100
metastatic melanoma
ImmTAC
Immunotherapy
Bispecific T cell receptor fusion protein
Immune mobilizing monoclonal T cell receptor
against cancer
UM
mUM
Additional relevant MeSH terms:
Layout table for MeSH terms
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